bluuebunny/crossref_metadata_2025 huggingface dataset:
Expressive semantic deficit in the productive language of males with fragile X syndrome
Authors: Sudhalter Vicki , Maranion Maria , Brooks Patricia
Published: June 2005

Eleven males with fragile X syndrome [fra(X)] between the ages of 6 and 41, with an average communication age of 4 years 4 months and 11 normally developing 4 year old boys were administered a sentence completion task that assessed expressive semantic competence. The fra(X) males produced significantly more semantic errors than the normally developing 4 year children. Additionally, it was shown that sentences which could be correctly completed by a wider choice of words affected fra(X) males more than the nondisabled children. These 2 results suggests that the expressive semantic system is an area of specific deficit in fra(X) males.
Verbal learning and memory among heterozygous fragile X females
Authors: Grigsby Jim , Kemper Melinda B. , Hagerman Randi J.
Published: June 2005

In this paper we report the results of a brief examination of verbal learning and memory in 20 heterozygous fragile X [fra(X)] positive females and in 2 control groups of 20 subjects each. One control group was composed of fra(X)‐negative mothers (obligate carriers) and sisters of male probands with fra(X) syndrome, while the other consisted of 14 head injured and 6 learning disabled females. Intellectual functioning was assessed by means of the Wechsler scales, and learning was assessed by several different clinical memory tests. Significant differences were found between groups on measures of short‐term memory and learning efficiency. Groups did not differ on measures of cued recall or delayed recall. The findings are consistent with other data and suggest the possibility that central information processing and/or specific encoding processes are defective in persons with fra(X).
Fra(X) prenatal diagnosis: Are endoreduplicated and polyploid cells useful diagnostic criteria?
Authors: Krawczun Michael S. , Duncan Charlotte J. , Stark‐Houck Sandra L. , Jenkins Edmund C.
Published: June 2005

Cytogenetic and molecular protocols for prenatal ascertainment of the fragile X syndrome and the associated fragile site at Xq27.3 are relatively reliable. Any new diagnostic method which becomes available still elicits much interest. Kimchi‐Sarfaty et al. [1991] reported an increase in frequency of endoreduplication and polyploidy in fra(X) lymphoblasts and amniocytes when cultured with methotrexate (MTX) or fluorodeoxyuridine. Recently we analyzed the endoreduplication/polyploidy system using amniotic fluid, chorionic villus, and fibroblasts from fra(X) positive abortus cell cultures and from control samples. We observed no increased expression of endoreduplicated or polyploid cells in fra(X) positive amniocytes after exposure to MTX. The data presented here clearly dispute the value of endoreduplication/polyploid scoring as a diagnostic aid in prenatal fra(X) analysis.
Recent experience in prenatal diagnosis of fragile X
Authors: Howard‐Peebles Patricia N. , Maddalena Anne
Published: June 2005

Our experience with 48 prenatal fragile X cases (35 amniocenteses; 13 chorionic villi samplings) is summarized. Of these 48 cases, 18 consultands were known to be carriers of fragile X. No cytogenetic false negatives or positives were identified but 2 cases were uninterpretable. Cytogenetic recommendations include: 1) Ten or more days recovery time after growth in Chang medium, and 2) use of 3‐4 media/inducer systems with duplicate harvests. Direct DNA probe testing will likely be the method of choice for prenatal diagnosis after sufficient data are collected to verify interpretation. Until then, both cytogenetic and direct DNA techniques should be utilized.
Prenatal diagnosis and carrier detection in fragile X
Authors: Von Koskull Harriet , Nordström Ann‐Marie , Salonen Riitta , Peltonen Leena
Published: June 2005

Prenatal diagnosis was performed in 81 cases at risk for the fragile X syndrome. There were 12 fra (X)‐positive cases, two of which showed low expression in cultured amniotic fluid cells. FUdR and high thymidine were used for induction of fra(X) (q27.3) expression in all cases. In 21 cases linkage studies were performed, 7 with probes for the loci DXS52, DXS98 and DXS105, 13 with probes for DXS369 and DXS296, DXS304 or DXS374 and one with the probe Do33 for DXS465. In 11 of these cases linkage analysis gave risk figures higher than 95% or lower than 5%, all in concordance with the cytogenetic findings. Discordance was found in three cases studied earlier, the two cases with low expression mentioned above and one cytogenetically normal case, which were now restudied with the new probes. RFLP‐studies and linkage analysis was also performed for 24 cytogenetically fra(X)‐negative females having a 50%, 25% or 12.5% risk of being carriers according to pedigree data. In 15 cases the risk dropped to 1% or less. Six of these women were pregnant and had asked for prenatal diagnosis but after genetic counseling prenatal diagnosis was avoided.
Limited size of the fragile X site shown by fluorescence in situ hybridization
Authors: Verkerk Annemieke J. M. H. , Eussen Bert H. J. , Van Hemel Jan O. , Oostra Ben A.
Published: June 2005

Cosmids, isolated from a 475 kb YAC that spans the fragile X region, and the YAC itself, were used for fluorescence in situ hybridization (FISH) on metaphase chromosomes from fragile X patients. Cosmid 22.3, containing most of the hybrid translocation breakpoints, shows in situ hybridization signals distal and proximal from the fragile X site. We propose that the size of the fragile site is limited to 20 kb.
On some technical aspects of direct DNA diagnosis of the fragile X syndrome
Authors: Rousseau F. , Heitz D. , Biancalana V. , Oberlé I. , Mandel J. L.
Published: June 2005

Direct DNA analysis of fragile X [Fra (X)] mutations has already shown its clear superiority for postnatal and prenatal diagnosis of the disorder and for carrier detection. However, it is of great importance to have conditions which gurantee optimal reliability and sensitivity. Some mutations may be more difficult to detect, especially in female carriers: this is the case for small amplifications of the CGG repeat (premutations) or for smears which can be generated by the instability of the full mutation in somatic tissues. We present the various alternatives (probe/enzymes combinations) for Southern blot based diagnosis, the possible artefacts and our detailed experimental protocol, which has given excellent results on a large number of families. While detection of amplification, using for instance EcoRI, appears sufficient for initial testing of mentally retarded patients, once the fra(X) diagnosis has been established, we favor the use of an EcoRI +EagI digest, which detects both amplification and abnormal methylation, for analysis of the family, including carrier detection and prenatal diagnosis. We discuss the place of proposed PCR based techniques for detection of mutations, or for indirect tracking using polymorphic microsatellites in the immediate vicinity of the fra(X) locus.
Two families with Xq27.3 fragility, no detectable insert in the FMR‐1 gene, mild mental impairment, and absence of the Martin‐Bell phenotype
Authors: Dennis Nicholas R. , Curtis Greta , Macpherson James N. , Jacobs Patricia A.
Published: June 2005

In 2 families, propositi were investigated because of mild developmental delay and, in one case, behavior disorders. Seven males in the 2 families were found to have a fragile site at Xq27.3 but the usual insert in the FMR‐1 gene was absent. The affected males had mild, or in some cases, no clear intellectual impairment and did not have the Martin‐Bell phenotype. Carrier females in one family tended to show a high level of cytogenetic expression of the fragile site but were clinically normal.

It is not yet clear whether these families have unusual mutations in the FMR‐1 gene or whether their fragile sites are different, but cytogenetically indistinguishable from, that associated with inserts in the FMR‐1 gene.
Parental origin of the Fra(X) gene is a major determinant of the cytogenetic expression and the CGG repeat length in female carriers
Authors: Smits Arie , Smeets Dominique , Dreesen Jos , Hamel Ben , de Haan Anton , van Oost Bernard
Published: June 2005

The fragile X [fra(X)] syndrome is the most frequent form of inherited mental retardation, and co‐segregates with a fragile site at Xq27.3 as well as with insertion of a variable number of trinucleotide repeats in the 5′‐end of the FMR‐1 gene. As the fra(X) gene is transmitted by females as well as males, we have investigated whether the parental origin of the fra(X) gene has an effect upon the cytogenetic expression and CGG repeat length. An increased fragment length of 0.2 ‐ 0.6 kb appeared to be associated with a very low expression or even complete absence of the fragile site as well as with a normal phenotype, and was seen mostly in cases of paternal inheritance. However, in most female carriers with the maternally inherited fra(X) gene we found dispersed fragments ranging from 1.4 ‐ 6.5 kb or even complete absence of a hybridization signal. Within the group of female carriers with the maternally inherited fra(X) gene we found a statistically significant correlation between the level of the cytogenetic expression and the PstI restriction fragment length encompassing the CGG repeat. These data can be taken as indirect evidence that CGG repeat length and cytogenetic expression are causally related.
Direct DNA analysis of fragile X syndrome in Spanish pedigrees
Authors: Tejada Isabel , Mornet Etienne , Biancalana Valérie , Oberlé Isabelle , Boué Joelle , Mandel Jean‐Louis , Boué André
Published: June 2005

Eleven complete Spanish pedigrees with fragile X syndrome were analysed by Southern blotting with the DNA probe StB 12.3 previously isolated and described by Oberlé et al. [1991]. This probe allowed the direct detection of affected males and carrier females and was able to distinguish between normal males and normal transmitting males (NTMs). One hundred and twenty three individuals were analyzed, 115 from the pedigrees and 8 from the general population. Five mosaic cases were found (4 males and one female) showing both the premutation and the full mutation. One half of the females with the full mutation were mentally retarded but no female with mental retardation carried the premutated pattern, suggesting that the absence of the full mutation in females is a very good criterion for pre‐or postnatal diagnosis of normal mental status.
Fragile X mental retardation and the iduronate sulphatase locus: Testing laird's model of Fra(X) inheritance
Authors: Clarke A. , Bradley D. , Gillespie K. , Rees D. , Holland A. , Thomas N. S. T.
Published: June 2005

Fragile X [fra(X)] mental retardation syndrome is the most frequent familial cause of mental handicap. The clinical phenotype is associated with a rare fragile site at Xq27.3. The mutation underlying the disorder, an insertion into the FMR‐1 gene, has been characterized, but the pathogenesis of the condition is obscure and the pattern of inheritance is still not fully understood.

One model of fra(X) pathogenesis was proposed by Laird in 1987, suggesting that the fra(X) mutation acts as a cis‐acting, local block to the pre‐oogenesis reactivation of the inactivated X chromosome. To test this model, we examined the activity of the F8, F9 and iduronate sulphatase (IDS) loci.

The level of IDS in the serum of fra(X) males was found to be very significantly reduced in the fra(X) group when compared to that of control males: this lends support to Laird's model of fra(X) pathogenesis. However, we detected no methylation differences between fra(X) and control samples at the IDS locus, although such changes are known in fra(X) males at sites closer to the fragile site. Thus the mechanism of the reduction in IDS activity has not been identified.
Fragile X screening program in a spanish region
Authors: Gabarrón Joaquina , Lopez Isabel , Glover Guillermo , Carbonell Pablo
Published: June 2005

In a Spanish region with a population of one million, we screened 371 mentally retarded males, who had no previous diagnosis for fragile X [fra(X))] syndrome. Fifty‐three of the 371 males were fra(X) positive. Of these 44 of 362 or 12.1% were unrelated. Family studies identified a large number of obligate carriers and women at risk for being carriers who were given genetic counseling including prenatal diagnostic information. Considering the age of the carriers and the fertility rate, 23 affected males could be born to these women. The prevention potential of this program suggests that it is highly cost‐effective.
Nomenclature guidelines for X‐linked mental retardation
Authors: Mulley J. C. , Kerr B. , Stevenson R. , Lubs H.
Published: June 2005

Nomenclature guidelines are proposed for non‐specific and for syndromal forms of X‐linked mental retardation. Non‐specific mental retardations (MRX) are given unique symbols for each family (MRX1, MRX2, MRX3 …). Syndromal mental retardations (MRXS) which do not as yet have specific symbols are given unique interim symbols for each syndrome (MRXS1, MRXS2, MRXS3 …). The prerequisite for assignment of serial MRX and MRXS gene symbols is a minimum lod score (or multipoint lod score) of +2 between the MR locus and one or more X chromosome markers. Prior approval of availability for proposed gene symbols must be obtained from the Nomenclature Committee of the Human Gene Mapping Workshops.
MASA syndrome: Delineation of the clinical spectrum at prepubertal age
Authors: Fryns J. P. , Schrander‐Stumpel C. , De Die‐Smulders C. , Borghgraef M. , Van Den Berghe H.
Published: June 2005

Here we describe the clinical and neurological findings in 2 brothers with MASA syndrome and the changes in phenotypic and neurological findings during the prepubertal period.

MASA syndrome seems to be an X‐linked mental retardation syndrome with progressively appearing manifestations and neurological signs, making clinical diagnosis before age 4 years difficult.
Linkage of nonspecific X‐linked mental retardation to Xq21.31
Authors: Jedele Kerry B. , Michels Virginia V. , Schaid Daniel J. , Schowalter Karen V. , Thibodeau Stephen N.
Published: June 2005

Mental retardation unassociated with the Fragile X syndrome accounts for up to 60% of patients with X‐linked mental retardation. In this investigation, we report on a family with mild non‐specific X‐linked mental retardation (MRX) without other apparent phenotypic abnormalities. Linkage analysis on 27 relatives using 18 polymorphic markers spanning the X‐chromosome demonstrated close linkage to DXYS1 with a peak LOD score of 2.14 at a θ of 0. Numerous families with various types of MRX have now been studied by other investigators using molecular genetic techniques. In addition to the family described in this report, a number of these have demonstrated linkage to the DXYS1 locus. These data suggest that a gene for mental retardation may exist in the region of DXYS1. Alternatively, this area of the X‐chromosome may harbor multiple different but closely linked genes which cause the various types of MRX.
New XLMR syndrome with characteristic face, hypogenitalism, congenital hypotonia and pachygyria
Authors: Zollino M. , Mastroiacovo P. , Zampino G. , Mariotti P. , Neri G.
Published: June 2005

A previously unreported X‐linked MCA/MR syndrome is described in 4 members of a large family. Phenotypic manifestations include mental retardation, microcephaly, failure to thrive, severe congenital hypotonia, characteristic face, hypogenitalism, pachygyria. This appears to be an X‐linked dominant trait with decreased penetrance and expressivity in carrier females.
Spastic paraplegia with iron deposits in the basal ganglia: A new X‐linked mental retardation syndrome
Authors: Arena J. Fernando , Schwartz Charles , Stevenson Roger , Lawrence Laura , Carpenter Anna , Duara Ranjan , Ledbetter David , Huang Tim , Lehner Thomas , Ott Jurg , Lubs Herbert A.
Published: June 2005

We report on a family with X‐linked mental retardation (XLMR) and severe spastic paraplegia. Appearance is normal but there is severe involvement of the lower limbs (affected relatives never walked), with minimal involvement of the upper limbs and unusual MRI findings including macrogyria, white matter hypoplasia, lack of myelination and a markedly increased paramagnetic signal suggestive of iron deposition. Linkage studies documented possible linkage, with no recombination, between the disease locus and DXS424. A 7‐point linkage analysis yielded a maximum LOD score of 1.9, (θ=0.00) for three loci spanning Xq22‐q25. The combination of the unusual clinical and MRI findings and the tentative localization to a region different than other XLMR syndromes with spastic paraplegia, provide good evidence that this is a new XLMR syndrome.
Allan‐herndon‐dudley syndrome: Clinical and linkage studies on a second family
Authors: Bialer Martin G. , Lawrence Laura , Stevenson Roger E. , Silverberg Gittel , Williams Marjorie K. , Arena J. Fernando , Lubs Herbert A. , Schwartz Charles E.
Published: June 2005

We restudied a family with X‐linked mental retardation (XLMR) originally reported in abstract form by Davis et al. [1981]. All 8 living affected males were examined. Characteristics included severe mental retardation, spastic paraplegia, dysarthria, muscle wasting, scoliosis, broad shallow pectus excavatum, long face, large ears with minor modeling anomalies, foot deformities, joint contractures, and neck drop. Stature, OFC, testicular volume, high resolution chromosome and fragile X studies, and plasma amino acids were all normal. Their manifestations closely resemble those of a large family with XLMR originally reported by Allan et al. [1944] and restudied by Stevenson et al. [1990]. This condition has been termed the Allan‐Herndon‐Dudley syndrome (AHDS). As AHDS has been mapped to Xq21, mapping studies were undertaken to determine if this family maps to the same location. These studies demonstrate tight linkage to Xq21, with a maximum lod score of 2.88 obtained with probe pX65H7 (DXS72). Multipoint analysis located the mutant gene quite close to pX65H7 (multipoint Z=4.14), slightly more proximal in Xq21 than was suggested by the data from the original AHDS family. It appears likely that this family is the second reported family with AHDS.
Monosomy 18q 12.1→21.1: A recognizable aneuploidy syndrome? Report of a patient and review of the literature
Authors: Krasikov Natalie , Thompson Kate , Sekhon Gurbax Singh
Published: June 2005

This report of a patient with an interstitial deletion 18q and review of previously described cases suggest a clinically recognizable syndrome. The phenotype appears to result from a microdeletion of part of 18q12.2 or q12.3, or a deletion of parts of both bands. © 1992 Wiley‐Liss, Inc.
Recognizable behavioral and somatic phenotype in patients with proximal interstitial 18q deletion: Report on a new affected child and follow‐up on the original reported familial cases
Authors: Chudley Albert E. , Kovnats Sylvia , Ray Manoranjan
Published: June 2005

We describe a moderately retarded boy with a chromosome 18 deletion involving the regions q11.2q12.2. His phenotype is similar to that of other reported cases of proximal interstitial deletions involving 18q. We also provide follow‐up information on the first 4 cases of proximal interstitial deletion of 18q from a family with a complex chromosome rearrangement originally reported in 1974. © 1992 Wiley‐Liss, Inc.
Endocardial cushion defect: Further studies of “isolated” versus “syndromic” occurrence
Authors: Carmi Rivka , Boughman Joann A. , Ferencz Charlotte
Published: June 2005

The isolated occurrence of endocardial cushion defect (ECD) has been suggested to differ from its occurrence within the context of a syndrome, with regard to the nature (complete or partial) of the defect and the associated cardiovascular malformations. Analysis of data derived from the Baltimore‐Washington Infant Study of congenital cardiovascular malformations supports the observation that “syndromic” ECD tends to be of the complete atrioventricular canal type and is less frequently associated with left cardiac anomalies than the isolated form. However, each syndrome has a unique impact on the overall cardiovascular “phenotype,” including the ECD. This is especially true for Down and Ivemark syndromes, which are most frequently associated with ECD, but also for other syndromes as well. It is also suggested that isolated ECD is specifically associated with gastrointestinal and urinary tract anomalies. However, in Down syndrome ECD appears to be a specific cardiovascular expression of the trisomic state that is unrelated to other noncardiac malformations. Additional information on the association of ECD with other less common genetic syndromes is needed in order to further investigate the possible genetic basis of this cardiac defect. © 1992 Wiley‐Liss, Inc.
Ring chromosome 20 and possible assignment of the structural gene encoding human carboxypeptidase‐L to the distal segment of the long arm of chromosome 20
Authors: Halal Fahed , Chitayat David , Parikh Hasu , Rosenblatt Bernard , Tranchemontagne Julie , Vekemans Michel , Potier Michel
Published: June 2005

We report on a 14‐year‐old boy with ring chromosome 20. Clinical manifestations included postnatal growth retardation, epilepsy, microcephaly, behaviour disorder, minor facial anomalies, small sella turcica, possible partial growth hormone deficiency, and mental retardation. A decreased activity of enzyme carboxypeptidase‐L/ protective protein (CP/PP) in cultured fibroblasts was demonstrated in our patient and a patient with a karyotype 46,XY,−14,+der(14)t(14;20)(14pter→14q32.3::20q13.1→20qter)mat. This suggests possible assignment of the CP/PP gene to the distal segment of 20q. © 1992 Wiley‐Liss, Inc.
Trisomy 16p in a liveborn offspring due to maternal translocation t(16;21)(q11;p11) and review of the literature
Authors: Léonard Claude , Huret Jean Loup , Imbert Marie‐Claude , Lebouc Yves , Selva Jacqueline , Boulley Anne‐Marie
Published: June 2005

We report on a case of dup(16p) and review previous cases. The triplicated chromosome region leading to this specific syndrome lies in 16p13.1 p13.3. Most of the cases are inherited and the mode of segregation was found to be 3:1 in half of the cases, but these observations might be due to biases. The other chromosomes involved in the translocations as well as the breakpoints in these chromosomes do not appear to be random. © 1992 Wiley‐Liss, Inc.
New variant in exon 3 of the proteolipid protein (PLP) gene in a family with pelizaeus‐merzbacher disease
Authors: Pratt Victoria M. , Trofatter James A. , Larsen Marianne B. , Hodes M. E. , Dlouhy Stephen R.
Published: June 2005

A C → G transversion has been found in exon 3 of the PLP gene of affected males and their mother in a single sibship with Pelizaeus‐Merzbacher disease (PMD). The transversion should not result in an amino acid change in the protein but it does result in the loss of a HaeIII restriction endonuclease cleavage site. It is concordant with the disease in this family. One‐hundred‐ten unrelated X chromosomes are negative for this mutation. No other sequence defect was found in the PLP exons of the affected males. The cause of disease in this family remains unknown, but the association between this rare mutation and PMD is intriguing. The mutation can serve as a marker for following segregation of the PLP gene.
Bilateral anophthalmia, esophageal atresia, and right cryptorchidism: A new entity?
Authors: Arroyo Ignacio , García María Jesús , Cimadevilla Carmen Eloína , Carretero Valentín , Bermejo Eva , Martínez‐Frías María Luisa
Published: June 2005

We report on a child with bilateral anophthalmia, esophageal atresia, and cryptorchidism. This is the first case observed in the Spanish Collaborative Study of Congenital Malformations (ECEMC) with this constellation of congenital anomalies, and it is similar to that described in 1988 by Rogers. We think that it may constitute a new syndrome. © 1992 Wiley‐Liss, Inc.
Trisomy 9: An additional case with unique manifestations
Authors: de Michelena María I. , Sánchez Raul , Muñoz Pedro , Cabello Emilio , Rojas Pablo , de Olazaval Eduardo
Published: June 2005

We report on an infant with multiple congenital anomalies and mosaic trisomy 9. Clinical findings are presented, and compared with those of the 24 cases previously reported. Some unusual characteristics found in this patient include macrocephaly, an extreme degree of palatal hypoplasia, and abnormally shaped long bones. © 1992 Wiley‐Liss, Inc.
Interstitial deletion of 10q: Clinical features and literature review
Authors: Lobo Sandra , Cervenka Jaroslav , London Arnold , Pierpont Mary Ella M.
Published: June 2005

We report on a patient with interstitial deletion of 10q and compare her to 8 previously described patients, 2 of whom have chromosomal breakpoints similar to our patient. Minor anomalies including broad forehead, hypertelorism, strabismus, prominent philtrum, and “dysplastic” pinnae are present in our patient. Psychomotor retardation and hypotonia are universal findings in 10q interstitial deletion. Growth retardation, not present in our patient, is seen in some. These clinical findings are sufficiently distinct to suggest early chromosome studies. © 1992 Wiley‐Liss, Inc.
Paraplegia and congenital contractures as a consequence of intrauterine trauma
Authors: Weyerts Leah K. , Jones Marilyn C. , James Hector E.
Published: June 2005

We present a newborn infant with paraplegia and contractures of the lower limbs, consistent with neurologic injury rather than malformation. The mother was involved in a severe motor vehicle accident during the sixth month of pregnancy. We propose that this infant's injuries are a result of that accident. © 1992 Wiley‐Liss, Inc.
Trisomy 18 and a constitutional maternal translocation (2;18)
Authors: Teshima Ikuko E. , Winsor Elizabeth J. T. , Van Allen Margot I.
Published: June 2005

Parental chromosomes are usually not analyzed in cases of trisomy 18 because the extra 18 is assumed to have arisen through a meiotic nondisjunctional event. We report on a case of a trisomy 18 and a maternal translocation (2;18)(q34;q12). © 1992 Wiley‐Liss, Inc.
Poland anomaly with a limb body wall disruption defect: Case report and review
Authors: Bamforth J. Stephen , Fabian Clifford , Machin Geoffrey , Honore Louis
Published: June 2005

We describe a female infant with apparent Poland anomaly (PA) and limb body wall defect.

Analysis of the defects suggest that a disruption of the lateral embryonic plate mesoderm may have been responsible for the observed lesions. Because of the overlap of this case with PA, we re‐examined previous reports of this syndrome. We think that the lesions could be equally well explained as a mesodermal disruption, and point out a previously unrecognised discrepancy between sex and affected side in sporadic PA and inherited PA which supports this view. © 1992 Wiley‐Liss, Inc.
Autosomal recessive acrorenal syndrome
Authors: Miltényi Miklós , Czeizel Andrew E. , Balogh Lidia , Detre Zoltán
Published: June 2005

We describe two sibs with tetraectrodactyly and oligomeganephronic renal hypoplasia. The parents were unaffected. This syndrome of apparently autosomal recessive origin appears to be the first Mendelian form of the acrorenal developmental field defect identified so far. © 1992 Wiley‐Liss, Inc.
Pericentric inversion of chromosome 16 in a large kindred: Spectrum of morbidity and mortality in offspring
Authors: Bianchi Diana W. , Nicholls Robert D. , Russell Kathryn A. , Miller Wayne A. , Ellin Marvin , Lage Janice M.
Published: June 2005

Constitutional pericentric inversions of chromosome 16 are rare in the general population. We report here a large kindred who carry an inv(16)(p13q22) rearrangement. In general, individuals with the inv(16) are in good health but prone to reproductive loss. Two different types of recombinant offspring were identified in this family and analyzed at the molecular level using probes from the α‐globin and polycystic kidney disease loci. Both were associated with serious major malformations. © 1992 Wiley‐Liss, Inc.
Renal tubular dysgenesis: A not not uncommon autosomal recessive syndrome: A review
Authors: Allanson Judith E. , Hunter Alasdair G. W. , Mettler Gabrielle S. , Jimenez Carmencita
Published: June 2005

Renal tubular dysgenesis is a recently recognized autosomal recessive condition characterized by short and poorly developed proximal convoluted tubules, leading to oligohydramnios, Potter sequence, and neonatal respiratory failure. We report an additional 9 cases from one pediatric center, suggesting that this syndrome is not as rare as was previously thought.

Normal amniotic fluid volumes in affected pregnancies prior to the 22nd week of gestation have been documented, compromising early prenatal diagnosis. Late second trimester sonographic demonstration of oligohydramnios, with structurally normal kidneys, should suggest this diagnosis and the need for detailed post‐mortem pathological examination. © 1992 Wiley‐Liss, Inc.
Neurofibromatosis 1 and osseous fibrous dysplasia in a family
Authors: Schotland Helena M. , Eldridge Roswell , Sommer Steve S. , Malawar Martin
Published: June 2005

We report on the consegregation of neurofibromatosis 1 (NF 1) and osseous fibrous dysplasia in a family. The father and 3 children by 2 women are affected. A fourth child had neither NF 1 nor osseous fibrous dysplasia.

All 4 affected individuals had NF 1, i.e., caféau‐lait spots in 4, neurofibromata in 4, Lisch nodules in 3, macrocrania in 3, scoliosis in 2, and curvature of the long bones in 2. Each demonstrated various fibroosseous lesions of the skeleton including non‐ossifying fibromas in 3 and both non‐ossifying fibromas and fibrous dysplasia in one.

This pattern suggests that the fibrous bony lesions are a component of NF 1 in this family. Alternatively, a mutant gene resulting in the fibrous changes in bone could be linked to the gene for NF 1. Another possibility is the coincidence of the 2 non‐linked traits segregating in the same family. © 1992 Wiley‐Liss, Inc.
Spondyloepiphyseal dysplasia in a cape town family: Linkage with the gene for type II collagen (COL2A1)
Authors: Ramesar Rajkumar , Beighton Peter
Published: June 2005

A moderately severe form of autosomal dominant (AD) spondyloepiphyseal dysplasia (SED) has been documented in 14 individuals in 3 generations of a family in Cape Town, South Africa. Affected persons had a short trunk; radiographic investigations indicated that skeletal involvement was worst in the hips and spine. Linkage studies with restriction fragment length polymorphisms (RFLPs) associated with the COL2A1 gene and the phenotype yielded a maximal LOD score of 4.51 at theta = 0.00. This result suggests that the structural locus for type II collagen is primarily involved in the pathogenesis of this form of SED. © 1992 Wiley‐Liss, Inc.
Combined Goltz and Aicardi syndromes in a terminal Xp deletion: Are they a contiguous gene syndrome?
Authors: Naritomi Kenji , Izumikawa Yoshinori , Nagataki Shigetoshi , Fukushima Yoshimitsu , Wakui Keiko , Niikawa Norio , Hirayama Kiyotake
Published: June 2005

We report on 2 girls with a terminal deletion of the short arm of chromosome X. They had microphthalmia, cloudy corneae, mild linear skin lesions, and agenesis of corpus callosum. A comparison of clinical and cytogenetic findings in similar cases suggested that the critical genes for the Goltz and Aicardi syndromes might be contiguous in the region Xp22.31. © 1992 Wiley‐Liss, Inc.
Prenatal diagnosis with repetitive in situ hybridization probes
Authors: Lebo Roger V. , Flandermeyer Robert R. , Diukman Rony , Lynch Eric D. , Lepercq Jacques A. , Golbus Mitchell S.
Published: June 2005

We have used chromosome‐specific repetitive sequences to detect the most common human aneuploidies prenatally. Together chromosome 21, 13, 18, X, and Y aneuploidy comprises 95% of the chromosome abnormalities that result in a high risk of abnormal phenotypes at birth. The X, Y, and 18 repetitive probes work reliably in multiple tissue types including directly examined and cultured amniocytes, chorionic villus cells, lymphocytes, and cultured fibroblasts. The probe that detects both chromosomes 13 and 21 routinely gives results in each cell type tested except directly studied amniocytes which can be interpreted in seven‐ninths of the cases with protocol 1 and all tested samples with protocol 2. Our protocols diagnosed trisomy 21 in a 23‐week fetus with low maternal serum AFP and a trisomy 18 in a direct chorionic villus sample 2 working days after the samples were obtained. Trisomy 21 also has been ruled out in a CVS karyotype first thought to be 47,XY,+21. These studies reflect the potential value of in situ hybridization to provide a more rapid, less expensive means to screen most at‐risk fetal populations with less effort in first world cytogenetic laboratories, and to provide economical cytogenetic services in less developed countries. © 1992 Wiley‐Liss, Inc.
Analysis of sperm chromosome complements from a man heterozygous for a Robertsonian translocation 45,XY,t(15q;22q)
Authors: Martin Renée H. , Ko Evelyn , Hildebrand Kathy
Published: June 2005

Chromosome complements were studied in 118 sperm from a man heterozygous for a 15;22 Robertsonian trnaslocation using the human sperm/hamster oocyte fusion technique. Alternate segregation occurred in most spreads (89.6%) and the proportion of normal (42.6%) and balanced complements (47%) was approximately equal. The frequency of sperm that were unbalanced with respect to the translocation was 10.4% and all categories of unbalanced sperm were observed (−15, −22, +15, +22). The frequency of chromosome abnormalities unrelated to the translocation was 7.6%. Since the frequencies of both numerical (3.4%) and structural abnormalities (3.4%) were within the normal range of control donors, there was no evidence for an interchromosomal effect. The frequencies of X‐chromosome bearing (48%) and Y‐chromsome bearing (52%) sperm were not significantly different from 50%. Data on this translocation were compared to the 4 other reports of cytogenetic analysis in sperm of Robertsonian translocation carriers. © 1992 Wiley‐Liss, Inc.
A severe case of mandibuloacral dysplasia in a girl
Authors: Schrander‐Stumpel Constance , Spaepen Ann , Fryns Jean‐Pierre , Dumon Jan
Published: June 2005

We report on a 16‐year‐old girl with mandibuloacral dysplasia, a rare progeroid syndrome. She presented at age 2 years with thin skin on the limbs, characteristic face with prominent eyes, a pinched nose, micrognathia, and small mouth. Hair was sparse and brittle. The terminal phalanges were hypoplastic and showed acroosteolysis. On follow‐up, hands and feet showed progressive camptodactyly of fingers and toes with total loss of subcutaneous tissue. The clavicles were hypoplastic. Intelligence was normal. We review the literature on the subject and discuss differential diagnosis. © 1992 Wiley‐Liss, Inc.
Carrier detection and prenatal diagnosis of X‐linked agammaglobulinemia
Authors: Journet O. , Durandy A. , Doussau M. , Le Deist F. , Couvreur J. , Griscelli C. , Fischer A. , de Saint‐Basile G.
Published: June 2005

We investigated the pregnant mother of a boy with X‐linked agammaglobulinemia (XLA) but with no family history of immune disease. The X‐inactivation pattern was found, using a methylation‐sensitive probe, to be skewed in the maternal B cells but random in the polymorphonuclear cells, indicating carrier status and a 50% risk of inheritance for her male fetus. Using probes assigned to regions on either side of the XLA locus and defining RFL polymorphism, we excluded for the first time a diagnosis of XLA on a chorionic villus sample, with a risk of error <0.003. Immunological studies performed at the 19th week of gestation and 3 days after birth confirmed normality. Carrier detection based on the X‐chromosome inactivation pattern, together with prenatal studies using probes close to the disease locus, thus permits prenatal diagnosis in families with isolated cases of XLA. © 1992 Wiley‐Liss, Inc.
A reinvestigation of thirty three fragile(X) families using probe StB12.3
Authors: Macpherson James , Harvey John , Curtis Greta , Webb Tessa , Heitz Dominique , Rousseau Francois , Jacobs Patricia
Published: June 2005

We have reinvestigated 33 fragile X families using probe StB12.3. In 31 families the affected individual showed an insert while in 2 families no insert was detected.

The insert fell into two size categories: small (< 0.5 kb); and large (> 0.6 kb) accompanied by methylation of an EagI site. All individuals of either sex having a small insert were fra(X) negative and intellectually normal, while all males having a large insert were fra(X) positive and intellectually impaired. Females having a large insert were either fra(X) positive or negative and either intellectually normal or impaired.

No new mutation was found. All daughters of males with a small insert had a small insert; females with a large insert produced males and females who had a large insert, while females with a small insert had offspring with either a large or a small insert. However, females with a small insert tended to fall into one of two categories: either they had only children with a small insert or only children with a large insert, there being only one exception to this rule.

We found four unexpected small inserts, two in unrelated spouses and two in female carriers who proved to be compound heterozygotes, indicating that they had inherited an insert from both their parents. These observations suggest that individuals with a small insert must be not uncommon in the general population.
Callosal agenesis, iris coloboma, and megacolon in a Brazilian boy with Rubinstein‐Taybi syndrome
Authors: Guion‐Almeida M. L. , Richieri‐Costa A.
Published: June 2005

We report on a Brazilian boy with Rubinstein‐Taybi syndrome (RTS) with callosal agenesis, iris coloboma, and megacolon. To our knowledge, callosal agenesis, iris coloboma, and megacolon are unusual signs within the clinical spectrum of RTS, and the present association is apparently undescribed. © 1992 Wiley‐Liss, Inc.
Acrocallosal syndrome: Report of a Brazilian girl
Authors: Guion‐Almeida M. L. , Richieri‐Costa A.
Published: June 2005

We report on a Brazilian girl born to nonconsanguineous parents and presenting with frontonasal dysostosis, callosal agenesis, abnormal upper lids, cleft lip/palate, redundant skin in the neck, grooved chin, and bifid thumbs. Major diagnostic criteria present in this patient are related to the acrocallosal syndrome. The clinical and major nosologic aspects of this condition are discussed. © 1992 Wiley‐Liss, Inc.
Unilateral radio‐ulnar synostosis, generalized hypotonia, developmental retardation, and a characteristic facial appearance in sibs: A new syndrome
Authors: Der Kaloustian Vazken M. , McIntosh Nathalie , Silver Kenneth , Blaichman Shirley , Halal Fahed
Published: June 2005

We report on 2 sibs with generalized hypotonia, developmental retardation, unilateral radio‐ulnar synostosis, and a characteristic facial appearance. We propose that they have a new autosomal recessive syndrome. © 1992 Wiley‐Liss, Inc.
X inactivation and dystrophin studies in a t(X;12) female: Evidence for biochemical normalization in Duchenne muscular dystrophy carriers
Authors: Wenger Sharon L. , Steele Mark W. , Hoffman Eric P. , Barmada Mamdouha A. , Wessel Henry B.
Published: June 2005

A 4‐year‐old girl was identified with high creatine kinase (CK) values, and mild muscle weakness in a limb‐girdle distribution. Results of dystrophin analysis of the muscle biopsy were consistent with a manifesting heterozygote for Duchenne muscular dystrophy. In peripheral lymphocytes she had a t(X;12) (p21.2;q24.33). Late DNA replication studies demonstrated inactivation of the normal X chromosome in 99.4% of cells. Dystrophin immunofluorescence showed 64% dystrophin‐negative muscle fibers. Dystrophin content of muscle by immunoblot was approximately 5% of normal. The discordance between the percent of normal X inactivation and percent of dystrophin‐negative cells may be explained by compensatory protection of dystrophin by rare nuclei with the normal X active in multinucleated muscle fibers with shared cytoplasm. © 1992 Wiley‐Liss, Inc.
Microcephaly, lymphedema, and chorioretinal dysplasia: A distinct syndrome?
Authors: Feingold Murray , Bartoshesky Louis
Published: June 2005

We report on 2 unrelated patients with microcephaly, lymphedema, and chrorioretinal changes. They are compared with previously reported patients with microcephaly and lymphedema and microcephaly with chorioretinal changes. The question is raised whether all of these patients represent one entity or are separate syndromes. Until more data are available we propose that our patients represent a single entity. © 1992 Wiley‐Liss, Inc.
VACTERL with hydrocephalus: One end of the Fanconi anemia spectrum of anomalies?
Authors: Porteous M. E. M. , Cross I. , Burn J.
Published: June 2005

Two cases of Fanconi anemia presenting as hydrocephalus are discussed. Both infants had initially been considered to have features of VACTERL. Chromosomal breakage studies should be performed in all cases of VACTERL with hydrocephalus so that Fanconi anemia may be excluded. © 1992 Wiley‐Liss, Inc.
Hawkinsinuria in two families
Authors: Borden Margaret , Holm Jan , Leslie Jack , Sweetman Lawrence , Nyhan William L. , Fleisher Lynn , Nadler Henry , Lewis David , Scott C. Ronald
Published: June 2005

Hawkinsinuria, a disorder of tyrosine metabolism has been documented in two families in the United States, in one of which there was clear evidence of autosomal dominant inheritance. Metabolic acidosis and failure to thrive appear to be confined to infancy. Tyrosyl metabolites and 5‐oxoproline are also found only in infancy, while 4‐hydroxycyclohexylacetic acid was present only with time. The disease may be detected by organic acid analysis or by staining an electropherogram for sulfur containing compounds. © 1992 Wiley‐Liss, Inc.
Anencephaly and limb deficiencies
Authors: Rodríguez José Ignacio , Rodríguez‐Peralto José L. , Muro Marta , Urioste Miguel , Palacios José
Published: June 2005

Limb deficiencies (LDs) are rarely reported in anencephalic infants. A review of 662 patients in the literature on non‐neural defects in an‐encephaly only showed five patients with LDs. We report on eight patients with various LDs from the records of 141 necropsies of the anencephalic infants found among 495,830 births. Compared with another group of anencephalic infants reported in the literature, the patients in this group of anencephalic infants with LDs were predominantly male, their mean gestational age was younger by approximately 5 weeks, their mean birth‐weight was approximately 1,400 g less, and they presented with a higher incidence of polyhydramnios during gestational development. The association of this pair of anomalies, which was 100 times more frequent than expected, seems not due to chance. Since all eight patients had other multiple congenital anomalies (MCA), in addition to anencephaly and LDs, the postmortem study should be mandatory in anencephalic infants with LDs. The most common associated anomalies were cardiovascular and renal defects. Oral clefts, diaphragmatic hernia, esophageal atresia, and imperforate anus were also observed in these infants. The recognition of LDs in anen‐cephalic infants indicates severe and extensive disturbance of the early embryogenesis (blastogenesis), which affects the midline of the embryo. © 1992 Wiley‐Liss, Inc.
Confirmation of assigment of a locus for rubinstein‐taybi syndrome gene to 16p13.3
Authors: Lacombe Didier , Saura Robert , Taine Laurence , Battin Jacques
Published: June 2005

A two month‐old girl was diagnosed as a case of Rubinstein‐Taybi syndrome (RTS) on typical facial dysmorphism, broad and duplicated distal phalanges of thumbs and halluces, growth retardation and psychomotor development delay. Chromosome analysis demonstrated a de novo pericentric inversion of one chromosome 16: 46,XX,inv(16)(p13.3;q13). This association confirms assignment of a locus for RTS gene to 16p13.3, as two others translocations involving the same breakpoint have already been reported. © 1992 Wiley‐Liss, Inc.
Human smooth muscle myosin heavy chain gene mapped to chromosomal region 16q12
Authors: Matsuoka Rumiko , Yoshida Michihiro C. , Furutani Yoshiyuki , Imamura Shin‐Ichiro , Kanda Naotoshi , Yanagisawa Masashi , Masaki Tomoh , Takao Atsuyoshi
Published: June 2005

The partial nucleotide sequence encoding the rod portion of the entire amino acid sequence of human smooth muscle myosin heavy chain (MHC) which corresponds to MYH11, according to Human Gene Mapping nomenclature, has been determined by cloning a complementary DNA (cDNA) and sequencing the cDNA (UMYHSM). Northen blot analysis with the UMYHSM fragment (4.3 Kb) showed that the smooth muscle MHC of the human umbilical artery is expressed in the human umbilical artery, bladder, esophagus and trachea. Southern blot analysis of human genomic DNA from human‐mouse or human‐Chinese hamster somatic cell hybrids demonstrated that the human smooth muscle MHC was mapped to human chromosome 16. Regional mapping of UMYHSM was performed using human cell lines with partial deletion and trisomy of chromosome 16. As a result, the human smooth muscle MHC gene segregated with 16p11‐q12. In situ hybridization of biotin‐labeled human smooth muscle MHC probe (UMYHSM fragment) to normal human metaphase chromosome independently showed that the human smooth muscle MHC gene (MYH11) is assigned to chromosome region 16q12. Analysis of early metaphase chromosomes showed that hybridization signals were in 16q12.1. In the human, although skeletal, cardiac, smooth muscle, and nonmuscle MHC genes are mapped to chromosomes 17, 14, 16 and 22, respectively, structural similarities of these MHC genes strongly suggest the common origin of these genes. © 1993 Wiley‐Liss, Inc.
Method for sequential staining of GTL‐banded metaphases with fluorescent‐labeled chromosome‐specific paint probes
Authors: Jalal Syed M. , Law Mark E. , Christensen Eric R. , Spurbeck Jack L. , Dewald Gordon W.
Published: June 2005

We describe a method for use of fluorescent‐labeled whole chromosome‐specific paint probes on GTL‐banded metaphases to utilize the combined potential of these techniques for defining chromosome abnormalities. The efficacy of this method was tested on 6 cases involving different chromosome abnormalities and various tissues, including blood, amniotic fluid, skin fibroblasts, and bone marrow. © 1993 Wiley‐Liss, Inc.
Age of onset in familial early onset Alzheimer's disease correlates with genetic aetiology
Authors: Mullan Michael , Houlden Henry , Crawford Fiona , Kennedy Angus , Rogues Penelope , Rossor Martin
Published: June 2005

Age of onset is the most robust clinical feature demarcating aetiologic subtypes of familial Alzheimer's disease. It has previously been noted that early onset disease (arbitarily below the age of 65 years) conforms to an autosomal dominant pattern of transmission. Late onset disease is generally thought to have a more complex aetiology. We present data here suggesting that early onset disease can be subdivided by genetic aetiology with which age of onset correlates. In general, those pedigrees showing linkage to the chromosome 14 locus have a mean age of onset in the forties whereas those pedigrees with an APP mutation have an age of onset in the fifties. © 1993 Wiley‐Liss, Inc.
Lack of variation in the nucleotide sequence corresponding to the transmembrane domain of the β‐amyloid precursor protein in Alzheimer's disease
Authors: Zubenko George S. , Stiffler Scott , Farr Joan , Kopp Ursula , Hughes Hugh , Kaplan Barry B. , Moossy John
Published: June 2005

The nucleotide sequence corresponding to the APP transmembrane domain and flanking regions of charged amino acids was determined for 91 patients with histologically confirmed Alzheimer's disease, 9 patients with dementias of other etiologies, and 14 controls who had no identifiable brain disease. Twentyeight of the AD patients had a first‐degree relative with dementia. No mutations were detected among the 100 demented patients. However, one of the 14 controls exhibited a change in the 3′ base of codon 716 which would not be expected to result in an amino acid substitution at this position. © 1993 Wiley‐Liss, Inc.