bluuebunny/crossref_metadata_2025 huggingface dataset:
A visual interface to computer programs for linkage analysis
Authors: Chapman Cyril J.
Published: June 2005

This paper describes a visual approach to the input of information about human families into computer data bases, making use of the GEM graphic interface on the Atari ST. Similar approaches could be used on the Apple Macintosh or on the IBM PC AT (to which it has been transferred). For occasional users of pedigree analysis programs, this approach has considerable advantages in ease of use and accessibility. An example of such use might be the analysis of risk in families with Huntington disease using linked RFLPs. However, graphic interfaces do make much greater demands on the programmers of these systems.
Interrupted aortic arch type B1 in a brother and sister: Suggestion of a recessive gene
Authors: Pankau Rainer , Funda Johannes , Wessel Armin
Published: June 2005

We report on the occurrence of an identical form of interrupted aortic arch and ventricular septal defect in a brother and sister whose parents are not consanguineous. The first child died on the 7th day of life without surgery 3 years ago; the second underwent surgical correction on the 5th day of life and is doing well.
Analysis Of cultured chorionic villi in a case of osteogenesis imperfecta type II: Implications for prenatal diagnosis
Authors: Grange Dorothy K. , Lewis Mary Beth , Marini Joan C.
Published: June 2005

We examined collagens produced by cultured cells from skin, chorionic villi, and placental membranes of a 32 week fetus with osteogenesis imperfecta (OI) type II. We observed that skin fibroblasts synthesized two populations of pro∝︁I(I) chains of type I procollagen; one population was normal, while the other population had excessive post‐translational modification. The thermal stability of helices containing the overmodified chains was reduced 1‐2°C. Most significantly, the cells cultured from chorionic villi produced type I collagen chains with the same electrophoretic abnormalities as the skin collagen. This suggests that chorionic villus sampling (CVS) is a means of prenatal diagnosis for families with a previous type II or type IV OI infant.
Hypotrichosis with spondyloepimetaphyseal dysplasia in three generations: A new autosomal dominant syndrome
Authors: Whyte Michael P. , Petersen Deborah J. , McAlister William H.
Published: June 2005

We describe a family with a new disorder characterized by congenital hypotrichosis and spondyloepimetaphyseal dysplasia that results in mild rhizomelic short stature. Five individuals in 3 generations are affected with autosomal dominant inheritance.
Percent transferrin saturation in segregating hemochromatosis
Authors: Borecki I. B. , Rao D. C. , Yaouanq J. , Lalouel J. M.
Published: June 2005

The segregation of genetic hemochromatosis was analyzed by using percent transferrin saturation (TS) as a phenotypic marker of the disease. Homozygotes for the disease were readily discernable with the added information provided by the quantitative indicator. However, there was no evidence of partial expression of TS abnormalities in heterozygotes, contrary to previous studies.
Chediak‐Higashi syndrome in the cat: Prenatal diagnosis by evaluation of amniotic fluid cells
Authors: Kahraman M. Müfit , Prieur David J.
Published: June 2005

Chediak‐Higashi syndrome (CHS) is an autosomal recessive disease in humans, cats, and 8 other species. The homology of CHS in humans and cats has been demonstrated. Since human CHS is a progressive, serious, and eventually fatal disease, a method for prenatal diagnosis would be desirable. This study was designed to determine whether CHS could be diagnosed prenatally by examination of amniotic fluid cells. The amniotic fluid samples were obtained from CHS and control cat fetuses on the 45th day of gestation and cultures of cells were established. Because the underlying enzyme deficiency in CHS has not been identified, it was necessary to use a secondary manifestation of the syndrome in these studies. The secondary manifestation used was the characteristic enlargement of lysosomes associated with the disease. The lysosomes of these cells were stained by acid phosphatase histochemistry and the diameter of the largest lysosome in each cell was measured by light microscopy with a calibrated ocular micrometer. The diameters of the largest lysosomes in cells of normal fetuses ranged from 0.5 to 7.0 μm (means ranged from 0.9 to 1.8 μm), whereas the diameter of the largest lysosomes in the cells of CHS fetuses ranged from 0.5 to 30 μm (means ranged from 6.4 to 12.8 μm). The approximate t‐test for independent samples with unequal variances disclosed that the largest acid phosphatase‐positive lysosomes in amniotic fluid cells of CHS cat fetuses were significantly larger than the lysosomes in the cells of normal cat fetuses (P < 0.0001). This information should, by extrapolation, provide the basis for the prenatal diagnosis of human CHS by amniocentesis.
Proximal interstitial deletion of 7q: A case report and review of the literature
Authors: Zackowski Joleen L. , Raffel Leslie J. , Blank Carol A. , Schwartz Stuart
Published: June 2005

A male infant with multiple congenital anomalies was found to have a deletion of 7q [46, XY, del(7)(pter→q11.2::q22→qter)]. The father had a balanced rearrangement involving chromosomes 7 and 9, interpreted as 46,XY,dir ins(9;7) (9pter→ 9p12::7q22→ 7q11.2::9p12→ 9qter;7pter→ 7q11.2::7q22→ 7qter). C‐banding showed that the rearrangement occurred as a new event in the paternal grandfather's germ‐line.

Including the present patient, 16 cases of proximal 7q deletion (q11→q21/q22) have been described to date. This is a sufficient number of cases to permit comparison of manifestations to attempt delineation of karyotype‐phenotype relationships in different proximal interstitial deletions of 7q.
Genetics of conotruncal malformations: Review of the literature and report of a consanguineous kindred with various conotruncal malformations
Authors: Rein Azaria J. J. T. , Dollberg Shaul , Gale Rena
Published: June 2005

Genetic predisposition in congenital heart disease is considered to be a component of multifactorial inheritance. Recently, monogenic inheritance in conotruncal malformations has been suggested. We describe a consanguineous kindred with various conotruncal malformations, the presence of which lends support to the idea that this spectrum of malformation is monogenically inherited.

Theoretical background and experimental and clinical data are reviewed and discussed.
Syndrome of congenital cutis laxa with ligamentous laxity and delayed development: Report of a brother and sister from Turkey
Authors: Oğur Gönül , Yüksel‐Apak Memnune , Demiryont Misten
Published: June 2005

Congenital cutis laxa with ligamentous laxity and delayed development has recently been defined as a distinct entity of autosomal recessive inheritance. Here we report on 2 new cases of this syndrome. With severe manifestations in the male, X‐linked dominant inheritance is discussed. Results of ultrastructural studies of skin and biochemical studies are reported.
Mesomelic dysplasia with absence of fibulae and hexadactyly: Nievergelt syndrome or new syndrome?
Authors: Petrella Rena , Ludman Mark D. , Rabinowitz Jack G. , Gilbert Fred , Hirschhorn Kurt
Published: June 2005

Mesomelic dysplasia is a form of short‐limb dwarfism characterized by disproportionate shortness of the middle segment of all limbs. Included in this category of skeletal disorders is the Nievergelt syndrome, which typically manifests a rhomboidal shape of the tibiae and fibulae, an unusual foot deformity, radio‐ulnar synostosis, and dysplasia of the elbow and knee joints. We describe a patient with mesomelic dysplasia with findings suggestive of the Nievergelt syndrome and with absence of fibulae and hexadactyly.
EEC syndrome: Report on 20 new patients, clinical and genetic considerations
Authors: Rodini Elaine S. O. , Richieri‐Costa A.
Published: June 2005

We report on 20 Brazilian patients (11 sporadic and 9 familial cases) with the ectrodactyly, ectodermal dysplasia, clefting syndrome (EEC syndrome). Genetic aspects, clinical manifestations, and differential diagnosis of the syndromes involving ectodermal dysplasia/limb anomalies and cleft lip/palate are discussed.
Determining the origins and the structural aberrations of small marker chromosomes in two cases of 45,X/46,X, +mar by use of chromosome‐specific DNA probes
Authors: Lin C. C. , Meyne Juliane , Sasi Ramakrishnan , Bowen Peter , Unger T. , Tainaka Tomomi , Hadro Teresa A. , Hoo Joe J.
Published: June 2005

A 17‐year‐old girl (S.M.) and a 13‐year‐old girl (C.L.) both with Ullrich‐Turner syndrome (UTS) were found to have 45,X/46,X, +mar mosaicism. The marker chromosomes in both patients were very small in size. In S.M. the marker chromosome was present in 80% of phytohemaglutinin‐stimulated lymphocytes, 28% of skin fibroblasts, and 11–20% of gonadal fibroblasts. In C.L., the small marker chromosome was found in 50% of stimulated lymphocytes. S.M. is of normal height, but C.L. is short. Molecular hybridization with a number of Y‐specific DNA probes demonstrated their presence in S.M. but absence in C.L. In situ hybridization with Y‐specific and X‐centromere‐specific DNA probes confirmed the Y origin of the marker chromosome in S.M. and the X origin of the minute chromosome in C.L. Biotinylated centromere and telomere probes were also used for in situ hybridization to show the presence of centromeric and telomeric sequences in the Y‐marker chromosome, suggesting that the deletion of this marker chromosome is interstitial.
Ring chromosome 4 in a child with duodenal atresia
Authors: Halal Fahed , Vekemans Michel
Published: June 2005

We report on a 19‐month‐old girl with ring chromosome 4 and a multiple congenital anomaly syndrome. The clinical and cytogenetic findings are compared with those of previous cases in whom the breakpoints in ring chromosome 4 are known.
Transient hypoglycemia with hyperinsulinemia in a newborn infant with Rubinstein–Taybi syndrome
Authors: Wyatt David
Published: June 2005

A newborn boy with Rubinstein–Taybi syndrome who had profound neonatal hypoglycemia is presented. The infant was a discordant fraternal twin with intrauterine growth retardation. The hypoglycemia was due to transient hyperinsulinemia, a condition often seen in small‐for‐gestational‐age infants. Neonatal hypoglycemia may be common in infants with Rubinstein–Taybi syndrome, especially if they also have intrauterine growth retardation.
Neurologic manifestations in 18q– syndrome
Authors: Miller Geoffrey , Mowrey Philip N. , Hopper Kenneth D. , Frankel Carl A. , Ladda Roger L.
Published: June 2005

We report a mother and son with a deletion at 18q22.3. Both have the typical manifestations of the 18q– syndrome. In addition, both have an action tremor which became apparent in childhood. The mother subsequently developed chorea and dysmetria in late adolescence. Magnetic resonance imaging of their brains showed poor myelination of the central white matter tracts with relatively normal myelination of the corpus callosum. We propose that these neurologic findings are most likely due to a failure of expression of the myelin basic protein gene.
Marfan syndrome associated with bicuspid aortic valve, premature aging, and primary hypogonadism
Authors: Gershoni‐Baruch R. , Moor E. V. , Enat R.
Published: June 2005

We report on a patient with classical manifestations of Marfan syndrome (MS) and unusual findings such as bicuspid aortic valve (BAV), premature aging, and primary hypogonadism.
Patterns of mood states in pregnant women undergoing chorionic villus sampling or amniocentesis
Authors: Tunis Sandra L. , Golbus Mitchell S. , Copeland Karen L. , Fine Beth A. , Rosinsky Barbara J. , Seely Linda
Published: June 2005

The purpose of this study was to compare paterns of self‐reported mood states of women having chorionic villus sampling (CVS) (n = 151) to those of women electing amniocentesis (n = 30) with the indication of advanced maternal age. Mood states were defined as scores on the 6 subscales of the Profile of Mood States (POMS). Women at 4 U.S. prenatal diagnostic facilities completed the POMS at 4 assessment periods. These were (a) at their initial genetic counseling session, (b) 2 weeks post CVS results (or an equivalent time), (c) 2 weeks post amniocentesis results (or an equivalent time), and (d) at 30 weeks gestation. Repeated measures analysis of variance revealed that anxiety, fatigue, and confusion decreased, and vigor increased in both groups as the pregnancy progressed. Depression decreased in both groups and then increased at assessment 4 in women in the amniocentesis group but not in those electing CVS. Results should be interpreted in conjunction with obstetrically and genetically‐oriented findings regarding safety and accuracy to help women decide between the 2 procedures.
New type of X‐linked progressive muscular dystrophy involving shoulder girdle and back
Authors: Ji Xue‐Wen , Tan Jun , Chen Xiao‐Yi , Yi Shao‐Xuan , Liang Hong
Published: June 2005

A new type of X‐linked muscular dystrophy is described in a family in which 7 men had boyhood onset of progressive dystrophy involving muscles of the shoulder and back but not the calves or face. The scapula‐back muscles are affected, but the calf muscles are normal. All patients are still able to walk. The oldest patient is now 37 years old. The muscular dystrophy has been specified by electromyography, pathologic tissue microscopic examination, electron microscopic study, and elevated CK. This type of muscular dystrophy has not been reported previously.
Arthrogryposis, cholestatic pigmentary liver disease and renal dysfunction: Report of a second family
Authors: Di Rocco M. , Reboa E. , Barabino A. , Larnaout A. , Canepa M. , Savioli C. , Cremonte M. , Borrone C.
Published: June 2005

We report on a boy, born to consanguineous parents, who had arthrogryposis, cholestatic liver disease, and renal dysfunction. The child died at age 2 months, and autopsy showed pigmentary storage disease in liver cells, nephrocalcinosis, and rarefaction of motor neuron cells in the anterior horns of spinal cord. This association, reported in 1979 by Nezelof et al., is a distinctive syndrome. The possibility of an autosomal recessive or an X‐linked inheritance is discussed.
Holoprosencephaly: Examples of clinical variability and etiologic heterogeneity
Authors: Corsello Giovanni , Buttitta Piera , Cammarata Marina , Lo Presti Alfio , Maresi Emiliano , Zumpani Luigi , Giuffrè Liborio
Published: June 2005

Clinical variability and causal heterogeneity of holoprosencephaly is discussed in relation to several newborn infants with cyclopia (cases 4,5,6), cebocephaly (cases 2,3), and premaxillary agenesis (case 1). In subjects with holoprosencephaly, the presence of multiple malformations is an indicator of concomitant chromosome aberrations, as in present case 1 (Down syndrome) and case 3 (trisomy 13). Cases 5 and 6 are two monozygotic twins with the same type of cyclopia and alobar holoprosencephaly recognized by prenatal ultrasonographic, cytogenetic, and pathological studies is pointed out in view of etiologic evaluation, genetic counseling, and prevention of holoprosencephaly.
Clinical diagnosis of partial duplication 7q
Authors: Bartsch Oliver , Kalbe Udo , Ngo Thi Kim Nhan , Lettau Reinhard , Schwinger Eberhard
Published: June 2005

We report on two sibs with partial dup (7q), a retarded 9‐month‐old boy and an aborted fetus of 17 weeks' gestational age. Besides minor anomalies, the boy had frontal bossing, macrocephaly with hydrocephaly, a high forehead, and a large fontanelle. GTG banded chromosomes showed a 14p+ abnormality. Because his mother carries a balanced, de novo translocation with a breakpoint in band 7q33, the boy has a duplication of the distal portion of band 7q33 and the segment 7q34 qter. Our findings suggest that the phenotype in terminal duplications of 7q may, in some patients, be recognized clinically.
Acrofacial dysostosis with ambiguous genitalia
Authors: Wulfsberg Eric A. , Curtis Jerri , Wiswell Thomas E. , Puntel Robert A. , Levin Sondra W.
Published: June 2005

We report on a 46,XY infant with mandibulofacial dysostosis, preaxial and postaxial limb anomalies, urethral stenosis with left hydronephrosis, and ambiguous genitalia with phallic/scrotal transposition. This infant with atypical pre/postaxial acrofacial dysostosis (AFD) is the first to be reported with ambiguous genitalia. The acrofacial dysostoses are a heterogenous group of disorders characterized by varying degrees of mandibulofacial dysostosis with acral limb defects and may represent a polytopic field defect. These disorders have generally been separated on the basis of their limb anomalies into preaxial, postaxial, lethal, and atypical types. Most cases are sporadic, but various causes have been postulated including autosomal dominant and recessive inheritance, a chromosome 2q duplication, and a possible case of diabetic embryopathy. We review the nonfacial/limb anomalies in other cases of AFD and compare them to those of our case, thereby expanding the spectrum of anomalies in these disorders.
Incidence of tuberous sclerosis in patients with cardiac rhabdomyoma
Authors: Harding Cary O. , Pagon Roberta A.
Published: June 2005

Cardiac rhabdomyoma, a rare benign tumor often detected in infancy, is frequently associated with tuberous sclerosis. This association is commonly stated to occur in 50% of all cases of cardiac rhabdomyoma. Recently at our institution, the prenatal detection of a cardiac rhabdomyoma in a fetus at no known risk for tuberous sclerosis emphasized the need to determine the frequency of association in order to provide accurate diagnosis and counseling in such situations. After a review of reported cases and review of patients from our institution diagnosed to have cardiac rhabdomyoma, we estimate that 51–86% of cardiac rhabdomyomas are associated with tuberous sclerosis. We present the results of our literature and case review.
Baller‐Gerold syndrome: An 11th case of craniosynostosis and radial aplasia
Authors: Boudreaux Jeanne M. , Colon Marc A. , Lorusso Giovanni D. , Parro Elizabeth A. , Pelias Mary Z.
Published: June 2005

We report on a patient with craniosynostosis, left radius aplasia, right radius hypoplasia, and other congenital anomalies. This is the 11th reported case of the Baller‐Gerold syndrome. Autosomal recessive inheritance of this syndrome is suggested by evidence of probable parental consanguinity.
Opitz C syndrome and pseudohypoaldosteronism
Authors: De Koster Jan , Legius Eric , De Zegher Francis , Devlieger Hugo , Fryns Jean‐Pierre , Eggermont Ephrem
Published: June 2005

The C syndrome of multiple congenital anomalies is described in a male infant with pseudohypoaldosteronism. The association of these 2 rare autosomal recessive conditions is discussed.
Persistent hyperinsulinemic hypoglycemia of infancy (“nesidioblastosis”): Autosomal recessive inheritance in 7 pedigrees
Authors: Glaser Benjamin , Phillip Moshe , Carmi Rivka , Lieberman Ester , Landau Heddy
Published: June 2005

Persistent Hyperinsulinemic Hypoglycemia of Infancy (PHHI) is a rare disease characterized clinically by persistent hypoglycemia with inappropriately elevated circulating insulin concentrations. Here we report on 7 pedigrees including 21 cases. The pedigrees are derived from 3 distinct ethnic groups, and include a very large Bedouin family, and Arab family, and 5 smaller pedigrees of Jewish families all of Eastern European origin. Data obtained from these families and from other families reported in the literature strongly suggest that PHHI is inherited as an autosomal recessive disorder.
Monozygotic twins discordant for the Russell‐Silver syndrome
Authors: Samn Michael , Lewis Kathleen , Blumberg Bruce
Published: June 2005

Russell‐Silver syndrome is a disorder of unknown cause. A number of familial cases have suggested autosomal dominant inheritance. We report on monozygotic twins discordant for the Russell‐Silver syndrome. Our findings suggest that the cause of Russell‐Silver syndrome is not explained entirely by genetic factors. The possible role of the intrauterine environment as an etiologic component of Russell‐Silver syndrome is discussed.
Cohen syndrome and de novo reciprocal translocation t(5;7) (q33.1;p15.1)
Authors: Fryns Jean‐Pierre , Kleczkowska Alice , Smeets Eric , Thiry Paul , Geutjens Jaak , Van den Berghe Herman
Published: June 2005

Here we report on a de novo apparently balanced reciprocal 5q;7p translocation in a 15‐year‐old girl with apparent Cohen syndrome characterized by hypotonia, obesity, multiple congenital anomalies, and mental retardation. This case may indicate that the gene for Cohen syndrome is at 5q33.1 or 7p15.1.
Sexual discordance in monozygotic twins
Authors: Perlman Elizabeth J. , Stetten Gail , Tuck‐Müller Cathy M. , Farber Rosann A. , Neuman Wilma L. , Blakemore Karin J. , Hutchins Grover M.
Published: June 2005

We report on monozygotic (MZ) twins who were discordant for phenotypic sex and UIIrich‐Turner syndrome (UTS). The nonviable female was hydropic with cystic hygromas, ventricular septal defect, bicuspid aortic valve, polysplenia, intestinal malrotation, and small ovaries. The male was phenotypically normal. The monochorionic, diamniotic placenta had hydropic changes limited to the UTS infant's side. Skin samples from the infants and blood from their parents were obtained for cytogenetic and molecular analysis. Karyotypes of the twins were 45,X and 46,XY. Quinacrine polymorphisms on 7 chromosomes and RFLP analysis at 8 loci showed complete identity. MZ twins discordant for phenotypic sex have been described previously. Most of these show evidence of mosaicism in a 45,X patient with a normal 46,XY cell line, and a normal 46,XY male. While the issue of mosaicism in our case cannot be fully resolved, no mosaicism was found in 50 cells analyzed cytogenetically from each culture or by PCR analysis of a Y‐specific sequence. The twins probably originated from either postzygotic nondisjunction or anaphase lag, followed or accompanied by twinning. The discordant placental morphology suggests an embryonic origin of at least part of the placental mesenchymal core.
ADAM sequence and innocent amniotic band: Manifestations of early amnion rupture
Authors: Yang S. Samuel
Published: June 2005

Thirteen placentas with early amnion rupture (EAR) are described. These placentas were characterized by the absence of amniotic epithelium on the fetal surface, presence of a slightly fibrotic small amniotic band (remnant) attaching to the umbilical cord at the placental end, and the presence of degenerated vernix squamous cells in the fibrous stroma of chorion and amnion. Eight fetuses had ADAM sequence. Six of these fetuses were miscarried between 16 and 28 weeks of gestation. Two affected infants were born alive at gestational ages of 29 and 39 weeks. Five infants were spared by ADAM sequence; two had the umbilical cord strangulated by an amniotic band and were delivered at 27 and 37 weeks. In the 3 infants unassociated with ADAM sequence or strangulation of the umbilical cord, their placentas were interpreted as having innocent amniotic band (IAB) and they were delivered between 32 and 40 weeks. The findings in this study support Torpin's hypothesis that ADAM sequence is a complication of EAR. This ADAM sequence due to simple EAR must be separated from the limb body wall malformation complex because visceral anomalies are uncommon in the former condition but are frequently seen in the latter. In this study the placental pathology of EAR was helpful in confirming the ADAM sequence in the fetus.
Roberts syndrome or “X‐linked amelia”?
Authors: Gershoni‐Baruch Ruth , Drugan Arie , Bronshtein Moshe , Zimmer Etan Z.
Published: June 2005

We report on a syndrome of tetra‐amelia, facial clefts, absence of ears, nose, and atresia ani, affecting 7 male infants or fetuses in one Arab Moslem kindred. The combination of anomalies described in each affected member is consistent with Roberts syndrome and the prevalence of intermarriage in this kindred could suggest an autosomal recessive mode of inheritance. Alternatively, the existence of a new syndrome, namely, “X‐linked amelia” is proposed.
Prenatal diagnosis of Fraser syndrome at 18.5 weeks gestation, with autopsy findings at 19 weeks
Authors: Schauer G. M. , Dunn L. K. , Godmilow L. , Eagle R. C. , Knisely A. S.
Published: June 2005

Sonography permitted the diagnosis of Fraser syndrome (cryptophthalmos‐syndactyly syndrome) at 18.5 weeks of gestation in a fetus whose parents had had a previous affected child. The karyotype of that child was 46,XX,inv(9)(p11q21); the karyotype of the phenotypically normal father and of the fetus was 46,XY,inv(9)(p11q21). Findings on sonography included oligohydramnios with nonvisualization of kidneys, hypertelorism and microphthalmia, and markedly enlarged lungs. On autopsy at 19 weeks, findings included renal agenesis, cryptophthalmos with multiple abnormalities of the eyes and ocular adnexa, laryngeal atresia, pulmonary hyperplasia with accelerated maturation, absence of the Eustachian tube with connective tissue occuying the tympanic cavity and bone occluding the external acoustic meatus, and soft‐tissue webbing between the digits. This is the second reported instance of prenatal diagnosis of Fraser syndrome in the second trimester. The histopathologic findings in Fraser syndrome at this gestational age, in particular the eye and ear, have not been described previously.
A familial MCA/MR syndrome due to translocation t(10;16)(q26;p13.1): Report of six cases
Authors: Bofinger Mary K. , Opitz John M. , Soukup Shirley W. , Ekblom Linda S. , Phillips S. , Daniel Arthur , Greene Edward W.
Published: June 2005

A minute familial translocation t(10;16) (q26;p13.1) was detected in a family with 6 affected children in 2 generations and 9 carriers in 3 generations. This apparently unique translocation is associated with a deleterious syndrome which includes fetal hydrops, ascites, complex congenital heart defect, psychomotor retardation, failure to thrive, hypotonia, narrow palpebral fissures, abnormally modeled, apparently low‐set ears, cleft palate, thumb abnormalities, hypogenitalism, inguinal hernia, and sparse hair. All children of known or presumed carriers have been either balanced or unbalanced carriers of this translocation.
Routine use of methods for improved G‐band resolution in a population of patients with malformations and developmental delay
Authors: Mascarello J. T. , Hubbard V.
Published: June 2005

We report on an 11‐year experience in which cell culture synchronization and other methods for improving cytogenetic detail were used to study 2,245 patients presenting with malformations and (usually) developmental delay. Not including patients presenting with one of the so‐called “contiguous gene syndromes,” 30 patients (1.1% of the study population) were found to have karyotypes characterized by structural alterations that were either subtle enough to be judged undetectable in standard metaphase preparations or subtle enough to have escaped detection in previous banded studies. Analysis of the detail available for 6 chromosome pairs suggests that the average banding detail available for these analyses fell short of that considered to be “high‐resolution” but was, nevertheless, more than would have been expected from standard metaphase preparations.
Autosomal recessive inheritance of vasopressin‐resistant diabetes insipidus
Authors: Langley J. M. , Balfe J. W. , Selander T. , Ray P. N. , Clarke J. T. R.
Published: June 2005

We report on 2 intellectually normal sisters with vasopressin‐resistant (nephrogenic) diabetes insipidus (NDI). The sex of the patients, the history of parental consanguinity, and the fact that both parents formed normally concentrated urine suggested that the NDI in the 2 sisters was the result of inheritance of an autosomal recessive mutation affecting renal tubular water reabsorption. The results of DNA analysis of the DXS52 locus with the use of St14 as probe, shown by Knoers et al. [1988] to be tightly linked to the NDI locus on the X‐chromosome, showed that each girl inherited different Xq28 regions of the maternal X chromosomes, ruling out a diagnosis of classical X‐linked NDI.
Fibrochondrogenesis in male twins at 24 weeks gestation
Authors: Bankier A. , Fortune D. , Duke J. , Sillence D. O.
Published: June 2005

Fibrochondrogenesis is a rare lethal chondrodysplasia. Only 5 cases have been reported. We report on a pair of affected twins diagnosed at 24 weeks of gestation. Occurrence in sibs and consanguinity in the parents in a previous report support autosomal recessive transmission.
A new mutation in the proteolipid protein (PLP) gene in a German family with pelizaeus‐merzbacher disease
Authors: Pratt Victoria M. , Trofatter James A. , Schinzel Albert , Dlouhy S. R. , Conneally P. M. , Hodes M. E.
Published: June 2005

A C‐to‐T transition in exon 4 of the PLP gene was found in 2 affected males and two obligate carriers in a German family with Pelizaeus–Merzbacher disease. The mutation, which causes loss of an HphI site and changes amino acid 155 from threonine to isoleucine, was absent from 108 normal chromosomes. There are 5 concordances and 1 discrepancy between these results and those obtained by magnetic resonance imaging in this family.
Linkage analysis in families with autosomal recessive limb‐girdle muscular dystrophy (LGMD) and 6q probes flanking the dystrophin‐related sequence
Authors: Passos‐Bueno Maria Rita , Terwilliger Joseph , Ott Jürg , Vainzof Mariz , Love Donald R. , Davies Kay E. , Zatz Mayana
Published: June 2005

The clinical similarity with the X‐linked muscular dystrophies and the uniqueness of the homology between the DMD‐like and the 1.8 kb sequeces at the carboxyterminal domain of the dystrophin gene led to the suggestion that this 6q sequence might be a strong candidate for one of the autosomal recessive muscular dystrophies. Thus, we tested, through linkage analysis, if 6q probes flanking the dystrophin‐homologous sequence are linked to the gene responsible for limb‐girdle dystrophy (LGMD).

A total of 226 individuals (57 patients and 169 unaffected relatives) from 19 large unrelated Brazilian families was studied.

Results of two‐point aalysis excluded linkage with MYB (6q22–23) and ESR (6q24–q27) at θ=0.10 and with TCP1 (6q25–q27) at θ=0.05, indicating that the LGMD gene is not in the 6q23–q27 region. Therefore, the dystrophin‐homologue sequence is not the gene responsible for LGMD.
XLMR genes: Update 1990
Authors: Neri Giovanni , Gurrieri Fiorella , Gal Andreas , Lubs Herbert A.
Published: June 2005

We have identified 39 X‐linked conditions in which mental retardation seems to be the primary characteristic, although pathogenesis is unknown. These conditions can be subdivided into syndromal and non‐syndromal, depending on the existence of a recognizable pattern of minor anomalies and/or malformations, or lack thereof. Seventeen genes have been regionally mapped onto the X chromosome. However, in 14 instances the data were derived from a single family and most lod scores were less than 3.0.
Prevalence of fra(X) and other specific diagnoses in autistic individuals in a Danish County
Authors: Tranebjaerg Lisbeth , Kure P.
Published: June 2005

In a Danish county (the island of Funen) cytogenetic screening for fragile X [fra(X)] of 32 autistic individuals aged 0–23 years showed a prevalence of 2/20 among boys and 0/12 among girls. In both cases additional fra(X) positive relatives were found. In 3 patients other chromosome aberrations were demonstrated and in one female Rett syndrome was diagnosed, initially suspected from observations of her behavior on videotapes. The presence of an underlying cause of autism in 6/32, of the patient group encourages an active search for a specific diagnosis among autistic males and females. Future screening of autistic individuals should include 1) fra(X) search also in females, 2) search for other chromosomal disorders, and 3) observation of behavior, in order to diagnose, i.e., Rett syndrome.
Linkage analysis in a large family with nonspecific X‐linked mental retardation
Authors: Glass I. A. , White E. M. , Pope M. J. , Pirrit L. A. , Cockburn F. , Connor J. M.
Published: June 2005

We report on a large 5‐generation family with “nonspecific” X‐linked mental retardation. Nine living affected males have an IQ between 50 and 70 but have normal stature, facial appearance, and testicular volumes and no other abnormalities. Two obligate carrier females had borderline intellectual abilities and visual‐psychomotor difficulties similar to those seen in affected males. Results of chromosome studies, including fragile X, were normal in males and females. Linkage analysis was undertaken, with 19 X‐specific chromosomal restriction fragment length polymorphisms (RFLPs), giving a maximal LOD score of 1.60 at a 0.10 recombination fraction for F9, suggesting a localization to distal Xq for the mutant gene in this family.
Martin–Bell syndrome segregating in a large kindred with normal transmitting males: Clinical, cytogenetic, and linkage study
Authors: Johnson Virginia P. , Carpenter Nancy J. , Skorey Patricia A.
Published: June 2005

We report on a large kindred with 10 mentally retarded, fra(X) positive males and 2 normal transmitting males. Clinical findings include variable degrees of facial anomalies, macroorchidism, behavioral characteristics, and cognitive deficiencies. The affected grandsons were fra(X) positive while their obligate carrier mothers and transmitting grandfathers were fra(X) negative. DNA‐restriction fragment length polymorphism (RFLP) linkage study was undertaken to find informative markers to identify heterozygotes or hemizygotes. The problems encountered in genetic counselling, by the absence of established criteria for diagnosis, are discussed.
Fragile X checklist
Authors: Hagerman Randi J. , Amiri Khaled , Cronister Amy
Published: June 2005

A 13‐item checklist that combines physical and behavioral traits typical of fragile X [fra(X)] syndrome was evaluated prospectively in the screening of 107 males with mental retardation or severe learning disabilities. The checklist was completed before we obtained cytogenetic results. Fifteen males were fra(X)‐positive and the manifestations that differentiated fra(X)‐positive and fra(X)‐negative patients included perseverative speech, large or prominent ears, large testicles, and tactile defensiveness. The combination of physical and behavioral traits is helpful in suggesting the diagnosis and identifying high‐risk patients. A total score of 16 or higher had a significant yield of fra(X)‐positive patients (≥45%).
Detection of fragile X non‐penetrant males by DNA marker analysis
Authors: Brown W. Ted , Gross Anne , Goonewardena Ponmani , Ferrando Charles , Dobkin Carl , Jenkins Edmund C.
Published: June 2005

Segregation analysis of the fragile‐X [fra(X)] syndrome uncovered an unexpected 20% excess of normal males among sibships by Sherman et al. (Sherman SL, Morton NE, Jacobs PA, Turner G [1984]. Ann Hum Genet 48:21–37; Sherman SL, Jacobs PA, Morton NE, Froster‐Iskenius U, Howard‐Peebles PN, Nielsen KB, Partington MW, Sutherland GR, Turner G, Watson M [1985]: Hum Genet 63:289–299). This result predicts that about 17% (1/6) of normal sons of carrier fra(X) females will be non‐penetrant. A way to test this prediction is by DNA markers. We analyzed DNA samples from 100 families with a set of flanking DNA markers linked to the fra(X) locus. Ten of 51 (19.6%) normal brothers, doubly informative and non‐recombinant for flanking DNA markers, were found to be non‐penetrant males. This result closely confirms the predictions of the segregation analysis indicating that about 1/6 of normal brothers are non‐penetrant carrier males.

The use of DNA markers to identify non‐penetrant brothers and grandfathers can help to clarify the inheritance of the fra(X) mutation and be of considerable clinical usefulness. Using DNA markers, it was possible to study grandparental transmission in 71 of the families. In 39 families, DNA analysis confirmed the apparent pattern of inheritance. In 18 families, the grandparents had a single daughter with affected children. Of these, a new mutation at the time of their daughters conception was possible in 15 and quite likely in 3. In 14 families with 2 or more daughters with affected fra(X) offspring, the grandparents had no affected sons or other relatives known to be positive for fra(X). In 6 of these families, only 2 daughters had affected sons and transmission was found to be from a non‐penetrant grandfather in 3. In the other 8 families, 3 or more daughters had affected sons and the grandfather was found to be a transmitting male in 7. These results have allowed guidelines to be formulated to assist with genetic counseling in the use of DNA markers in detecting non‐penetrant males.
Linkage analysis in the fragile X syndrome using multiple distal Xq polymorphic DNA markers
Authors: Glass I. A. , Pirrit L. A. , White E. M. , Bell M. V. , Davies K. E. , Cockburn F. , Connor J. M.
Published: June 2005

Linkage data using the polymorphic loci F9, DXS105, DXS98, DXS52, DXS15, and F8 and the DNA probe 1A1 are presented from 14 families segregating for fragile X [fra(X)] syndrome. Recombination fractions corresponding to the maximum LOD scores obtained by two‐point linkage analysis suggest that DXS98 (Zmax = 3.23, theta = 0.0) and DXS105 (Zmax = 2.09, theta = 0.0) are the closest markers proximal to FRAXA and that DXS52 is the closest distal marker (Zmax = 3.55, theta = 0.16). FRAXA is located within a 25 cM interval between F9 and DXS52, coincident with DXS98, on multipoint linkage analysis. Phase‐known three way crossover information places F8 outside the cluster (DXS52, DXS15, 1A1). Confidence limits for the markers DXS98 and DXS52 are relatively wide (0.0–0.15 and 0.06–0.31, respectively), but when used in combination with cytogenetic examination offer improved carrier detection in comparison with cytogenetic analysis alone.
DNA‐based genetic testing in fifty fragile X families
Authors: Murphy P. D. , Watson M. S. , Shapiro L. R. , Wilmot P. L. , Breg W. R.
Published: June 2005

During the past 4 years (1985–1989), we have analyzed 171 cases in 50 fragile X [fra(X)] families by DNA linkage methods. Most (140 cases; 81%) were for carrier detection, both female (98 cases; 57%) and male (41 cases; 24%). Women who were obligate carriers of the fra(X) mutation accounted for an additional 6 “prior‐to‐pregnancy” cases. Four pregnancies have subsequently occurred with 3 having been successfully monitored (one male, 2 females). One pregnancy miscarried early prior to testing. Prenatal diagnoses (26 cases; 15%) accounted for the remainder of cases (15 males, 11 females). These will be discussed in the companion paper by Shapiro et al. (Am J Med Genet, 1991).

A diagnosis in the cytogenetically uninformative carrier cases was reached in >75% of analyses with a panel of 5 probes: 3 proximal (F9, DXS105, DXS98) and 2 distal (F8, DXS52). Five additional probes, 3 proximal (DXS10, DXS51, DXS102) and 2 distal (DXS15, DXS33), were used in cases that were resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Given this panel, only 5% of cases did not have any informative markers identified. Thus, molecular methods can provide a useful adjunct to cytogenetic analysis in most situations.

An unusual association between the rare allele (A1) of DXS10 with the X chromosome carrying the fra(X) mutation was observed. This occurred in both male and female carriers in the uppermost generation tested. The basis for this association is uncertain at the present time.
Carrier detection of the fragile X syndrome using flanking loci DXS98, DXS105, and DXS304
Authors: Dahl Niklas , Malmgren Helena , Pettersson Ulf , Holmgren Gösta , Seemanová Eva , Gustavson Karl‐Henrik
Published: June 2005

Diagnosis of the carrier status of the fragile X [fra(X)] syndrome was made in 2 unrelated women who did not express the fragile site. Both were related to several individuals with a typical fra(X) phenotype and the marker X chromosome. A restriction fragment length polymorphism (RFLP) approach was used with probes that flank the fra(X) locus (FRAXA). The loci used for risk calculations of the fra(X) genotype were DXS98 and DXS105 on the centromeric side and a recently characterized locus, DXS304, on the telomeric side. Coincidence correction for the distances between marker loci and FRAXA was made according to the Kosambi function. The DNA marker test gave the risk for one female to be a carrier of 99.7–99.9%. In another family a female was excluded from being a carrier with a probability of >99.7%. The DNA marker U6.2, defining the locus DXS304, has increased the reliability of DNA based diagnosis of carrier status for females‐at‐risk. It is concluded that DNA analysis can serve as a valuable complement to chromosome analysis in families informative for the more closely linked flanking markers.
New polymorphism and a new chromosome breakpoint establish the physical and genetic mapping of DXS369 in the DXS98‐FRAXA Interval
Authors: Oberlé I. , Vincent A. , Abbadi N. , Rousseau F. , Hupkes P. E. , Hors‐Cayla M. C. , Gilgenkrantz S. , Oostra B. A. , Mandel J. L.
Published: June 2005

Recently some of us cloned a new probe RN1 (DXS369), which appears a close marker for the fragile X locus (FRAXA) [Oostra et al.: Genomics 1990]. We present here new evidence for its physical and genetic mapping in the DXS98—FRAXA interval. We used 2 different somatic cell hybrid lines with breakpoints in the Xq27–q28 region: L10B Rea and PeCHN, and we established the order: (DXS105, DXS98)‐L10B Rea‐DXS369‐PeCHN‐ (DXS304, DXS52). We detected an additional TaqI RFLP at the DXS369 locus which increases its informativeness up to 57%. Two point linkage analysis in a large set of families gave high lod scores for the FRAXA‐DXS369 linkage (zΘ = 10.1 at Θ = 0.044) and for DXS369‐DXS304, a marker distal to FRAXA (z = 19.2 at Θ = 0.070). By multipoint analyses we established the localization of DXS369 in the DXS98‐FRAXA interval.

DXS369 is a much closer proximal marker for FRAXA than DXS105 or DXS98 and any new probe mapping between the breakpoints in L10B Rea and PeCHN will be of potential interest as a marker for FRAXA.
Linkage in fragile X families of three distal flanking markers: ST14, DX13, and F8
Authors: Brown W. Ted , Gross Anne C. , Goonewardena Ponmani , Ferrando Charles , Dobkin Carl , Jenkins Edmund C.
Published: June 2005

The use of linked DNA markers and linkage analysis in the fragile X [fra(X)] syndrome allows for improved genetic counseling and prenatal diagnosis. In order to provide the most accurate information, it is important to determine the order and location and position of flanking markers. Conflicting results have been reported for the order of 3 DNA markers distal to the fra(X) locus. We analyzed the linkage relationships of the distal markers ST14 (DXS52), DX13 (DXS15), and F8 (F8C) in 102 fra(X) families. The results indicated that the 3 DNA markers were closely linked to one another and mapped approximately 11 to 15% recombination units away from the fra(X) locus. The most likely order was fra(X)‐DXS52‐DXS15‐F8. The order fra(X)‐DXS52‐F8 and 728 times more likely than the order fra(X)‐F8‐DXS52. One family showed a probable double recombinant: in one individual there was recombination between fra(X)‐DXS52 and between DXS52‐F8. The low probability of this occurring, 0.3%, raises the possibility of an alternate chromosome arrangement or an unusual recombinant mechanism in some individuals.
Linkage relationships between DXS105, DXS98, and other polymorphic DNA markers flanking the fragile X locus
Authors: Carpenter Nancy J. , Thibodeau Stephen N. , Brown W. Ted
Published: June 2005

We report on linkage data between DXS105, DXS98, the locus for the fragile X syndrome (FRAXA), and 3 other polymorphic loci that flank the FRAXA locus. An analysis was undertaken to determine the relative positions of DXS105 and DXS98 and to test the assignment of DXS105 to a location proximal and closely linked to FRAXA. In this study of fragile X fra(X) syndrome families, the DXS105 locus was calculated to be proximal to FRAXA with a maximum lod score of 10.36 at θ = 0.08. DXS105 was also shown to be closely linked to the gene for factor IX (F9)(Ẑ = 11.84 at θ = 0.08) and to DXS98 (Ẑ = 4.91 at θ = 0.04). The order of the loci proximal to FRAXA is most likely centromere‐factor IX‐DXS105‐DXS98‐FRAXA‐telomere. The use of DXS105 and DXS98 in clinical investigations should significantly increase the accuracy of risk assessment in informative fragile X families.
Physical and genetic mapping of the CDR gene with particular reference to its position with respect to the FRAXA site
Authors: Siniscalco Marcello , Oberlé Isabelle , Melis Paola , Alhadeff Becky , Murray Jeff , Filippi Giorgio , Mattioni Tiziana , Chen Yao‐Tseng , Furneaux Henry , Old Lloyd J. , Posner Jerome B.
Published: June 2005

This study narrows down the localization of the gene coding for the cerebellar degeneration‐related protein (CDR 34) to the upper boundary of the FRAU and reports the finding of two common RFLPs respectively identified at an RsaI site flanking the 3′ end of the gene and at a Hincll site flanking its 5′ end. Segregation analysis carried out in the CEPH‐pedigrees for the new CDR/RsaI‐RFLP versus other polymorphic loci of the region has established a tight linkage with the markers DXS105/DX98 and absence of measurable linkage with two clusters of markers respectively located proximally to the FRAXA (F9, DXS102, DXS51, and DXS369) or distally to it (DXS52, DXS304). In addition, two recombinants were found among 23 scorable sibs identified in the Sardinian pedigrees segregating for the Martin‐Bell Syndrome (MBS) and the CDR/RsaI variants. The overall evaluation of the in situ and genetic data reported suggest that the CDR locus 1) is located at the upper boundary of the FRAXA site; 2) is distal to DXS51 and proximal to DXS 389; and 3) segregates in a close linkage association with the loci DXS98 and DXS105 and, to a lesser extent, with the locus for MBS.
Transmission of mental retardation with fragile X site by two normal transmitter brothers
Authors: Pellissier Marie‐Christine , Voelckel Marie‐Antoinette , Piquet Caroline , Mattei Marie‐Geneviève , Mattei Jean‐François
Published: June 2005

We report clinical, chromosomal, and DNA studies in 32 individuals in a family with mental retardation associated with the fragile X chromosome transmitted through 2 normal transmitter brothers.
Polymerase chain reaction detection of the Dde I polymorphism in the factor 9 gene for fragile X linkage analysis
Authors: Dobkin Carl S. , Driscoll M. Catherine , Ferrando Charles
Published: June 2005

We have used the polymerase chain reaction (PCR) to analyze the 50 base pair (bp) insertion/deletion polymorphism in the coagulation factor 9 gene. This procedure is particularly applicable for DNA marker studies in fragile X families. The polymorphism, which can also be detected in Dde I digestions, was detected by the amplification of fragments of 298 and 348 bp. The alleles were distinguished directly by agarose gel electrophoresis. PCR detection of this polymorphism is much simpler, more accurate, and quicker than conventional analysis.