bluuebunny/crossref_metadata_2025 huggingface dataset:
Prevalence study of Prader‐Willi syndrome in North Dakota
Authors: Burd Larry , Vesely Barbara , Martsolf John , Kerbeshian Jacob
Published: June 2005

A prevalence study of Prader‐Willi syndrome (PWS) has been conducted in North Dakota. All pediatricians, neurologists, child psychiatrists, psychologists, and clinical geneticists were surveyed. The state's comprehensive evaluation center, the state hospital, the state institution for the mentally retarded, and group homes for the developmentally disabled, including one for persons with PWS, were also contacted. Seventeen patients were identified, 8 males, 8 females, and one patient whose sex was not specified. This suggests a prevalence rate of 1 per 16,062 in North Dakota.
Lambotte syndrome: Microcephaly, holoprosencephaly, intrauterine growth retardation, facial anomalies, and early lethality—A new sublethal multiple congenital anomaly/mental retardation syndrome in four sibs
Authors: Verloes A. , Dodinval P. , Beco L. , Bonnivert J. , Lambotte C.
Published: June 2005

We report on an Arabic sibship originating from Morocco in which four children manifest an undiagnosed sublethal multiple congenital anomaly/mental retardation (MCA/MR) syndrome of intrauterine growth retardation (IUGR), microcephaly, large soft pinnae, telecanthus or true hypertelorism with squint, flat face, unusual hooked nose, very narrow mouth, retrognathia, and extremely severe neurologic impairment. One child was stillborn. Three others died in a cachectic state during their second year. One child had a severe cerebral malformation compatible with semilobar holoprosencephaly. Other inconstant manifestations are anterior chamber cleavage defect, preaxial polydactyly of feet, interventricular septal defect, and atresia of the external auditory meatus. Autosomal recessive inheritance is likely.
Carrier testing and prenatal diagnosis for hemophilia: Experiences and attitudes of 549 potential and obligate carriers
Authors: Varekamp I. , Suurmeijer Th. P. B. M. , Bröcker‐Vriends A. H. J. T. , van Dijck H. , Smit C. , Rosendaal F. R. , Briët E.
Published: June 2005

Experiences with and attitudes toward carrier testing and prenatal diagnosis were evaluated among 549 potential and obligate carriers of hemophilia. Almost everybody considered carrier testing to be useful. Forty‐nine percent had been tested for carriership, 10% had only received limited information, and 41% had not been tested and had never received information about the heredity of hemophilia. More married women, women with severe hemophilia in their family, and women closely related to a patient with hemophilia had been tested for carriership than others. Lack of information about the probability of carriership for female relatives and a similar ignorance of the possibility of carrier testing were important reasons for not having been tested. Eleven percent of the women with one or more children had undergone prenatal diagnosis in the past. Thirty‐one percent of the study population would favour prenatal diagnosis with the implication of a potential abortion in early pregnancy and half of them would choose this option even in late pregnancy. Most of the women who objected to prenatal diagnosis did so because they did not consider hemophilia to be a sufficiently serious disorder to justify an abortion.
Microphthalmia and chorioretinal lesions in a girl with an Xp22.2‐pter deletion and partial 3p trisomy: Clinical observations relevant to aicardi syndrome gene localization
Authors: Donnenfeld Alan E. , Graham John M. , Packer Roger J. , Aquino Rosaria , Berg Susan Z. , Emanuel Beverly S.
Published: June 2005

We present a 4‐year‐old girl with a maternally derived, unbalanced X;3 translocation resulting in partial Xp monosomy and partial 3p trisomy. She had chorioretinal defects, developmental delay, infantile seizures, and microphthalmia. These findings initially suggested a diagnosis of Aicardi syndrome. However, she had a normal‐appearing corpus callosum on CT and magnetic resonance imaging scans of the brain and her retinal findings were not typical for Aicardi syndrome. This represents the 6th reported example of microphthalmia associated with an Xp22 chromosome abnormality. Four of these individuals also had features suggestive of focal dermal hypoplasia (FDH), which was not evident in our patient. The available evidence supports the hypothesis that gene disruption at Xp22 may lead to findings similar to those seen in Aicardi syndrome and FDH, both of which are believed to be X‐linked dominant male lethal conditions.
Somatic mosaicism at the duchenne locus
Authors: Lebo Roger V. , Olney Richard K. , Golbus Mitchell S.
Published: June 2005

Results of testing a family for carrier status and prenatal diagnosis for Duchenne muscular dystrophy (DMD) are best explained by somatic mosaicism in the maternal grandfather. This genetic situation was identified using segregation analysis of intragenic DNA polymorphisms, a serum creatine phosphokinase assay, and physical examination of the patient. This event at the DMD locus represents one more potential source of error in carrier testing and prenatal diagnosis.
The craniodigital syndrome of Scott: Report of a second family
Authors: Lorenz Peter , Hinkel Georg Klaus , Hoffmann Carola , Rupprecht Edgar
Published: June 2005

We report on a boy with a characteristic combination of facial anomalies, syndactylies of fingers and toes, and mental retardation. Scott et al. (Journal of Pediatrics 78:658–663, 1971) observed 3 brothers with almost identical manifestations. The mother of these patients had bilateral syndactyly of toes 2 and 3. This led the authors to suggest X‐linked inheritance. The mother of our patient also has cutaneous syndactyly between the second and third toes, strengthening the hypothesis of X‐linked inheritance.
Ullrich‐turner syndrome with agenesis of the corpus callosum
Authors: Kimura Masahiko , Nakajima Masako , Yoshino Kunio
Published: June 2005

We report on a 19‐year‐old woman with 45,X Ullrich‐Turner syndrome who was severely mentally retarded and had hypotonia. Computer tomography (CT) scan showed agenesis of the corpus callosum. There have been few reports of gross developmental central nervous system (CNS) abnormalities in Ullrich‐Turner syndrome. Only one case of Ullrich‐Turner syndrome with agenesis of the corpus callosum has been reported. The high prenatal lethality of Ullrich‐Turner syndrome may mask a CNS abnormality.
Chromosome lesions which could be interpreted as “fragile sites” on the distal end of Xq
Authors: Butler Merlin G. , Allen G. Andrew , Haynes Judy L. , Clark Samuel J.
Published: June 2005

Chromosome lesions which could be interpreted as “fragile sites” on the distal end of the long arm of the X chromosome were identified during a cytogenetic study of 160 mentally retarded adult males with no apparent cause of their mental retardation and one normal adult female with a family history of fra (X) syndrome. Peripheral blood samples were cultured in either M199 or RPMI 1640 medium with FUdR or BrdU. Metaphases were examined for chromosome lesions or fragile sites on the distal end of Xq and 3 distinct sites were observed: Xq26, Xq27.2, and Xq27.3. Other chromosome lesions at Xq28 were observed and interpreted as nonspecific telomeric structural changes. Chromosome lesions were observed in cells from 14 of the 161 individuals. These included: 5 patients with an Xq26 site, 2 with the recently reported Xq27.2 site, 4 with the Xq27.3 site (characteristic of the fra (X) syndrome), 2 with nonspecific telomeric structural changes, and one individual with 2 lesions (a nonspecific telomeric structural change and an Xq26 site). Additional research is necessary to determine the frequency and clinical significance, if any, of lesions occurring in this region of the X chromosome and to distinguish among heritable fragile sites, constitutive fragile sites, and nonspecific telomeric structural changes.
True precocious puberty in a girl with the fragile X syndrome
Authors: Moore Patrick S. J. , Chudley Albert E. , Winter Jeremy S. D.
Published: June 2005

A 2.8‐year‐old girl was investigated for early breast development and delayed psychomotor development. Chromosome analysis showed a fragile site at Xq27. Skeletal maturation was advanced. Computerized tomography of the head was normal. Pelvic ultrasonography showed ovaries and uterus enlarged for age. Basal serum gonadotropins were within the normal prepubertal range, but serum luteinizing hormone (LH) and follicle‐stimulating hormone (FSH) levels rose during sleep and following stimulation by gonadotropin‐releasing hormone (GnRH), consistent with true precocious puberty. The occurrence of precocious puberty in this girl, and macro‐orchidism in affected males may be a reflection of an underlying disturbance of hypothalamic‐pituitary‐gonadal function in fragile X patients.
Interpretation of chromosome mosaicism and discrepancies in chorionic villi studies
Authors: Sachs Eva S. , Jahoda Milena G. J. , Los Frans J. , Pijpers Leen , Reuss Annette , Wladimiroff Juriy W.
Published: June 2005

In 3,000 chorionic villi studies (CVS) 33 cases of mosaicism and 7 false‐positive cell lines in all cells were seen. The mosaic cell lines were caused by aneuploidy of autosomes (13x), sex chromosomes (9x), and structural anomalies (11x). Mosaics of fetal origin were only 4 cases of trisomy 21 and one 47,XXY mosaic. In 7 cases abnormal karyotype of non‐fetal origin was seen in all cells in direct studies, including trisomy 16 (3x) and trisomy 18 (2x). The combined use of direct CVS and cell cultures always uncovered the non‐fetal origin of chromosome abnormalities and the study of cultured cells in all cases could have prevented 5 terminations. Complete follow‐up studies demonstrated no false‐negative results. Therefore, CVS can be nearly 100% accurate when both direct studies and cultures are examined in cases of mosaicism and other cell lines of possible non‐fetal origin, such as trisomy 16, trisomy 18, translocation (21;21), and 45,X cells.
Jeune syndrome associated with cystinuria: Report of two sisters
Authors: Rinaldi S. , Dionisi‐Vici C. , Goffredo B. , Dallapiccola B. , Rizzoni G.
Published: June 2005

Jeune syndrome is generally lethal in the first months of life. Surviving patients develop progressive renal failure and hepatic fibrosis. We describe 2 sisters, aged 7 and 2 years, respectively, who had Jeune syndrome associated with cystinuria. To our knowledge, this is the first reported association of these 2 autosomal recessive disorders.
Nonreciprocal and jumping translocations of 15q1→qter in Prader‐Willi syndrome
Authors: Rivera H. , Zuffardi O. , Gargantini L.
Published: June 2005

We analyzed 33 cases of Prader‐Willi syndrome (PWS) (including 2 personal observations) with translocations of 15q1 → qter onto the terminals of different, apparently whole chromosomes. In all but one of the 23 informative cases the translocations was de novo. Thirty of the patients were unbalanced and 27 had a 45‐chromosome constitution compatible with a 3:1 segregation. One balanced and 2 unbalanced translocations were jumping ones. The possible existence of actual non‐reciporcal translocations in man is indicated by the following considerations about these and other PWS‐associated rearrangements: (1) The observed excess of de novo translocations; (2) the relatively frequent familial occurrence of reciprocal 15q translocations; (3) the concurrence in 3 terminal translocation cases of an idic (15); (4) the visualization of jumping terminal translocations as simple transpositions rather than as successive reciprocal exchanges; (5) the predominance of true isodicentrics in PWS patients with extra inv dup(15) chromosomes; and (6) the rarity of extra derivatives resulting in 15q proximal tertiary trisomy. Additional findings in the present series were normal parental age in the de novo 45‐chromosome cases, an apparently random distribution of telomeric breakpoints, and the occurrence of different breakpoints within the 15q1 region.
Clonal lines of aneuploid cells in Rothmund‐Thomson syndrome
Authors: Der Kaloustian Vazken M. , McGill James J. , Vekemans Michel , Kopelman Hinda R.
Published: June 2005

We report on a 21‐month‐old white boy with the Rothmund‐Thomson syndrome. The karyotype on fibroblasts from an area of skin with poikiloderma showed the 46,XY,17+der(17),t(2;17)(q11;p13) pattern. Karyotype on fibroblasts from normal skin showed two different abnormal patterns: 47,XY,+8 and 47,XY,+i(2q). His lymphocytes had a normal 46,XY pattern.

These findings indicate in vitro abnormalities. They are explained by a degree of chromosomal instability.
Cerebral palsy in multiple births in Western Australia: Genetic aspects
Authors: Petterson Beverly , Stanley Fiona , Henderson Diane
Published: June 2005

A study of cerebral palsy in multiple births was undertaken to test genetic involvement and assess the impact of the special conditions of pregnancy and parturition in these cases.

Complete ascertainment of cerebral palsy in multiple gestations that occurred in Western Australia between 1956 and 1985 was obtained from the Western Australian Cerebral Palsy Register. There were 74 twins and 5 triplets.

Data on sex, birth order, motor handicap, outcome in co‐twins and triplets, zygosity, and pedigree information was obtained from the Register, hospital records, and, where possible, by interview of the parent(s) of the propositi.

There was a significantly higher (P = 0.0026) concordance rate in MZ than in DZ twin pairs. However, pedigree studies showed no other relatives with a motor handicap similar to that of the propositi. This is consistent with a multifactorial cause in at least some of the cases.

The sex ratio of affected twins was found to be 2.1 compared to 1.3 for singletons and all 5 affected triplets were boys. The trend of increasing sex ratio with increasing plurality was significant at the 1% level.
Agenesis or hypoplasia of major salivary and lacrimal glands
Authors: Milunsky Jeffrey M. , Lee Victor W. , Siegel Benjamin S. , Milunsky Aubrey
Published: June 2005

We described a young man with almost total absence of the parotid glands, hypoplasia of both lacrimal glands, marked hypofunction of both submandibular glands, and left nasolacrimal duct atresia. Lack of tearing, severe dental caries, and conjunctival scarring following chronic xerophthalmia and conjunctivitis serve to alert pediatricians to this autosomal dominant disorder with considerable variation in expressivity.
Tissue limited mosaicism in a patient with tetrasomy 9p
Authors: Papenhausen Peter , Riscile Gisele , Miller Karen , Kousseff Boris , Tedesco Thomas
Published: June 2005

Cytogenetic analysis of an abnormal newborn girl showed an extra chromosome with the characteristics of an isodicentric 9p chromosome [idic (9)(pter→q12→pter)] in 98% of peripheral lymphocyte metaphases examined. This cytogenetic interpretation was substantiated by quantitative measurement of erythrocyte galactose‐1‐P‐uridyltransferase (GALT) activity, which is consistent with the expression of 4 normal GALT genes. Cytogenetic results from skin fibroblasts showed mosaicism with only 11% of the metaphases having the extra chromosome. Selective genetic pressure based on a functional disadvantage of tetrasomy 9p in the skin is proposed. The in vivo establishment of cytogenetically normal cells in various tissues may be necessary for in utero survival of tetrasomy 9p infants.
Thymic‐renal‐anal‐lung dysplasia in sibs: A new autosomal recessive error of early morphogenesis
Authors: Rudd Noreen L. , Curry Cynthia , Chen Karl T. K. , Capusten Bernice , Trevenen Cynthia L.
Published: June 2005

We report on 3 sisters with a syndrome of unilobed or absent thymus, renal and ureter agenesis/dysgenesis, and intrauterine growth retardation (IUGR). Two of the 3 infants had a unilobed lung and imperforate anus. Recurrence was detected prenatally by the presence of progressive oligohydramnios and IUGR, a unilateral echogenic cystic mass in the renal fossa, and low amniotic fluid disaccharidases in association with an imperforate anus. Several genetic mechanisms can be invoked to explain this occurrence including autosomal recessive inheritance and an unrecognized chromosome imbalance.
“C” trigonocephaly syndrome: Clinical variability and possibility of surgical treatment
Authors: Lalatta F. , Bagozzi D. Clerici , Salmoiraghi M. G. , Tagliabue P. , Tischer C. , Zollino M. , Di Rocco C. , Neri G. , Opitz J. M.
Published: June 2005

We report on 3 new cases of C trigonocephaly syndrome. In addition to the findings characteristic of this condition, one of the patients also had a large omphalocele. This patient was referred from a suburban hospital with a diagnosis of Down syndrome, stressing the fact that C syndrome is still under‐recognized and underdiagnosed. Another patient was diagnosed at birth and immediately submitted to craniosynostectomy. A second operation was performed 7 months later resulting in normal brain growth and close to normal psychomotor development at 3 years, in contrast to the third patient, who was not treated surgically and was severely retarded at 4 years.
Phenotypic overlap of Ehlers‐Danlos syndrome types IV and VIII
Authors: Hartsfield Jr. James K. , Kousseff Boris G.
Published: June 2005

An 18‐year‐old Caucasian woman has been followed since age 12 years for Ehlers‐Danlos syndrome (EDS) with easy bruisability and “cigarette paper scars.” Her chief complaint at age 17 years was tooth mobility, especially in the anterior mandible, necessitating the removal of the four incisors. Initial biochemical analysis of cultured skin fibroblasts indicated the presence of pepsin‐sensitive type III collagen. Subsequent analysis of cultured skin fibroblasts by the same laboratory and another laboratory found no abnormality in the type III collagen with or without protease treatment. This is in distinction to the finding of abnormal type III collagen in the only two reported patients with EDS and early‐onset periodontitis who have had collagen analyses. One of them was diagnosed as EDS type IV and the other as EDS type VIII, although the defects of type III collagen were consistent with EDS type IV. The defect in type III collagen in some patients with early periodontitis and the considerable overlap of the clinical manifestations of EDS types IV and VIII point out the need for further studies of collagen formation and maturation in any patient who has early periodontitis and who has been classified with EDS type IV or VIII.
A child with multiple congenital anomalies and karyotype 46,XY,del(14)(q31q32.3): Further delineation of chromosome 14 interstitial deletion syndrome
Authors: Gorski Jerome L. , Uhlmann Wendy R. , Glover Thomas W.
Published: June 2005

We report on an infant with a multiple congenital anomaly syndrome and severe developmental delay in association with a previously undescribed de novo interstitial deletion of chromosome 14 [karyotype: 46,XY,del(14) (q31q32.3)]. Comparison of the presented patient with previously reported cases of interstitial and terminal chromosome 14q deletions provides a group of patients monosomic for various overlapping portions of the distal half of chromosome 14q and suggests a limited similarity in phenotype among patients with common deleted 14q segments. All patients with distal 14q deletions were developmentally delayed, most were microcephalic and failed to thrive. Most of the patient's anomalies were limited to the face and head. Few major internal congenital anomalies were observed. These comparisons serve to further clarify possible associations of subchromosomal aberrations with specific phenotypes.
Terminal deletion 6P23: A case report
Authors: Kormann‐Bortolotto M. H. , Farah L. M. S. , Soares D. , Corbani M. , Müller R. , Adell A. C. A.
Published: June 2005

We report on a girl with cleft lip and cleft palate, antimongoloid slant of the palpebral fissures, umbilical hernia, skeletal anomalies, partial syndactyly, hypertonia with increased deep tendon reflexes, psychomotor and growth retardation, and other congenital anomalies. Cytogenetic studies demonstrated a 46,XX,del(6)(qter→p23:) chromosome constitution.
Aminopterin‐like syndrome sine aminopterin associated with translocation involving chromosomes 5 and 10
Authors: Chen Moy‐Fong , Vekemans Michel , Meagher‐Villemure K. , Outerbridge Eugene , Fraser F. Clarke , Der Kaloustian Vazken M.
Published: June 2005

We studied a baby born with physical features suggestive of the aminopterin syndrome, but without exposure of the mother to aminopterin during pregnancy.

G‐banded chromosomes from peripheral blood lymphocytes had a normal 46,XX pattern. However, in 50 skin fibroblasts there was a normal female karyotype in 5 cells and 45 cells showed an apparently balanced reciprocal translocation involving the long arm of chromosome 5 (band q35) and the long arm of chromosome 10 (band q22). The relation of this mosaicism to the abnormal phenotype is unclear.
Dermatoglyphics in the identification of women either with or at risk for breast cancer
Authors: Seltzer Murray H. , Plato Chris C. , Fox Kathleen M.
Published: June 2005

Fingerprints and palm prints were studied in 78 breast cancer patients, 391 patients at increased risk for developing breast cancer, and 64 control patients for the purpose of finding a pattern that would identify those women with breast cancer or those who are predisposed to its development.

A pattern of 6 or more digital whorls was identified more frequently in women with breast cancer than in those without the disease (P<0.01). This finding was independent of known risk factors for breast cancer and was present in 28% of the cancer patients. No correlation was noticed between palm prints and breast cancer.

The positive predictive value of 6 or more digital whorls was comparable to that of mammography and that of breast biopsy. With increasing age there was an increase in the positive predictive value associated with 6 or more digital whorls.

It is concluded that digital dermatoglyphics may have a future role in identifying women either with or at increased risk for breast cancer such that either risk reduction measures or earlier therapy may be instituted.
Concurrence of robinow syndrome and Crigler‐Najar syndrome in two offspring of first cousins
Authors: Nazer Hisham , Gunasekaran Thirumazhisai S. , Sakati Nadia A. , Nyhan William L.
Published: June 2005

Robinow syndrome and Crigler‐Najar syndrome were encountered in 2 Saudi offspring of first cousins. Both died at age 4 months. The parents lost 2 previous children at age 2 months with progressive jaundice but without fetal facial characteristics.
Satisfaction with genetic counseling: Dimensions and measurement
Authors: Shiloh Shoshana , Avdor Orit , Goodman Richard M.
Published: June 2005

Patient satisfaction has become a significant issue in evaluating medical care, although it has been largely neglected in genetic counseling. A 32‐item questionnaire was designed to examine patient satisfaction and was administered to 76 clients in a genetic counseling center, and 56 parents attending a pediatric outpatient clinic (the control group). Factor analysis showed 3 dimensions to satisfaction with genetic counseling: instrumental, affective, and procedural. The general level of satisfaction was found to be lower in the genetic counseling group than in the control group. This finding was interpreted as expressing basic properties of genetic counseling. The most important determinant of satisfaction with the content of information provided in counseling. Some affective and procedural aspects of genetic clients' general sense of satisfaction, as compared to the control subjects.
Tetralogy of Fallot in three sibs
Authors: Pankau Rainer , Siekmeyer Werner , Stoffregen Regina
Published: June 2005

We report on three sibs (2 boys, one girl) with tetralogy of Fallot from non‐consanguineous parents. The first child died during corrective surgery in 1972 from irreversible right ventricular failure. Corrective surgery was successful in the 2nd son and the daughter. The occurrance of tetralogy of Fallot in 3 sibs suggests a recessive gene.
The syndrome of Möbius sequence, peripheral neuropathy, and hypogonadotropic hypogonadism
Authors: Kawai Masahiko , Momoi Toru , Fujii Tatsuya , Nakano Shozo , Itagaki Yasuko , Mikawa Haruki
Published: June 2005

We report on a 17‐year‐old Japanese boy with Möbius sequence, peripheral neuropathy, and hypogonadotropic hypogonadism, the fourth such case known to us. The association of peripheral neuropathy and hypogonadotropic hypogonadism in Möbius sequence seems to be more than coincidence. Pulsatile gonadotropin‐releasing hormone administration for 3 months showed the effectiveness of this treatment for this patient.
Low molecular weight urinary peptides in ceroid‐lipofuscinoses: Potential biochemical markers for the juvenile subtype
Authors: LaBadie Gundula U. , Pullarkat Raju K.
Published: June 2005

Urine from patients with classical and atypical forms of juvenile ceroid‐lipofuscinosis (CL) was analyzed for the presence of diseasespecific peptides. Two distinct peptide paterns were recognized on lithium dodecyl sulfate polyacrylamide gel electrophoresis in classical juvenile CL Patients. Pattern 1 consisted of a single, intensely staining peptide of apparent Mr 2,000 and up to 4 heterogeneous, weakly staining peptides between 2,500 and 6,300 Mr. This peptide pattern was not seen in over 30 samples from patients with other neurodegenerative disorders, nor in normal control individuals. Reduced amounts of the 2,000 Mr Peptide were seen in 2 of 3 female heterozygotes whose children had the peptide pattern 1. The presence of large amounts of the 2,000 Mr peptide in urine extracts made patient identification unequivocal. Pattern 2 had 2 to 3 intensely staining peptide of 3,800, 5,000 and 7,000 Mr, a variable number of minor bands, and diffuse staining above 7,000 and below 3,800 Mr. Parents had 2 to 3 weakly staining peptides with molecular weights similar to the major bands seen in the patients. No consistent peptide pattern was seen in 8 patients with atypical CL. Late infantile CL patients had no or very small amounts of low Mr urinary peptides.

The urinary components stained well with silver, poorly with coomassie Blue, and were digested by a nuclease‐free protease, as expected for protein. They were distinctly different from the peptides isolated from ovine CL tissues. Amino acid composition analysis showed a predominantly normal spectrum of amino acids.

Patients could not be consistently distinguished from individuals with other neurodegenerative disorders based on urinary dolichol levels. However, 10 of 11 patients with classical juvenile CL could be diagnosed based on their urinary peptide patterns. Heterogeneity in the number, amount, and Mr of urinary peptides was observed within and between subtypes and sibships. It was concluded that demonstration of specific low Mr peptide pattern 1 and the more heterogeneous peptide pattern 2 in urines may aid in the diagnosis of juvenile CL.
Antecubital pterygium and cleft lip/palate presenting as signs of the nail‐patella syndrome: Report of a Brazilian family
Authors: Richieri‐Costa A.
Published: June 2005

We report on 4 persons in a 3‐generation Brazilian family presenting the nail‐patella syndrome. Cleft lip/palate in one patient and antecubital pterygium in 3 of the reported patients are unusual findings related to this condition.
Pseudoxanthoma elasticum: Similar autosomal recessive subtype in Belgian and Afrikaner families
Authors: Paepe Anne De , Viljoen Denis , Matton Maria , Beighton Peter , Lenaerts Veronique , Vossaert Katrien , Bie Sylvia De , Voet Dirk , De Laey Jean‐Jacques , Kint André
Published: June 2005

A multidisciplinary survey of the clinical and genetic characteristics of 26 Belgian and 32 Afrikaner families with biopsy‐proven pseudoxanthoma elasticum (PXE) was undertaken. The major PXE phenotype emerging from this study is very similar in both patient groups and is characterized by severe ophthalmologic manifestations with variable, mild cutaneous and vascular symptoms. In the families with more than one affected relative, segregation analysis is compatible with autosomal recessive inheritance in both groups. It is suggested that the PXE phenotype of these Belgian and Afrikaner patients is distinct from the other recognized PXE subtypes. The phenotypic resemblance in both patient groups raises the question whether a similar genetic mechanism is involved.
Epiphyseal stippling in acrodysostosis
Authors: Viljoen Denis , Beighton Peter
Published: June 2005

Widespread epiphyseal stippling was demonstrated radiologically during the early months of life in 7 children with acrodysostosis. This finding, which does not seem to have been previously documented in this disorder, is important in the differential diagnosis.
Fucosidosis revisited: A review of 77 patients
Authors: Willems Patrick J. , Gatti Rosanna , Darby John K. , Romeo Giovanni , Durand Paolo , Dumon Jan E. , O'Brien John S.
Published: June 2005

Fucosidosis is a rare, autosomal recessive, lysosomal storage disorder caused by a severe deficiency of alpha‐L‐fucosidase in all tissues. We have conducted a review of fucosidosis, compiling data from published reports and an international questionnaire survey. Seventy‐seven patients affected with fucosidosis of which 19 had not been reported before have been identified. A major aim of the present study was to define the natural history of fucosidosis.

The clinical picture of fucosidosis consists of progressive mental (95%) and motor (87%) deterioration, coarse facies (79%), growth retardation (78%), recurrent infections (78%), dysostosis multiplex (58%), angiokeratoma corporis diffusum (52%), visceromegaly (44%), and seizures (38%). Whereas the original fucosidosis patients described by Durand et al. (Pediatr 75:665–674, 1969) were decerebrate and died before age 5 years, most fucosidosis patients have a slower course of degeneration. Mortality before age 5 years was observed in only 7 patients (9%), whereas 36 patients (64%) reached the second decade. We did not find evidence for the existence of clinical heterogeneity with a rapidly progressive type I and a slowly progressive type II fucosidosis as suggested in the literature. Instead, there seems to exist a wide continuous clinical spectrum.

At the biochemical level no heterogeneity in residual fucosidase enzyme activity or crossreacting immunoreactive fucosidase protein was observed. At the DNA level at least 4 different mutations must be responsible for fucosidosis. These genotypic differences however do not explain the observed phenotypic differences.
New X‐linked mental retardation disorder with Dandy‐Walker malformation, basal ganglia disease, and seizures
Authors: Pettigrew Anjana L. , Jackson Laird G. , Ledbetter David H.
Published: June 2005

We report on a 4 generation family of individuals with an X‐linked form of mental retardation involving 9 affected males and 5 obligate carrier females. Key manifestations include severe mental retardation, early hypotonia with progression to spasticity and contractures, choreoathetosis, seizures, presence of a long, narrow face with coarse features, cystic enlargement of the fourth ventricle with cerebellar hypoplasia (Dandy‐Walker malformation), and iron accumulation in the basal ganglia with neuroaxonal dystrophy similar to Hallervorden‐Spatz disease. Of the 5 known heterozygotes, 3 are dull intellectually, and one of the 3 developed a “presenile dementia.” At autopsy she had iron deposition and neuroaxonal dystrophy in the basal ganglia and atrophy of the cerebral cortex. Although the clinical findings among relatives are variable, we conclude that this is a distinct, previously unrecognized X‐linked mental retardation syndrome.
Fragile X screening program in New York State
Authors: Nolin Sarah L. , Snider Donald A. , Jenkins Edmund C. , Brown W. Ted , Krawczun Michael , Stetka Daniel , Houck George , Dobkin Carl S. , Strong Gloria , Smith‐Dobransky Gail , Victor Arnold , Hughes Kevin , Kimpton Donna , Little Anne , Nagaraja U. , Kenefick Barbara , Sullivan Connie
Published: June 2005

Most fragile X [fra(X)] males in New York State have not been identified. Hence, a large number of female relatives are unaware of their risks for having an affected child. A program was established in New York State in 1987 to screen for the fra(X) syndrome in mentally retarded males with living relatives. The goal of the program is to identify affected males and inform their families about the diagnosis. In this way relatives would be able to assess their risks for having a fra(X) male.

In order to identify the males a screening form was developed to assess 10 features which included physical characteristics, behavior, and family history. Males who exhibited at least 5 of these manifestations were selected for cytogenetic analysis. Any male who had macroorchidism or a family history of mental retardation was also included. A total of 995 males have been screened of which 352 (35%) were selected for cytogenetic analyses. Seventeen (10.5%) of the 161 completed studies were positive for fra(X). A large number of possible female carriers were identified in the families of the propositi.

This program identifies fra(X) males in a population of the mentally retarded for whom there had been no previous diagnosis. By using a two‐step procedure, it is possible to screen a large population of the mentally retarded for fra(X) without testing each male cytogenetically.
Clinical screening score for the fragile X (Martin‐Bell) syndrome
Authors: Laing Sue , Partington Michael , Robinson Hazel , Turner Gillian
Published: June 2005

A clinical score based on the manifestations of the fragile(X) syndrome has been formulated and applied to all individuals included in a fragile(X) case finding program in New South Wales. The total score can vary from 0 to 10. Individuals are scored 0, 1, or 2 in each of 5 categories considered indicative of the fragile(X) phenotype: family history of intellectual handicap, face length, ear configuration, personality, and body habitus.

In a study of 1,206 individuals where the clinical scores were prospective (i.e., they had been given before the cytogenetic results were known) the percentage of those with the fragile(X) increased from 0.6% of those with scores of 4 or less to 14.6% with scores 5–7 and to 67% of those with scores 8–10.

We have found the score simple to use in the circumstances where screening takes place (sheltered workshops and schools) and have reduced the number of individuals tested cytogenetically by 45%.
Multipoint linkage analysis of DXS369 and DXS304 in fragile X families
Authors: van Oost B. A. , Smits A. , Dreesen J. C. F. M. , Smeets D. , Perdon L. , van Bennekom C. A. , Dahl N. , Bakker E. , Oostra B. A.
Published: June 2005

Diagnosis of carriers of the fragile‐X mental retardation gene is hampered by the paucity of tightly linked DNA markers. Recently, 2 new DNA markers RN1 (DXS369) and U6.2 (DXS304) have become available. Both markers are tightly linked to the fragile‐X locus, but their location relative to the fragile site was not known with certainty. We have tested these new markers in a multipoint linkage analysis of 26 fragile‐X families typed for DXS105 as a proximal marker and DXS52 as a distal marker. Our results establish the order DXS105‐DXS369‐fra(X)‐DXS304‐DXS52, which is in agreement with physical mapping results.
Mapping of a new RFLP marker RN1 (DXS369) close to the fragile site FRAXA on Xq27–q28
Authors: Oostra B. A. , Majoor‐Krakauer D. F. , van Hemel J. O. , Bakker E. , Callen D. F. , Schmidt M. , van Oost B. A.
Published: June 2005

A new polymorphic DNA marker RN1, defining locus DXS369, was recently isolated. Using different somatic cell hybrids, RN1 was mapped between markers 4D‐8 and U6.2. We have narrowed the localization of RN1 to the region between 4D‐8 and FRAXA by genetic mapping in fragile X [fra(X)] families. Combined with information from other reports, the following order of loci on Xq27–q28 is suggested: cen‐F9‐(DXS105‐DXS152)‐DXS98‐DXS369‐FRAXA‐DXS304‐(DXS52‐DXS15‐F8)‐tel. The locus DXS369 is closely linked to FRAXA, with a peak lodscore of 18.5 at a recombination fraction of 0.05. Therefore, RN1 is a useful probe for carrier detection and prenatal diagnosis in fra(X) families.
Fragile X families in a Northern Swedish County: A genealogical study of possibly affected individuals in the nineteenth century
Authors: Drugge Ulf , Blomquist Hans K:son , Gustavson Karl‐Henrik , Holmgren Gösta
Published: June 2005

Most studies of fragile X fra(X)I families are able to document mental impairment only by family history. Using Swedish historical archives and the unique parish catechetical meeting records it is possible to document qualitative phenomena such as literacy for over 100 years. In this way it was possible to identify 7 individuals with mental retardation living in the nineteenth century in an earlier published fra(X) pedigree. Four of them were female. At the present time another 4 severely mentally retarded females with the fra(X) syndrome have been diagnosed in this family. The high prevalence of mentally retarded females might indicate a variant form of the fra(X) syndrome in this family.
Fragile X syndrome in an extended family with special reference to an affected male with Klinefelter Syndrome
Authors: Voelckel Marie‐Antoinette , Pellissier Marie‐Christine , Piquet Caroline , N'Guyen Catherine , Boccaccio Irène , Philip Nicole , Mattei Jean‐François
Published: June 2005

We report on a large family (4 generations), with 77 studied individuals, 9 mentally retarded males, and one affected female with fragile X syndrome [fra(X)]. The analysis of 6 flanking polymorphic DNA markers showed that the affection is transmitted, through the carrier daughters to the grandsons and the greatgrandsons and that the greatgrandfather is a transmitting male. This observation led us to question the importance of these clinically normal males, who are nonexpressing carriers and termed transmitting males. One propositus, described as a mentally retarded young man, had inherited identical restriction polymorphisms from his mother. Chromosome analysis showed a Klinefelter syndrome, with a fragile site in 18% of the cells leading to the conclusion that the nondisjunction occurred at the first stage of the maternal meiosis.
Collaborative prospective study of the fragile X syndrome: Request for participation
Authors: Sherman Stephanie L.
Published: June 2005

A collaborative prospective study of the fragile X syndrome (fra[X]) has been initiated to refine the estimates of the recurrence risks based on the phenotype of the mother and the family history of the syndrome. The basic unit of data consists of the description of the pregnancy outcome of women known to carry the fra(X) mutation or who are mothers of a fra(X)‐positive son. Pregnancy outcome includes both prenatal diagnoses and liveborns. The prospective nature of the data eliminates problems of ascertainment and thereby provides more accurate estimates. The specific aims of the study are both clinically and research oriented: (1) refine the estimates of recurrent risks based on the phenotype of the mother and on family history for use in genetic counseling; (2) determine if recurrence risks depend on the phenotype of the carrier parent; (3) determine if a proportion of affected individuals is due to new mutations; and (4) determine the reproductive fitness of fra(X) carriers. This paper describes the rationale behind this study, the data to be collected, and the sample sizes necessary to test hypotheses. Most importantly, participation in this collaborative study is requested from all professionals who work with the fra(X) syndrome.
Genetic and other factors that contribute to variability in cytogenetic expression in fragile X males
Authors: Fisch Gene S. , Silverman Wayne , Jenkins Edmund C.
Published: June 2005

Variability in cytogenetic expression of fragile X has been observed by many investigators. One recent study of families of fragile X brothers concluded that frequency of expression was almost completely controlled by genetic factors. We investigated the extent of genetic control over frequency of expression by evaluating fragile X families from 3 different sources using hierarchal analysis of variance model to calculate the intraclass correlation and the index of heritability, h2. Proportion of variance attributable to families was computed from 2 estimation procedures: (1) a least squares method and (2) a maximum likelihood technique. Results were comparable with one another and indicated that, although genetic factors were significant, differences between laboratories contributed a larger proportion to the total estimated variance. These results partly confirmed previous findings but indicated that the degree of genetic control over the proportion of affected cells was lower than recently suggested.
X chromosome inactivation in fibroblasts of mentally retarded female carriers of the fragile site Xq27.3: Application of the probe M27β to evaluate X inactivation status
Authors: Schmidt Malgorzata , Du Sart Desirée , Kalitsis Paul , Fraser Neil , Leversha Margaret , Voullaire Lucille , Foster Dean , Davies Julie , Hills Louise , Petrovic Vida , Hutchinson Rhonda
Published: June 2005

Over 30% of female carriers of the fragile X [fra(X)] syndrome are clinically affected. A nonrandom X chromosome inactivation in these cases could be a plausible explanation. A review of previous studies addressing this question showed inconclusive results; thus, we analysed the X inactivation pattern in fibroblasts of 4 unrelated, mentally retarded fra(X) carriers with a high expression of the fragile site Xq27.3. Using Southern analysis with a highly polymorphic probe M27β that recognizes methylation differences between the active and inactive X chromosome we found a 50/50 inactivation pattern in 2 cases and skewed patterns in the other 2. As biased patterns were also observed in control females we conclude that at present no evidence exists for a nonrandom X chromosome inactivation in the fra(X) syndrome in females.
Transformation and establishment of fragile X cell lines from amniocytes
Authors: Jenkins Lauren S. , Gruenert Dieter C. , Jenkins Edmund C. , Schonberg Steven A.
Published: June 2005

Fragile X [fra(X)] cell lines have been established from an expressing 46, XX amniocyte culture. The amniocyte cells were transformed by the addition of an origin defective pSV40 vector. Fra(X) expression was observed at a frequency of 3% in the parental amniocyte cell line, and the transformed clones expressed the fra(X) site at a frequency of 9–13%. These cell lines maintain the cytogenetic phenotype and can serve as positive controls for testing the efficacy of the inducing systems during prenatal diagnostic studies.
Endoreduplication and polyploidy in fragile X cells induced by methotrexate and fluorodeoxyuridine: Implications for diagnosis
Authors: Kimchi‐Sarfaty C. , Goitein R. , Kerem B. , Werner M. , Meidan B. , Schaap T.
Published: June 2005

Lymphoblastoid cell lines from fragile X patients and amniotic cells from fragile X embryos, when cultured with methotrexate (MTX) or fluorodeoxyuridine (FUdR), showed a significant increase in endoreduplication and polyploidy. This phenomenon was not observed in fragile X lymphocytes or in lymphoblastoid cell lines and amniotic cells of normal control individuals. The relationship between the inducible fragile site at Xq27.3 and the inducible endoreduplication is discussed. The induction of endoreduplication and polyploidy in fragile X lymphoblasts and amniocytes is evaluated as a possible diagnostic test.
Autosomal folate sensitive fragile sites in normal and mentally retarded individuals in Greece
Authors: Mavrou Ariadni , Syrrou Maria , Tsenghi Christine , Metaxotou Catherine
Published: June 2005

The frequencies of autosomal folate sensitive fragile sites were compared in populations of mentally retarded fra(X) negative (N = 220) and normal children (N = 76) in Greece. In addition, the frequency of autosomal fragile sites was studied in 20 known fra(X) children in order to test if the fra(X) syndrome is associated with general chromosome instability.

The frequencies of both common and rare autosomal fragile sites did not differ significantly between the mentally retarded and the normal children, although the rate of expression was considerably higher in the retarded group. Autosomal fragile sites were not increased in the fra(X) patients. Fra(3)(p14) was by far the most frequent one in all groups. The frequency of fra(6)(q26) was found to be considerably higher among the mentally retarded children, this difference being almost statistically significant. Further cytogenetic studies of normal and retarded individuals are required in order to elucidate this point further.
Origin of the supernumerary X chromosome in a patient with fragile X and Klinefelter syndrome
Authors: Kupke Kenneth G. , Lee Soreng A. , Müller Ulrich
Published: June 2005

We report on a 10‐year‐old patient with the fragile X [fra(X)] syndrome and a 47, XXY karyotype. He had Martin‐Bell syndrome, including typical craniofacial findings and mental retardation. The fra(X) was detected on both X chromosomes of the patient in 8% of the metaphases examined. DNA analysis using X chromosome sequences from the pericentromeric region and from distal Xq suggests that the patient is homozygous at the fra(X) locus due to maternal nondisjunction during meiosis II.
How can the frequency of false‐negative findings in prenatal diagnoses of fra(X) be reduced: Experience with first trimester chorionic Villi sampling
Authors: Kennerknecht Ingo , Barbi Gotthold , Dahl Niklas , Steinbach Peter
Published: June 2005

We report on 12 prenatal diagnoses performed between weeks 10 and 13 on normal women with a well‐documented family history of the Martin‐Bell syndrome. Seven were obligate and three were potential carriers. One male and 2 female fetuses were found to be fragile X [fra(X)]‐positive. The diagnoses were confirmed in fibroblasts or lymphocytes after interruption or postnatally. In one fra(X)‐negative female fetus, the analysis of linked DNA markers indicated that most probably she was a heterozygote. Reexamination after birth gave a fra(X)‐positive result. Hence this was a case of a false‐negative prenatal fra(X) result. The occurrence of falsenegative cytogenetic results represents a common problem that limits the sensitivity of prenatal diagnostics in the Martin‐Bell syndrome. A study of linked DNA markers can improve the reliability of negative cytogenetic results in first trimester prenatal diagnosis. In case of doubt, the chromosomes could be reexamined after fetal blood sampling.