bluuebunny/crossref_metadata_2025 huggingface dataset:
Cognitive functioning and information processing of adult mentally retarded men with fragile‐X syndrome
Authors: Maes B. , Fryns J.‐P. , Van Walleghem M. , Van den Berghe H.
Published: June 2005

The present study describes cognitive skills and information processing strategies of mentally retarded fra(X) men. Fifty‐eight fra(X) positive and 58 fra(X) negative adults, matched on sex, chronological age, length of institu‐tionalisation, general cognitive level, and living conditions, were evaluated with the Bayley or McCarthy Scales of Mental Abilities. Mental ages were mostly situated in the severe mental handicap category and were found to be negatively influenced by chronological age. A relative strength in perceptual performance and non‐verbal reasoning and a deficit in sequential information processing turned out to be typical of all mentally retarded subjects, irrespective of fra(X) or control status. Fra(X) adults could be significantly differentiated from control persons on the ground of a higher level of acquired knowledge because of better vocabulary and verbal‐expressive skills. On the other hand, they were less able to imitate non‐verbal patterns, had more difficulty with visual‐motor integration and co‐ordination, and applied less efficient general mental processing skills in solving new problems. The memory profile of fra(X) adults was strongly determined by the meaning and the complexity of the information that has to be reproduced. In this article the profile of cognitive strengths and weaknesses in the fra(X) group will be discussed and some general advice for training is suggested. © 1994 Wiley‐Liss, Inc.
Vohwinkel syndrome (mutilating keratoderma) associated with craniofacial anomalies
Authors: Sensi A. , Bettoli V. , Zampino M. R. , Gandini E. , Calzolari E.
Published: June 2005

We describe a female patient with Vohwinkel syndrome (mutilating palmoplantar keratoderma), who in addition showed cleft lip and palate, microcephaly, facial asymmetry, and other anomalies. © 1994 Wiley‐Liss, Inc.
Abnormal bile acids in the Smith‐Lemli‐Opitz syndrome
Authors: Natowicz Marvin R. , Evans James E.
Published: June 2005

The urinary bile acids from four patients with Smith‐Lemli‐Opitz (SLO) syndrome were analyzed by continuous flow fast atom bombardment mass spectrometry. Two types of abnormalities were noted: (1) a deficiency of normal bile acids (cholenoates) and (2) the presence of abnormal species postulated to be cholenoates and cholestenoates. The finding of abnormal urinary bile acids in children with SLO syndrome led to further investigation of the cholesterol metabolic pathway and to the delineation of a new inborn error of metabolism, deficient conversion of 7‐dehy‐drocholesterol to cholesterol [Irons et al., 1993]. The abnormalities of urinary bile acids, if confirmed by further structural analyses and studies of additional patients, provide an explanation for various aspects of the gastrointestinal abnormalities and growth retardation noted in SLO syndrome and suggest that exogenous bile acid replacement may play an important role in the therapy of patients with this syndrome. © 1994 Wiley‐Liss, Inc.
Spondylocarpotarsal synostosis syndrome (with or without unilateral unsegmented bar)
Authors: Langer Leonard O. , Gorlin Robert J. , Donnai Dian , Hamel Ben C. J. , Clericuzio Carol
Published: June 2005

Spondylocarpotarsal synostosis syndrome is characterized by autosomal recessive inheritance, failure of normal spinal segmentation causing symmetrical block vertebrae or scoliosis, and lordosis. There is a disproportionately short trunk. Some patients have a unilateral unsegmented bar. Other skeletal changes include carpal synostosis, usually capitate‐hamate and lunate‐triquetrum. Tarsal synostoses were present in patients in whom the feet were radiographed. Stature is short. The feet are flat. Cleft palate and sensorineural or mixed hearing loss are variable manifestations. We have reviewed the literature and present 6 new patients, 2 of them sibs. © 1994 Wiley‐Liss, Inc.
Atypical acrofacial dysostosis syndrome
Authors: Christianson Arnold L. , Kruger Hester , Dini Laurette
Published: June 2005

We describe a male fetus with a combination of defects, including severe mandibulofacial dysostosis, holoprosencephaly, upper limb deficiency, and microgastria. These abnormalities indicate a severe defect of gastrulation/blastogenesis predominantly affecting cephalad structures. This combination of anomalies has to our knowledge not previously been described.

We propose that the anomaly pattern represents either a blastogenesis‐related association, or a microgastria‐limb deficiency polytopic field defect. © 1994 Wiley‐Liss, Inc.
Deafness, sensory neuropathy, and ovarian dysgenesis: A new syndrome or a broader spectrum of Perrault syndrome?
Authors: Linssen Wim H. J. P. , Van den Bent Martin J. , Brunner Han G. , Poels Petra J. E.
Published: June 2005

We report on 3 sibs (2 males and one female) with sensorineural deafness. The presence of ovarian dysgenesis in the girl suggested a diagnosis of Perrault syndrome. In addition our patients have a sensory polyneuropathy and amelogenesis imperfecta. Two of the patients have mild mental retardation, fine choreatic movements, and dyspraxia. It is discussed whether these findings are part of a separate clinical entity or should be included within the spectrum of the Perrault syndrome. © 1994 Wiley‐Liss, Inc.
Epidemiological analysis of outcomes of pregnancy in diabetic mothers: Identification of the most characteristic and most frequent congenital anomalies
Authors: Martínez‐Frías María Luisa
Published: June 2005

Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), consisting of 19,039 consecutive malformed infants of unselected pregnancies, we have analyzed the relationship between nongestational maternal diabetes and different groups of congenital anomalies. The total sample of malformed babies was separated into two groups: children of nongestational diabetic mothers, and those of nondiabetic women. Analysis of the proportion of children identified in each group with different types of anomalies allows us to demonstrate that the most characteristic group of congenital anomalies observed in the children of diabetic women belongs to the caudal dysgenesis complex, while congenital heart defects are the most frequent malformations in these children. On the other hand, these children also present a multiple congenital anomalies (MCA) pattern more frequently than those of nondiabetic women. From this study it is also clear that the proportion of blastogenic malformations is higher in the offspring of diabetic mothers. © 1994 Wiley‐Liss, Inc.
Deletion 5q35.3
Authors: Stratton Robert F. , Tedrowe Nancy A. , Tolworthy Janet A. , Patterson Robert M. , Ryan Stephen G. , Young Robert S.
Published: June 2005

We report on a 15‐month‐old boy with a de novo deletion of the terminal band of 5q, macrocephaly, mild retrognathia, anteverted nares with low flat nasal bridge, telecanthus, minor earlobe anomalies, bell‐shaped chest, diastasis recti, short fingers, and mild developmental delay. © 1994 Wiley‐Liss, Inc.
Desbuquois syndrome complicated by obstructive sleep apnoea and cervical kyphosis
Authors: Ogle R. F. , Wilson M. J. , Kozlowski K. , Sillence D. O.
Published: June 2005

We present two children with Desbuquois syndrome and characteristic facial appearance, and musculoskeletal and radiological findings. Two new complications of this syndrome are obstructive sleep apnoea and severe cervical kyphosis. © 1994 Wiley‐Liss, Inc.
Autosomal dominant polycystic kidney disease in the fetus
Authors: Michaud Jacques , Russo Pierre , Grignon Andrée , Dallaire Louis , Bichet Daniel , Rosenblatt David , Lamothe Estelle , Lambert Marie
Published: June 2005

We report on 3 cases with a fetal presentation of autosomal dominant polycystic kidney disease (ADPKD), which illustrate the variable expression of ADPKD during fetal life. Fetus 1 was diagnosed at 20 weeks of gestation by ultrasonography; a molecular prenatal diagnosis was performed at 10 weeks on fetus 2, a sib of fetus 1; and ADPKD was an incidental finding in fetus 3 who was aborted at 16 weeks for anencephaly. All pregnancies were terminated and pathologic studies of the fetal kidneys were performed. From these cases and a review of the literature, we draw the following conclusions: (1) so far, all fetal ADPKD kidneys that have been histologically studied have shown cystic dilatations; 28/32 of these fetuses had ultrasonographic manifestations of the disease and/or had sibs with an early‐onset form of it; (2) these cysts can be found in newly formed nephrons (fetus 2), predominantly in the more mature nephrons of the deep cortex (fetus 1) or more sparsely distributed in the cortex (fetus 3); these different patterns may reflect different rates of progression of the disease; (3) in contrast to the histologic findings in adult kidneys, glomeruli seem to be predominantly affected in fetal ADPKD; (4) severe fetal expression of ADPKD seems to cluster in some families; and (5) so far, all DNA analyses performed in families with subjects presenting during the fetal or neonatal period have been consistent with linkage to the PKD1 locus. © 1994 Wiley‐Liss, Inc.
Hormonal regulation in children and adults with Williams–Beuren syndrome
Authors: Partsch C.‐J. , Pankau R. , Blum W. F. , Gosch A. , Wessel A.
Published: June 2005

Short stature is found in about 50% of children with Williams–Beuren syndrome (WBS). Disease‐specific growth curves for the syndrome showed the presence of a pubertal growth spurt in both sexes. Detailed investigations on the hormonal regulation in patients with WBS have not been performed. We studied plasma gonadotropins, sex steroids, adrenal androgens, and insulin‐like growth factors (IGF‐I and IGF‐II) and their binding protein 3 (IGFBP‐3) in a large number of WBS patients from infancy to adulthood (n = 23 females, n = 33 males). In most WBS patients, basal LH and FSH levels were within normal limits for age and pubertal stage. Nevertheless, elevated levels for basal LH and FSH were found in 35 and 44% of girls and 3 and 33% of boys, respectively. Estradiol and testosterone levels were elevated in 9.5 and 15.4% of patients, respectively. Dehydroepiandrosterone sulfate levels were elevated for age and pubertal stage in 30% of the girls and in 39% of the boys. IGF‐I was within the reference range in both sexes except for 3 patients who showed slightly decreased levels of IGF‐I. In 9 of 43 patients, IGF‐II levels were decreased below normal. In contrast, 46% of the IGFBP‐3 levels were increased above the reference range. From the 18 patients who underwent GnRH testing, five of six adults showed markedly increased basal and stimulated FSH levels and in most cases also elevated LH levels. Although all adults achieved full sexual maturation (n = 42), the high percentage of decreased testicular volumes (27%) and the results of the GnRH tests suggest a dysfunction of gonadal peptide production and spermatogenesis. The relatively high percentage of elevated gonadotropin and sex steroid levels corresponded well to the early‐normal puberty seen in female WBS patients. In view of the normal IGF‐I levels, growth hormone deficiency is not likely to be the cause of short stature in WBS but rather the aneuploidy effect in a contiguous gene syndrome. © 1994 Wiley‐Liss, Inc.
Proximal deletion of chromosome 21 confirmed by in situ hybridization and molecular studies
Authors: Courtens W. , Petersen M. B. , Noël J. C. , Flament‐Durand J. , Van Regemorter N. , Delneste D. , Cochaux P. , Verschraegen‐Spae M. R. , Van Roy N. , Speleman F. , Koenig U. , Vamos E.
Published: June 2005

Foetal blood sampling was performed at 35 weeks of gestation due to abnormal foetal ultrasound findings. There was apparent monosomy 21 (45,XX,‐21) in all mitoses analyzed. The infant died at 37 weeks during delivery. Examination disclosed facial anomalies, clubfeet, hypoplasia of the left urogenital tract, agenesis of corpus callosum, ventricular dilatation, and heterotopias. Reevaluation of the karyotype showed an unbalanced translocation t(1;21) (q44;q22.11) which resulted from a maternal balanced translocation. These findings were confirmed by fluorescence in situ hybridization and molecular studies with chromosome 21 specific markers. The latter showed a proximal deletion of the maternally derived chromosome 21 including all loci from centromere down to the D21S210 locus. This case illustrates the need for complementary cytogenetic and molecular investigations in cases of apparent monosomy 21. © 1994 Wiley‐Liss, Inc.
Fragile X phenotype in a patient with a large de novo deletion in Xq27‐q28
Authors: Albright Susan G. , Lachiewicz Ave M. , Tarleton Jack C. , Rao Kathleen W. , Schwartz Charles E. , Richie Renee , Tennison Michael B. , Aylsworth Arthur S.
Published: June 2005

A 2‐year‐old boy with manifestations of the fragile X syndrome was found to have a cytogenetically visible deletion of Xq27‐q28 including deletion of FMR‐1. Molecular analysis of the patient was recently described in Tarleton et al. [1993: Hum Mol Genet 2(11): 1973–1974] and the deletion was estimated to be at least 3 megabases (Mb). His mother had 2 FMR‐1 alleles with normal numbers of CGG repeats, 20 and 32, respectively. Thus, the deletion occurred as a de novo event. The patient does not appear to have clinical or laboratory findings other than those typically associated with fragile X syndrome, suggesting that the deletion does not remove other contiguous genes. This report describes the phenotype of the patient, including psychological studies. © 1994 Wiley‐Liss, Inc.
Reliability of diagnostic assessment of normal and premutation status in the fragile X syndrome using DNA testing
Authors: Fisch Gene S. , Nelson David L. , Snow Karen , Thibodeau Stephen N. , Chalifoux Maryse , Holden Jeanette J. A.
Published: June 2005

Until recently, fragile X [fra(X)] syndrome was diagnosed by cytogenetic techniques and/or linkage analysis. Investigation of the mutation at the molecular level has shown that amplification of a polymorphic trinucleotide repeat (CGG) is diagnostic of this syndrome. Fu et al. [1991] observed that between 6–54 copies of the repeat were associated with alleles found in the general population, whereas 50–200 copies were associated with the premutation. In general, differences in copy number between the normal and premutated states are sufficiently large so that the probability of misclassification is, for all practical purposes. zero. However, there is a grey area in which members from both populations overlap. The purpose of our study was to determine the probability of misclassifying an individual from either the general or premutation population. DNA obtained from the general population and transmitting fra(X) females were analyzed from 3 centers in North America: Houston, Texas; Rochester, Minnesota; and Kingston, Ontario. The distribution of normal alleles from Houston was not significantly different from those obtained from Rochester. Therefore, these 2 samples were combined and the pooled distribution of normal alleles was compared with the pooled distribution of premutations. Results indicated that if 50 repeats were used as the cutoff criterion, sensitivity is 100%, specificity is 99.6%, and the probability that an individual has the fra(X) premutation given that the number of repeats is greater than 50 is 95%. Other cutoff criteria (45, 55, 60, 65) employed produced like findings, although 55 repeats appears to be a marginally superior criterion to 50. An independent sample from Kingston was used to verify the original assessments. Results indicated no significant differences when the pooled Houston/Rochester distribution was compared with the distribution of repeats found in the general population from Kingston. Our findings indicate that family studies should be done to establish stability/instability of alleles when more than 55 repeats are found in the proband. © 1994 Wiley‐Liss, Inc.
Behavior problems of young girls with fragile X syndrome: Factor scores on the Conners' parent's questionnaire
Authors: Lachiewicz Ave M. , Dawson Deborah V.
Published: June 2005

Mothers of 60 girls with fragile X [fra(X)] and 58 controls were asked to fill out the Conners' Parent's Questionnaire to determine if this commonly used checklist would detect behavior problems in young girls with fra(X). The mean T‐scores were significantly different between the 2 groups of girls on 5 of the 6 factors on the Conners' Parent's Questionnaire and the girls with fra(X) had mean T‐scores that were above the average range on both the Anxiety factor and the Hyperactivity Index factor. Significantly more girls had T‐scores greater than 70 (>98th centile) on 3 of the 6 factors. Twenty‐three percent of the girls had T‐scores greater than 70 on the Anxiety factor and 38% of the girls had T‐scores greater than 70 on the Hyperactivity Index factor. This study suggests that some behavior problems will be reported frequently in young girls with fra(X) and should not be difficult for clinicians to detect. © 1994 Wiley‐Liss, Inc.
Apparently enhanced visual information processing in female fragile X carriers: Preliminary findings
Authors: Steyaert J. , Borghgraef M. , Fryns J. P.
Published: June 2005

Eighteen normally intelligent adult female fragile X carriers were tested with the “de Sonneville Visual Attention Tasks,” a computer‐based set of reaction‐time experiments, in order to assess different aspects of their attention capacity. The subject group was compared with a group of 48 adults, who were not known to be fragile X carriers. We publish preliminary results of this study. These show that the fragile X carriers have significantly faster reaction times at a substantial number of the tests. This suggests that normally intelligent female fragile X carriers might process simple visual information, such as the targets offered in these reaction time experiments, at a faster rate than control women. © 1994 Wiley‐Liss, Inc.
Fragile X founder chromosome effects: Linkage disequilibrium or microsatellite heterogeneity?
Authors: Zhong Nan , Ye Lingling , Dobkin Carl , Brown W. Ted
Published: June 2005

Previous studies of founder chromosome effects in fragile X have been based on linkage disequilibrium with either FRAXAC1 or DXS548 alone or combined with FRAXAC2. Recently, we found no linkage disequilibrium of FMR‐1 with FRAXAC2, but rather, found FRAXAC2 was complex and highly mutable. Therefore, we have now analyzed FRAXAC1 and DXS548 together for haplotypes, two markers which have not been jointly analyzed previously, to test for disequilibrium. We typed 315 fragile X (FX) chromosomes and controls, further subdivided into large controls (LC) and small controls (SC) with ≤35 repeats and identified 26 different haplotypes. Two were more frequent and one less frequent in FX than SCs, thus confirming apparent linkage disequilibrium in fragile X. However, we noted increased FX microsatellite heterozygosity, either individually (results quite similar to previous studies) or as haplotypes. This heterozygosity covaried with FX > LC > SC, which may indicate alternative explanation exists for the apparent disequilibrium. We hypothesize that large FMR‐1 CGG repeat allele genes may be associated with the generation of new microsatellite mutations. Possible mechanisms include gene conversions between CGG repeats and flanking microsatellites involving unequal double cross‐overs, the expansion of small control CGGs to larger sizes associated with episodic generalized microsatellite instability or as a direct result of mutant FMR‐1 gene function. We conclude that the founder effects observed with the use of these CA repeats is likely to reflect both linkage disequilibrium and increased microsatellite instability of fragile X chromosomes. © 1994 Wiley‐Liss, Inc.
Prevalence of fra(X) in the county of Funen in Denmark is lower than expected
Authors: Tranebjaerg L. , Hilling S. , Jessen J. , Lind D. , Hansen M. S.
Published: June 2005

Population based cytogenetic fra(X) surveys have not previously been reported from Denmark. In the present study we present an estimate of fra(X) based on 1) information from the Danish Central Cytogenetic Registry of diagnosed fra(X) males of all age groups in all Denmark in the period 1980–1992 and 2) a systematic cytogenetic fra(X) survey of 175 of 8–10‐year‐old children with special educational needs resident in a defined, demographically representative area of Denmark (the county of Funen). The study was performed in 1988‐90 before the cloning of the FMR‐1 gene. In the county of Funen there were 7,837 male children in the age group of 8‐10 years. In the cytogenetic survey of learning disabled children, no fra(X) positive was diagnosed.

There were 99 registered males with fra(X) in all Denmark, equivalent to a prevalence of 0.04 per 1,000 males (confidence interval 0.032:1,000–0.048:1,000).

Molecular fra(X) surveys of different, large populations are needed in order to estimate the frequency of fra(X) and clarify whether significant differences in prevalence exist in different populations. © 1994 Wiley‐Liss, Inc.
Butyrate and acetyl‐carnitine inhibit the cytogenetic expression of the fragile X in vitro
Authors: Pomponi Maria Grazia , Neri Giovanni
Published: June 2005

Cytogenetic expression of the fragile site at Xq27.3 is only found in those patients who have a full mutation of the FMR1 gene, i.e., a large amplification of the CGG repeat. However, an expansion of this repeat, although necessary, does not seem to be sufficient to cause expression of fra (X)(q27.3). Other factors are clearly needed, e.g., thymidylate stress. Little or no attention has been paid to the possible role of histones in the expression of the fragile sites, in spite of their structural and regulatory role in the chromatin complex. Histones can be modified by treating intact cells in vitro with butyrate, a substance that causes histone acetylation. The purpose of the present work is to test the effect of butyrate and of the acetylating compound acetyl‐L‐carnitine on the expression of fra (X)(q27.3) by treating peripheral lymphocytes of fragile X syndrome patients with these substances in vitro. we show that this treatment causes a significant inhibition of fra (X)(q27.3) expression. © 1994 Wiley‐Liss, Inc.
Comparison between the cytogenetic test for fragile X and the molecular analysis of the FMR‐1 gene in Japanese mentally retarded individuals
Authors: Hofstee Yvonne , Arinami Tadao , Hamaguchi Hideo
Published: June 2005

The prevalence of the fragile X syndrome has been estimated by the results of population studies in which the disease was mostly diagnosed by cytogenetic examinations. To examine the reliability of the cytogenetic analysis for the estimation of the prevalence of the fragile X syndrome, the CGG repeat in the FMR‐1 gene was assayed by Southern blot hybridization and polymerase chain reaction (PCR) in an institutionalized group of mentally retarded individuals consisting of 305 males and 129 females. The data thus obtained were compared with the cytogenetic data. The DNA analysis detected 7 full mutations among the alleles of the 296 unrelated males and 2 full mutations among the alleles of the 129 unrelated females. These findings were consistent with the cytogenetic data. No premutation was found in 554 X chromosomes in the unrelated mentally retarded patients nor 826 X chromosomes in unrelated control individuals. The distribution of the CGG repeat number in the normal range was not significantly different between the mentally retarded individuals and the control individuals. These data suggest that the estimates of the prevalence of the fragile X syndrome based on cytogenetic data in the population studies are almost reliable. Based on the finding that no premutations were found in this study, a small difference in the prevalence of the fragile X syndrome between Caucasians and Japanese is suggested. © 1994 Wiley‐Liss, Inc.
Fraxa locus in fragile X diagnosis: Family studies, prenatal diagnosis, and diagnosis of sporadic cases of mental retardation
Authors: von Koskull Harriet , Gahmberg Nina , Salonen Riitta , Salo Armi , Peippo Maarit
Published: June 2005

Three hundred eighty‐seven individuals from 32 Finnish fragile X families were studied, using the probe StB12.3 [Oberlé et al., 1991: Science 252:1097–1102] for the FRAXA locus, to reveal length variations in the FMR‐1 gene. As expected, the affected individuals (with few exceptions) showed a full mutation; a few affected individuals with a premutation only were found. Seventy percent of the females with a full mutation were affected. The size of the mutation remained unchanged in 6, increased in 73, and decreased in 6 female meioses. In male meioses the size was unchanged in 15 cases, increased in 2 cases, and decreased in 1 case. Prenatal diagnosis was performed in 20 cases. In 7 of these the mutation was inherited by the fetus. Four hundred sixty‐four mentally retarded patients were referred to us for FRAXA analysis. In 5% of these the fragile X mutation was found. In addition to the clear cut negative or positive results there were 6 cases in which an increase of 50–80 bp was detected. These findings may represent either large normal alleles or small premutations suggesting a possible tissue mosaicism which could explain the retardation of the patients. © 1994 Wiley‐Liss, Inc.
Prenatal diagnosis in known fragile X carriers
Authors: Maddalena Anne , Hicks Belynda D. , Spence W. Christine , Levinson Gene , Howard‐Peebles Patricia N.
Published: June 2005

Prenatal diagnosis for fragile X syndrome was performed in 34 pregnancies of 33 known carriers, on 22 chorionic villus samples (CVS), and 15 amniocentesis samples. Fetal and maternal DNA were analyzed by the EagI/EcoRI Southern blot of Rousseau et al. [1991: N Engl J Med 325:1673–1681], with detection of full mutations ensured by a second loading with brief electrophoresis. As a supplemental assay for full mutations, cytogenetic induction was performed in 20 cases. Positive cytogenetic results were helpful in confirming full mutations in CVS cases where the fetal DNA was intermediate in appearance, between a large premutation and a small full mutation. Of 8 mothers with full mutations, the fetal results were 5 full, 2 normal, and 1 premutation (whose mother was a full/pre compound heterozygote). Of 26 mothers with premutations, the fetal results were 5 full, 13 normal, 7 premutation, and 1 uninterpretable (maternal contamination). Maternal premutations were sized in kb by Southern blot and in CGG repeat number by PCR; the predicted correlation between maternal length and penetrance was seen. Follow‐up studies include 3 full mutations and 2 premutations confirmed by DNA analysis at birth. Maternal contamination of CVS samples was encountered in 3 of 22 cases, illustrating the value of EagI in detecting maternal (lyonized) chromosomes. © 1994 Wiley‐Liss, Inc.
Mosaicism in fragile X affected males
Authors: Nolin Sarah L. , Glicksman Anne , Houck George E. , Brown W. Ted , Dobkin Carl S.
Published: June 2005

Fragile X affected males have an expansion of a CGG repeat and a hypermethylated CpG island 5′ to the FMR‐1 gene. Mosaic males with both a premutation and full mutation have been noted among the affected individuals. Such mosaic males are most easily identified by the presence of a methylated restriction fragment characteristic of the full mutation and an additional unmethylated fragment in the premutation range in Southern analyses with EcoR I and the methylation‐sensitive enzyme Eag I and a probe such as StB12.3. We analyzed a group of affected fragile X males by Southern blotting and found 41% (61/148) to be mosaic. The 148 individuals were divided between 36 pairs of brothers and 76 unrelated males. Little difference in the number of mosaics was seen between the brothers and the unrelated males nor was the expected distribution of mosaicism in brother pairs different from observed. Thus, these data do not suggest a familial basis for mosaicism. Our observation that 41% affected fragile X males were mosaic is significantly higher than previous reports. The difference is likely due to technical modifications which permitted the identification of faint premutation bands in some patients. The high percentage of affected males with mosaicism seen here suggests that the occurrence of such individuals may be a much more frequent event than presently recognized. © 1994 Wiley‐Liss, Inc.
Conservation of CGG region in FMR1 gene in mammals
Authors: Deelen Wout , Bakker Cathy , Halley Dicky J. J. , Oostra Ben A.
Published: June 2005

Only two of the fragile sites found in humans (FRAXA and FRAXE) have been associated with a clinical phenotype. In mentally retarded individuals with cytogenetic expression of FRAXA a CGG repeat in the FMR1 gene is amplified. Fragile sites are found in many animal species. We have analyzed the FRAXA region containing the CGG repeat in several different species by PCR amplification. In most mammals this region could be amplified; the number of copies of the repeat is deduced. © 1994 Wiley‐Liss, Inc.
Towards identification of X‐linked mental retardation genes: A proposal
Authors: Mandel J. L.
Published: June 2005

Identification of X linked mental retardation (XLMR) genes that can only be broadly localised by linkage analysis will ultimately depend on systematic screening of many probands for mutations in many candidate genes. This would be more efficiently performed by analysis of mRNA (or illegitimate transcripts) by reverse transcriptase‐polymerase chain reaction (RT‐PCR). A scheme is proposed that associates standardized reporting of XLMR families, including small families that would not by themselves yield statistically significant linkage information, and deposit of a lymphoblastoid cell line for one proband of each family to an accessible repository. © 1994 Wiley‐Liss, Inc.
Arylsulfatase a psedodeficiency: A common polymorphism which is associated with a unique haplotype
Authors: Zlotogora Joël , Furman‐Shaharabani Yael , Goldenfum Sandra , Winchester Bryan , Figura Kurt Von , Gieselmann Volkmar
Published: June 2005

The allele for pseudodeficiency (PD) of the lysosomal enzyme arylsulfatase A (ARSA) is a common polymorphism in all populations. The PD allele frequency in different Israeli ethnic groups was found to range from 9.2–22.7%. The PD allele includes two different mutations PD (1) and PD (2) in an aproximatively 1 Kb interval. In this study we confirmed that while PD (1) may be found alone as a polymorphism, PD (2) is always associated with the PD allele (660 alleles screened). Analysis of three ARSA intragenic polymorphisms showed a complete linkage disequilibrium between the PD allele and an haplotype defined by the three polymorphic restriction sites. The results suggest that the origin of the PD polymorphism may be a common founder, or recurrent mutations which are occurring in a unique haplotype. © 1994 Wiley‐Liss, Inc.
Molecular and clinical study of 61 Angelman syndrome patients
Authors: Saitoh Shinji , Harada Naoki , Jinno Yoshihiro , Hashimoto Katsuyo , Imaizumi Kiyoshi , Kuroki Yoshikazu , Fukushima Yohimitsu , Sugimoto Tateo , Renedo Mónica , Wagstaff Joseph , Lalande Marc , Mutirangura Apiwat , Kuwano Akira , Ledbetter David H. , Niikawa Norio
Published: June 2005

We analyzed 61 Angelman syndrome (AS) patients by cytogenetic and molecular techniques. On the basis of molecular findings, the patients were classified into the following 4 groups: familial cases without deletion, familial cases with submicroscopic deletion, sporadic cases with deletion, and sporadic cases without deletion. Among 53 sporadic cases, 37 (70%) had molecular deletion which commonly extended from D15S9 to D15S12, although not all deletions were identical. Of 8 familial cases, 3 sibs from one family had a molecular deletion involving only 2 loci, D15S10 and GABRB3, which define the critical region for AS phenotypes. The parental origin of deletion, both in sporadic and familial cases, was exclusively maternal and consistent with a genomic imprinting hypothesis. Among sporadic and familial cases without deletion, no uniparental disomy was found and most of them were shown to inherit chromosomes 15 from both parents (biparental inheritance). A discrepancy between cytogenetic and molecular deletion was observed in 14 (26%) of 53 patients in whom cytogenetic analysis could be performed. Ten (43%) of 23 patients with a normal karyotype showed a molecular deletion, and 4 (13%) of 30 patients with cytogenetic deletion, del(15) (q11q13), showed no molecular deletion. Most clinical manifestations, including neurological signs and facial characteristics, were not distinct in each group except for hypopigmentation of skin or hair. Familial cases with submicroscopic deletion were not associated with hypopigmentation. These findings suggested that a gene for hypopigmentation is located is located outside the critical region of AS and is not imprinted. © 1994 Wiley‐Liss, Inc.
Knobloch syndrome in a large Brazilian consanguineous family: Confirmation of autosomal recessive inheritance
Authors: Passos‐Bueno M. Rita , Marie Suely K. , Monteiro Mario , Neustein Isaac , Whittle Martin R. , Vainzof Mariz , Zatz Mayana
Published: June 2005

Knobloch syndrome is a rare genetic disorder characterized by high myopia, vitreoretinal degeneration with retinal detachment and occipital cephalocele. The inheritance has been described as autosomal recessive (AR) but in addition to the original report with 5 affected patients [Knobloch and Layer, 1971] only one other family with 2 affected sibs has been described [Czeizel et al., 1992]. We have studied a large consanguineous kindred in which there are 12 patients with severe ocular alterations associated with a congenital occipital encephalocele, compatible with the diagnosis of Knobloch syndrome. CT scan and MRI performed in one of the patients, allowed a better understanding of the cranial and ocular alterations in this syndrome. The pattern of occurrence in this highly inbred family clearly confirms autosomal recessive inheritance of Knobloch syndrome. © 1994 Wiley‐Liss, Inc.
Apparent genetic homogeneity of the treacher Collins‐Franceschetti syndrome
Authors: Edery Patrick , Manach Yves , Le Merrer Martine , Till Marianne , Vignal Alain , Lyonnet Stanislas , Munnich Arnold
Published: June 2005

The Treacher Collins‐Franceschetti syndrome (TCOF) or mandibulofacial dysostosis (MFD) is an autosomal dominant disorder characterized by craniofacial abnormalities and hearing loss. A refined genetic linkage map of the TCOF locus was established in 8 independent families, using 12 microsatellite DNA markers of the distal 5q. Positive lod score values were obtained for all markers with a maximum at the D5S413 locus (Zmax = 3.79 at θ = 0%). Multipoint linkage analysis and haplotype analysis supported the location of the gene between loci D5S434 and D5S412. These results are consistent with previous linkage analysis [Dixon et al.: Am J Hum Genet 49:17–22, 1991, Am J Hum Genet 52:907–914, 1993; Jabs et al.: Genomics 11:193–198, 1991, Genomics 18:7–13, 1993] and provide further evidence of genetic homogeneity in this syndrome. © 1994 Wiley‐Liss, Inc.
Additional case of female monozygotic twins discordant for the clinical manifestations of Duchenne muscular dystrophy due to opposite X‐chromosome inactivation
Authors: Abbadi N. , Philippe C. , Chery M. , Gilgenkrantz H. , Tome F. , Collin H. , Theau D. , Recan D. , Broux O. , Fardeau M. , Kaplan J.‐C. , Gilgenkrantz S.
Published: June 2005

A pair of female monozygotic (MZ) twins, heterozygous carriers for a deletion in the DMD gene and discordant for the clinical manifestations of Duchenne muscular dystrophy, were analyzed by molecular studies, in situ hybridization, and methylation pattern of X chromosomes to search for opposite X inactivation as an explanation of their clinical discordance. Results in lymphocytes and skin fibroblast cell lines suggest a partial mirror inactivation with the normal X chromosome preferentially active in the unaffected twin, and the maternal deleted X chromosome preferentially active in the affected twin. A review shows that MZ female twins discordant for X‐linked diseases are not uncommon. Twinning and X inactivation may be interrelated and could explain the female twins discordant for X‐linked traits. © 1994 Wiley‐Liss, Inc.
Discordant infantile encephalopathy with symmetrical thalamic calcifications in identical twins
Authors: van der Knaap M. S. , Barth P. G.
Published: June 2005

Connatal thalamic calcifications in apparently uneventful pregnancies have been described in various case reports and in a single report in two sibs. On the other hand, this lesion is known to occur after a hypoxicischemic accident in the immature brain. In the present report infantile encephalopathy with symmetrical thalamic calcifications is observed in one sib of a monozygous twin pair. This observation adds to the evidence that the condition is acquired, most probably on the basis of hypoxia‐ischemia, and provides strong evidence against autosomal‐recessive inheritance. © 1994 Wiley‐Liss, Inc.
Linguistic abilities in children with Williams‐Beuren syndrome
Authors: Gosch Angela , Städing Gabriele , Pankau Rainer
Published: June 2005

In recent studies children with Williams‐Beuren syndrome (WBS) have been characterized as having a distinct neuropsychological profile with verbal abilities being superior to visuo‐spatial and motor skills. An unusual command of language, including excessive use of verbal stereotypes, social phrases, and clichés has been noticed.

The aim of this study is to establish whether the quality and quantity of verbal behavior, and the articulation and tonal quality of the voices of children with WBS differ from other children with nonspecific developmental disabilities.

A group of 25 children with WBS and a control group of 25 children matched for age (4–10 years), sex (12 girls; 13 boys), and nonverbal reasoning abilities (mean IQ = 79) were investigated. The Heidelberg Language Development Test and a picture story were administered. The mothers were asked to answer a questionnaire to assess the articulation and the vocal characteristics of their children.

The results show that children with WB syndrome do not differ in most qualitative and quantitative tasks with regard to verbal competence. They produce significantly more correct plural‐singular formations than the control children (t = 2.49, P < 0.01) on a primitive level of grammatical competence.

In general, their articulation was reported to be more exact and clear (t = −2.73, P < 0.006). More mothers of children with WBS noticed a production of stereotypes, the use of social phrases, and clichés than did mothers of the control children (Chi square = −6.67 P < 0.005). Children with WBS were less likely to lisp as compared to the control children (Chi square = 2.08, P = 0.074).

Finally, the voices of the children with WBS were judged to be deeper, hoarse, and “rough” than the voices of the control children. © 1994 Wiley‐Liss, Inc.
Syndrome of hypoparathyroidism, growth hormone deficiency, and multiple minor anomalies
Authors: Marsden Deborah , Nyhan William L. , Sakati Nadia O.
Published: June 2005

A 5 1/2‐year‐old Saudi Arabian girl presented with a syndrome of intrauterine growth retardation, minor anomalies, hypoparathyroidism, and growth hormone deficiency. She was the product of a consanguineous mating. Her minor anomalies and delayed development were similar to findings in a previously reported Saudi Arabian patients with hypoparathyroidism and growth deficiency. There were substantial differences in findings from a series of Kuwaiti children. Parathyroid hormone was undetectable, but the renal response to infused parathyroid hormone was normal, indicating primary hypoparathyroidism. In response to arginine stimulation, her GH rose to 5.8 ng/ml (5.8 μg/L) (nl > 10), and to 2.3 ng/ml (2.3 μg/L) after L‐dopa. Following clonidine it rose to 15 ng/ml (15 μg/L) at 120 minutes. She responded normally to infusions of GHRH (GH rose to 22 ng/ml (22 μg/L) at 75 minutes) and TRH (TSH rose to 37 μu/ml, 37 mlU/L). On treatment with recombinant human growth hormone, she showed an increase in height and weight. Hypocalcemia was well controlled with supplemental 1‐α‐cholecalciferol. © 1994 Wiley‐Liss, Inc.
Direct and inverted reciprocal chromosome insertions between chromosomes 7 and 14 in a woman with recurrent miscarriages
Authors: Wang Ying‐Tai , Bajalica Svetlana , Han Fei‐Yu , Wang Zhao‐Cai , Bui The‐Hung , Xie Ya‐Gang
Published: June 2005

We present the first case of direct and inverted reciprocal chromosome insertions between human chromosomes 7 and 14, ascertained because of repeated spontaneous abortions. Prometaphase GTG banding analysis showed the karyotype to be 46, XX, inv ins (7;14)(7pter→7q11.23::14q32.2→14q22::7q21.2→7qter), dir ins(14;7)(14pter→14q22::7q11.23→7q21.2::14q32.2→14qter). Origins of the insertion have been confirmed by chromosome painting with libraries specific for chromosomes 7 and 14 using fluorescence in situ hybridization. © 1994 Wiley‐Liss, Inc.
Genetics of the Costello syndrome
Authors: Lurie Iosif W.
Published: June 2005

Although Costello syndrome is considered to be an autosomal recessive disorder, review of 20 families demonstrated that the 37 sibs of the probands were all normal. In 6 families on whom pedigrees were not available, 2 affected sib‐pairs were born. Even if there were no normal offspring in these latter families, the occurrence of the Costello syndrome in only 2 of 39 sibs virtually excludes an autosomal recessive inheritance pattern (P = 0.999). Moreover, a significant increase of mean paternal age (38.0 yr) and paternal‐maternal age difference (7.36 yr) suggests sporadic autosomal dominant mutations as a likely cause. The 2 reported cases of affected sibs born to healthy parents may be explained by gonadal mosaicism, although heterogeneity with a small proportion of recessively inherited cases cannot be excluded. © 1994 Wiley‐Liss, Inc.
Ancient, highly polymorphic human major histocompatibility complex DQA1 intron sequences
Authors: McGinnis Malcolm D. , Lebo Roger V. , Quinn David L. , Simons Malcolm J.
Published: June 2005

A 438 basepair intron 1 sequence adjacent to exon 2 in the human major histocompatibility complex DQA1 gene defined 16 allelic variants in 69 individuals from wide ethnic backgrounds. In contrast, the most variable coding region spanned by the 247 basepair exon 2 defined 11 allelic variants. Our phylogenetic human intron 1 tree derived by the Bootstrap algorithm reflects the same relative allelic relationships as the reported DQA1 exon 2 tree [Gyllensten and Erlich, Hum Immunol 36:1–10, 1989]. Thus 3′ DQA1 intron 1 and exon 2 have cosegregated since divergence of the human races. Comparison of human alleles to a Rhesus monkey DQA1 first intron sequence found only 10 nucleotide substitutions unique to Rhesus, with the other 428 positions (98%) found in at least one human allele. This high degree of homology reflects the evolutionary stability of intron sequences since these two species diverged over 20 million years ago. Because more intron 1 alleles exist than exon 2 alleles, these polymorphic introns can be used to improve tissue typing for transplantation, paternity testing, and forensics and to derive more complete phylogenetic trees. These results suggest that introns represent a previously underutilized polymorphic resource. © 1994 Wiley‐Liss, Inc.
Retinitis pigmentosa and related disorders: Phenotypes of rhodopsin and peripherin/RDS mutations
Authors: Shastry Barkur S.
Published: June 2005

Retinitis pigmentosa comprises a group of clinically variable and genetically heterogeneous inherited disorders of the retina. It is estimated that approximately 1.5 million people throughout the world are affected by this disease. It is a slowly progressive disorder and causes loss of night vision and peripheral visual field in adolescence. It can be inherited through an autosomal dominant, recessive, or X‐linked mode; the autosomal dominant form is considered to be the mildest form. Molecular genetic studies on the autosomal dominant disorder have shown that, in some families, genes encoding the rhodopsin and peripherin/RDS map very close to the disease loci identified previously by the systematic linkage analyses. These results, together with the observation that a recessive nonsense mutation in the Drosophila opsin gene causes photoreceptor degeneration, prompted an extensive search for the alterations in the human rhodopsin and peripherin/RDS genes in families with autosomal dominant retinitis pigmentosa. As a result, several distinct rhodopsin and peripherin/RDS mutations have been found in approximately 30% of all autosomal dominant cases. A wide variety of clinical expression of the disorder even within a family with the same mutation, its late onset, slow progression, and cone degeneration clearly suggest that some other factors or genes in addition to rhodopsin are responsible for the phenotypic expression of the disorder. In this article, an attempt is made to highlight some of these recent developments and to correlate the various mutations and the phenotypes. © 1994 Wiley‐Liss, Inc.
Autosomal dominant Muckle‐Wells syndrome associated with cystinuria, ichthyosis, and aphthosis in a four‐generation family
Authors: Berthelot J.‐M. , Maugars Y. , Robillard N. , Pascal O. , Stalder J.‐F. , David A. , Prost A.
Published: June 2005

Muckle‐Wells syndrome is a rare autosomal dominant disorder characterized by chronic recurrent urticaria, periodic arthritis, sensorineural deafness, general signs of inflammation, and secondary amyloidosis (AA type). We report on a 4‐generation family with 7 persons sharing various signs of this syndrome associated with bipolar aphthosis in 5 cases and cystinuria in one. Two other relatives in the family had ichthyosis. © 1994 Wiley‐Liss, Inc.
Clinical and molecular studies in a large Dutch family with Noonan syndrome
Authors: Van Der Burgt Ineke , Berends Ed , Lommen Ed , Van Beersum Sylvia , Hamel Ben , Mariman Edwin
Published: June 2005

We describe the largest Noonan syndrome (NS) family reported to date. The manifestations of the affected relatives are discussed. In the absence of a biochemical marker NS is still a clinical diagnosis. The diagnostic criteria that were used are presented compared with other published criteria for diagnosing NS.

The large size of this family enabled us to test the possible involvement of candidate regions by multipoint linkage analysis. Both the region surrounding the NF1 locus on chromosome 17 and the proximal part of chromosome 22 could be excluded. Since NS may well be heterogeneous, the use of such a large family in linkage studies of NS should prove indispensable. © 1994 Wiley‐Liss, Inc.
Sanfilippo syndrome type A in two adult sibs
Authors: Lindor Noralane M. , Hoffman Alan , O'Brien John F. , Hanson Norman P. , Thompson Jerry N.
Published: June 2005

We report on 2 adult sibs with Sanfilippo syndrome type A (MPS IIIA; deficiency of heparin sulfamidase) who were less functionally impaired than other reported individuals with this disorder. These individuals expand our understanding of the range of clinical expression that one may see in Sanfilippo syndrome type A. © 1994 Wiley‐Liss, Inc.