bluuebunny/crossref_metadata_2025_split huggingface dataset:
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

AbstractDiagnosis 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

AbstractA 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

AbstractMost 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

AbstractWe 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

AbstractA 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

AbstractVariability 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

AbstractOver 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

AbstractFragile 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

AbstractLymphoblastoid 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

AbstractThe 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

AbstractWe 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

AbstractWe 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.
The fra(X) syndrome: Neurological, electrophysiological, and neuropathological abnormalities
Authors: Wisniewski K. E. , Segan S. M. , Miezejeski C. M. , Sersen E. A. , Rudelli R. D. 
Published: June 2005

AbstractWe have evaluated 62 fragile X syndrome [fra(X)] individuals (55 males and 7 females) with different degrees of developmental disabilities that were clinically non‐progressive and non‐focal in character. The mean age for the 55 males was 23.1 years ± 14.3 SD with a range of 2–70: for the 7 females, the mean age was 15.7 years ± 3.5 SD with a range of 10–20 years. Mental retardation (MR) was found in 53 males (8/53 [15.1%] mild, 26/53 [49.1%] moderate, 14/53 [26.4%] severe, and 5/53 [9.4%] profound). Learning disabilities were found in 2/55 (3.6%) of males. One of the 7 females had mild and one had moderate MR: the other 5 were learning disabled. Autistic stigmata were present in 10/62 (16%) of the patients. Only 14/62 (23%) had a history of seizures, all of which were controlled with anticonvulsants. In 36/62 cases, an electroencephalogram (EEG) was performed. We compared these data with that of others. Brain stem auditory evoked response (BAER) was performed in 12 cases. Abnormalities were found in only 5/12. Neuroimaging and computerized cranial transaxial tomography (CT scan) were performed on 21/62 (34%) of the patients. Only 8 of these 21 (38%) studies were abnormal. One patient died; neuropathological studies showed mild brain atrophy, with light microscopic and ultrastructural abnormalities. Rapid Golgi dendritic spine patterns showed that the proximal apical segments were abnormally developed. Very thin, long tortuous spines with prominent terminal heads and irregular dilatations were present. Marked reductions in the length of the synapses, as determined on EPTA‐postfixed tissue where noted. The mean synaptic contact area was 35% shorter than the normal length observed in controls. In summary, the neurological abnormalities are mainly in the cognitive function, seizures appear similar to the benign age‐related epilepsies, whereas the neuropathological abnormalities are in the wiring system, showing synaptic dysgenesis.
Relationship between age and IQ among fragile X males: A multicenter study
Authors: Fisch Gene S. , Arinami Tadao , Froster‐Iskenius Ursula , Fryns Jean‐Pierre , Curfs L. M. , Borghgraef M. , Howard‐Peebles Patricia N. , Schwartz Charles E. , Simensen Richard J. , Shapiro Lawrence R. 
Published: June 2005

AbstractLongitudinal decline in IQ among fragile X males was reported recently. However, there are problems in retesting IQ that may affect scores. Two such factors are intertest time interval and score obtained on the first test. To determine the generality of IQ score changes, we examined 101 fragile X males from 6 centers. To ensure high test‐retest reliability, only results from Stanford‐Binet and Wechsler tests were used. Thus there were retest scores from 60 subjects. Test‐retest reliability between first and last scores was very good (r = 0.85) and comparable to those seen in nonfragile X mentally retarded individuals. Also computed were z‐scores of differences in IQ scores. The z‐score differences were distributed about a mean at 1 SD below the expected zero value. Eighteen subjects showed statistically significant decreases in IQ, 6 showed statistically significant increases, while 5 showed the same scores. Z‐score differences were not correlated with type of residence or elapsed intertest interval, but were negatively correlated with first score obtained, indicating a regression‐to‐the‐mean effect. Using a multiple regression analysis, we found first score obtained, age tested, and age retested significant predictors of score differences, accounting for 19% of the total variance. These results suggest that factors previously identified as affecting retest scores have a smaller effect than originally thought. It is suspected that decline in IQ is associated with dynamic neurological processes and needs to be investigated further.
Short‐term memory and cognitive variability in adult fragile X females
Authors: de von Flindt Robert , Bybel Bohdan , Chudley Albert E. , Lopes Fatima 
Published: June 2005

AbstractWe investigated the possibility that adult fragile X [fra(X)] heterozygotes have a distinct or specific cognitive profile, with a particular focus on visuospatial and/or memory deficits. With a sample of 13 adult fra(X) female carriers (2 fra(X) positive) and age‐matched control women, we performed 2 tests: Wechsler Adult Intelligence Scale‐Revised (WAIS‐R) and the Revised Visual Retention Test (RVRT). An identifiable cognitive profile was not evident in the study group, but significant differences were evident in RVRT performance in number correct and number of errors when compared to controls and normative data. The combination of the WAIS‐R and RVRT data suggests that the short‐term memory component of the tasks may be of more significance than visuospatial performance in the deficits observed.
Cognitive profiles associated with the fra(X) syndrome in males and females
Authors: Freund Lisa S. , Reiss Allan L. 
Published: June 2005

AbstractTwenty‐three fragile X [fra(X)] males (mean IQ 50, mean age 10 years) and 11 fra(X) females (mean IQ 84, mean age 11.3 years) were administered the Stanford‐Binet Intelligence Scale, 4th ed. (S‐B). The cognitive profiles generated from the S‐B indicated a pattern of subtest strengths and weaknesses that was similar for both groups. Consistent weaknesses in both groups were found in quantitative skills and short‐term memory recall for visually presented, abstract stimuli, whereas a consistent strength was observed for short‐term memory recall of visually presented, meaningful stimuli. Strengths in verbal labeling and comprehension and deficits in spatial visualization and visual‐motor coordination were identified by the S‐B for the male group but not for the female group. Fragility in the female group was negatively correlated with the S‐B score for the short‐term memory area and the combined S‐B scores for the verbal reasoning and quantitative reasoning areas. The specific, S‐B‐identified cognitive strengths and weaknesses associated with the fra(X) condition are potentially useful indicators for investigation of specific cognitive process deficits associated with the fra(X) condition and the design of appropriate educational interventions for fra(X) children.
A distinct type of hidrotic ectodermal dysplasia
Authors: Halal Fahed , Setton Nora , Wang Nai‐San 
Published: June 2005

AbstractFour individuals from 2 generations of a family had a hidrotic type of ectodermal dysplasia (ED). Males and females were similarly affected. They had trichodysplasia, with absent eyebrows and eyelashes; normal teeth, on‐ychodysplasia; normal sweating; mild retrognathia; abnormal dermatoglyphics; and mental retardation. Additional variable manifestations included irregular menses, high implanted or prominent ears, café‐au‐lait spot, keratosis pilaris, supernumerary nipple, and mild hearing loss. Their previously undescribed condition could be classified as an ED of 1–3 (trichoonychial) subgroup of group A according to Freire‐Maia's classification and is inherited as an autosomal recessive trait.
Association of distal arthrogryposis, mental retardation, whistling face, and pierre robin sequence: Evidence for nosologic heterogeneity
Authors: Schrander‐Stumpel Constance , Fryns Jean Pierre , Beemer Frits A. , Rive Frans A. 
Published: June 2005

AbstractWe report on 3 unrelated patients with the heterogeneous fetal hypokinesia sequence. They have distal arthrogryposis, severe developmental retardation, facial anomalies as seen in the Freeman‐Sheldon syndrome (“whistling face”), and Pierre Robin sequence. The present cases show a remarkable clinical resemblance to the 3 sibs described by Illum et al. (Illum N, Reske‐Nielsen E, Skovby F, Askjaer SA, Bersen A 1988: Neuro‐pediatrics 19:186–192), where calcium deposits were found in the nervous system and skeletal muscle. The presence of severe to profound developmental retardation in the present 3 patients is equally in favour of a central nervous system abnormality as the pathogenetic basis of the fetal hypokinesia sequence with secondary facial changes and distal arthrogryposis.
Interstitial deletion of the long arm of chromosome 6 associated with absent pulmonary valve
Authors: Horigome Hitoshi , Takano Takako , Hirano Takeki , Kajima Takako , Ohtani Shin‐Ichi 
Published: June 2005

AbstractWe report on a newborn infant with a deletion of 6q and absent pulmonary valve. His chromosome constitution was 46, XY,del (6) (q15q21). To our knowledge this is the first case with such combination. Some of his clinical features were found in common in 2 previous 6q – cases with the same breakpoints.
Huntington disease and childhood‐onset Tourette syndrome
Authors: Kerbeshian Jacob , Burd Larry , Leech Cindi , Rorabaugh Anne 
Published: June 2005

AbstractA 40‐year‐old man with childhood‐onset Tourette syndrome (TS) developed Huntington disease (HD). We believe this to be the first reported case of childhood‐onset TS with adult onset HD. Discovery of other cases with both disorders may provide clues to the pathophysiology of both conditions.
Maternal muscle biopsy in X‐linked recessive centronuclear (myotubular) myopathy
Authors: Breningstall Galen N. , Grover Warren D. , Marks Harold G. 
Published: June 2005

AbstractMuscle biopsy was used to attempt determination of carrier status in mothers and maternal relatives of patients with severe neonatal centronuclear (myotubular) myopathy, an X‐linked recessive disorder. We report findings from muscle biopsies of 3 mothers, one an obligate carrier. All biopsies showed abnormalities of nonspecific character. Whether such abnormalities assist in defining carrier status is uncertain. A more specific tissue marker for this disorder is required before muscle biopsy will facilitate carrier identification.
Risks associated with an elevated amniotic fluid α‐fetoprotein level
Authors: Crandall Barbara F. , Matsumoto Myles 
Published: June 2005

AbstractTwo and two‐tenths percent of 85,000 consecutive amniotic fluid (AF) samples had α‐fetoprotein (AFP) levels ≥ 2.0 MoM. Half measured 2.0–2.4 MoM, and 93% had a normal outcome. Sixty‐seven percent of those with higher levels had abnormalities. A positive acetylcholinesterase (AChE) increased the risk from 67% for levels between 2.0 and 2.4 MoM to 99% at ≥ 5.0 MoMs. After a normal ultrasound and chromosome studies, the risk for a fetal abnormality was 1% for AF AFP measuring 2.0–2.4 MoM and 3% for higher levels.