bluuebunny/crossref_metadata_2025_split huggingface dataset:
Mental retardation, acromegalic face, and megalotestes in two half‐brothers: A specific form of X‐linked mental retardation without fra(X) (q)?
Authors: Tariverdian G. , Froster‐Iskenius U. , Deuschl G. , Wolff G. 
Published: June 2005

AbstractWe describe a family with two half‐brothers affected with severe mental retardation. The phenotype in the affected individuals is characterized by apparent acromegaly, profound mental retardation, and hyperactivity. The mother has analogous but less severe facial anomalies and mild mental impairment. Screening for fra(X) (q) was negative in peripheral lymphocytes using methotrexate for fra(X) enhancement. The clinical findings in our patients are similar to those described by Fryns et al. [1986] in two patients with acquired lesions of the central nervous system. CT investigations in one of our patients showed areas of hyperdensity in the pontine region and a small subarachnoid cyst. The pedigree suggests X‐linked inheritance. The association of apparent acromegaly, CNS anomalies, megalotestes, and mental retardation in this family supports the hypothesis that a distinct syndrome may exist with phenotype anomalies more severe than those characteristic for the Martin‐Bell syndrome but without fragile X.
Unique X‐linked mental retardation syndrome with fingertip arches and contractures linked to Xq21.31
Authors: Miles Judith H. , Carpenter Nancy J. 
Published: June 2005

AbstractWe studied 10 members of a 4 generation Missouri kindred with a dominant mental retardation syndrome with increasing severity in males. The 21 year‐old propositus presented with severe mental retardation, microcephaly, asymmetric face, exotropia, hypogonadism, joint hypermobility, rocker bottom feet, and 10 low digital arches. Two brothers and a male cousin had similar features. The mother, sister, niece, maternal aunt, female cousin, and grandmother were examined and each had 8 to 10 low digital arches. Five of the women had exotropia and one had pes cavus feet. Chromosome analysis for fragile X in multiple relatives was normal.To determine the likelihood that this was an X‐linked syndrome, DNA from relatives was hybridized to probes which detect 13 different loci spanning the X‐chromosome. A peak LOD score of 2.78 at θ equal to 0.0 was calculated for the syndrome locus and DXYS1 (pDP34). The more distal Xq loci showed increasing recombination with the syndrome locus. These results are consistent with location for this syndrome near Xq21.31, the chromosomal locus for DXYSI.
Gene localization in a family with X‐linked syndromal mental retardation (Prieto syndrome)
Authors: Watty Anke , Prieto Félix , Beneyto Magdalena , Neugebauer Meinhard , Gal Andreas 
Published: June 2005

AbstractA mapping study was performed on a 3‐generation Spanish family with X‐linked syndromal mental retardation. Affected males have a typical facial appearance, ear malformations, abnormal growth of teeth, clinodactyly, dimpled skin at the lower back, and patellar luxation. In pneumoencephalography a marked subcortical cerebral atrophy was evident. In the linkage studies with polymorphic DNA markers, no recombination was found between the disease locus and the loci OTC and DXS148, both assigned to Xp21.1. One or more recombinants were observed between the disease locus and loci from the distal part of Xp and the pericentromeric region. Close linkage to loci of Xq has also been excluded. The analysis of multiple informative meioses suggests that the disease locus maps between DXS255 (Xp11.22) and DXS84 (Xp21.1) on Xp.
Heterozygous fragile X female: Historical, physical, cognitive, and cytogenetic features
Authors: Cronister Amy , Schreiner Rebecca , Wittenberger Michael , Amiri Khaled , Harris Keri , Hagerman Randi J. 
Published: June 2005

AbstractHistorical, physical, cognitive, and cytogenetic data were documented in 105 heterozygous fragile X [fra(X)] females and 90 controls in a prospective fashion. For comparisons, we divided heterozygotes and controls into those with cognitive impairment (IQ <85) and normal IQ (IQ ≥ 85). The only finding that was significantly more frequent in impaired heterozygotes compared with impaired controls χ2 analysis was shyness. Features that were more frequent in normal IQ heterozygotes compared with normal controls were voluntary thumb dislocation and hyperextensible metacarpal‐phalangeal (MP) joints. Comparisons among heterozygotes demonstrated more math problems, hand biting, strabismus, higharched palate, hyperextensible finger joints, and flat feet in impaired heterozygotes than in normal heterozygotes. Premature menopause was present in 8 of 61 normal heterozygotes and in none of the impaired heterozygotes. A multiple regression analysis demonstrated a significant inverse correlation between the percent fragility and IQ for the heterozygotes as a group. However, no correlation existed between IQ and fragility when the percent fragility was 2% or greater. However, a higher percentage of fragility was positively correlated with the total number of physical findings present.
DNA linkage analysis of 26 families with fragile X syndrome
Authors: Carpenter Nancy J. 
Published: June 2005

AbstractLinkage data using the markers F9 (factor IX), DXS105 (cX55.7), DXS98 (4D‐8), DXS52 (St14), DXS15 (DX13), and DXS134 (cpX67) are presented from 26 pedigrees segregating with fragile X (fra[X]) syndrome. Cytogenetic and DNA data were combined in 2‐point linkage analysis for the estimation of lod scores and carrier probabilities in potential carriers. Recombination fractions (θ) corresponding to the maximum lod scores (Ẑ) were obtained for F9 (Ẑ = 2.78, θ = 0.15), DXS105 (Ẑ = 1.72, θ = 14), DXS98 (Ẑ = 3.74, θ = 0.00), DXS52 (Ẑ = 3.53, θ = 0.17), DXS15 (Ẑ = 4.03, θ = 0.11), and DXS134 (Ẑ = 2.12, θ = 0.16) and for the fragile X locus (FRAXA). Recombination fractions between marker loci in the families are also presented. Discordance between the results of cytogenetic and DNA analyses in 2 potential carrier females was investigated by reexamination of the fragile site expression and was concluded to be due to the expression of the common fragile site at Xq27.2.
Linkage analysis of the fragile X syndrome using a new DNA marker U6.2 defining locus DXS304
Authors: Goonewardena Ponmani , Brown W. Ted , Gross Anne C. , Ferrando Charles , Dobkin Carl , Romano Valentino , Bosco Paolo , Ceratto Nadia , Pettersson Ulf , Dahl Niklas 
Published: June 2005

AbstractA new RFLP marker U6.2 defining the locus DXS304 was recently mapped to the distal long arm of the X chromosome. In the present study we report the results of genetic linkage analysis of 13 fragile X [fra(X)] families that were informative for the new marker. Analysis of the recombinants for F9‐FRAXA, DXS105‐FRAXA, DXS98‐FRAXA, DXS52‐FRAXA, DXS15‐FRAXA, and F8C‐FRAXA, places DXS304 distal and near to the FRAXA locus. Combined with results from previous studies, our results support the order Xcen.‐F9‐DXS105‐DXS98‐FRAXA‐DXS304‐DXS52‐DXS15‐F8C‐Xqter. Close linkage was observed between DXS304 and the disease locus with a peak lod score of 5.12 at Θ = 0.04 from the present study and, with a peak lod score of 17.45 at Θ = 0.035 when our data are combined with published data from 2 other studies. The present study confirms that U6.2 is useful for prenatal diagnosis and carrier testing in families affected by fra(X) syndrome.
Mapping of a cerebellar degeneration related protein and DXS304 around the fragile site
Authors: Hirst M. C. , Bell M. V. , MacKinnon R. N. , Watson J. E. V. , Callen D. , Sutherland G. , Dahl N. , Patterson M. N. , Schwartz C. , Ledbetter D. , Ledbetter S. , Davies K. E. 
Published: June 2005

AbstractWe have localized the gene encoding a cerebellar degeneration related (CDR) protein to a region proximal to the fragile site close to DXS98 and DXS105. This gene is polymorphic with the enzyme RsaI and therefore also provides a new genetic marker in this region. We have refined the localization of the locus DXS304 distal to the breakpoint in a patient suffering from Hunter disease. This confirms the localization of DXS304 distal to the fragile site previously suggested by linkage studies and localizes the fragile X mutation to a relatively small region between the Hunter breakpoint and the breakpoint in another hybrid B17.
Cytogenetically negative, linkage positive “fragile X” syndrome
Authors: Brooks Susan Sklower , Cohen Ira , Ferrando Charles , Jenkins Edmund C. , Brown W. Ted , Dobkin Carl 
Published: June 2005

AbstractWe investigated the family of a 3‐year‐old boy with manifestations of the Martin‐Bell syndrome (MBS). His 17‐year‐old cousin had classic manifestations of MBS and was fragile X [fra(X)] positive. The 3‐year‐old boy was fra(X) negative. Linkage analysis with probes flanking the fra(X) region indicated that these cousins had the same X chromosome inherited from a normal grandfather. The DNA and cytogenetic analyses suggest that limitations in the ability to detect the fra(X) mutation cytogenetically may be responsible for fra(X) negative MBS; or, alternatively, that a crossover occurred between a locus determining the MBS phenotype and one determining fra(X) expression.
Cloning the ends of size selected Sfi I fragments
Authors: Nolin Sarah L. , Dobkin Carl S. 
Published: June 2005

AbstractAs an initial step in the physical mapping of the fragile X region a library of Sfi I ends was constructed from the size class of human Sfi I DNA fragments, which includes the fragment with the locus DXS105. Since Sfi I recognizes the sequence GGCCNNNNNGGCC and leaves a 3 base indeterminate “sticky” end, we used a mixture of 64 synthetic deoxynucleotide oligomers to modify these ends for cloning. The oligomers were of the general form AATTNNN. Ligation of these heptamers to the indeterminate Sfi I ends converted them to the EcoR I sticky end. A suppressor tRNA gene was ligated onto this end as a selectable marker and the DNA was cloned in the lambda phage vector Charon 21A. Analysis showed that clones selected for the presence of the tRNA gene contained Sfi I ends. Because this library was constructed from a specific size class of fragments, it was very reduced in complexity. This will simplify the process of identifying the clone which contains the end of the DXS105 fragment. The use of this strategy for chromosome “jumping” is discussed.
New somatic cell hybrids for physical mapping in distal Xq and the fragile X region
Authors: Ledbetter Susan A. , Schwartz Charles E. , Davies Kay E. , Ledbetter David H. 
Published: June 2005

AbstractSomatic cell hybrids were constructed from 3 patients carrying X chromosome abnormalities with breakpoints in distal Xq: (1) 94‐3, from a patient with 46, XX, t(X;15)(q25 or q26;q25), (2) 8121‐A1, from a patient with 46, X, del(X)(q26), and (3) 2384‐A2, from a patient with 46, X, del(X)(q27). The breakpoint of patient 94 is proximal to HPRT in q26, a significant distance from the fragile X locus. The breakpoint of patient 8121 is distal to F9, but proximal to DXS98, and is thus proximal to the fragile site region. The breakpoint of 2384 is distal to DXS98 but proximal to DXS52, placing it within the region of the fragile site. Use of these physical mapping reference points will aid in the rapid localization of new DNA markers to distal Xq and the fragile X region.
Effect of X inactivation on fragile X frequency and mental retardation
Authors: Rosenberg Carla , Vianna‐Morgante Angela M. , Otto Paulo A. , Navajas Leda 
Published: June 2005

AbstractThe probability of a heterozygote being affected was estimated from the distribution of frequencies of early‐replicating fragile X [fra(X)] chromosome in normal and mentally retarded heterozygotes, taking into account the prior probabilities of 0.35 for mental retardation and 0.65 for normality. The estimated probability of a heterozygote with 100% early‐replicating fra(X) being mentally retarded was 78%, which coincides with the value of penetrance in males. Therefore, the manifestation of retardation in females seems to differ from that in males due solely to X inactivation. The frequencies of early‐replicating fra(X) were significantly increased among the heterozygotes with the highest frequencies of fra(X) both in the normal group and in the mentally retarded. The mean frequencies of early‐replicating fra(X) were 0.42 and 0.68 for normal and mentally retarded heterozygotes, respectively. Considering the overall frequency of retarded heterozygotes as 0.35, the mean frequency of early‐replicating fra(X) obtained for all heterozygotes was 0.51, which is in accordance with the hypothesis of random X inactivation. Thus the fragile site appears to have equal chances of being detected when located either on the early‐ or on the late‐replicating X. This leads to the conclusion that the frequency of the fragile site is a consequence of the proportion of cells with the active Martin‐Bell syndrome (MBS) gene and not the result of a better visualization of the site on the early‐replicating X.
Fragile Xq27 in somatic cells derived from different tissues
Authors: Webb T. 
Published: June 2005

AbstractPrenatal diagnosis for the Martin‐Bell syndrome resulted in the detection of 4 fragile X‐positive male fetuses and 2 female fetuses. Studies carried out on monolayer cultures derived from various tissues from these show that fra‐Xq27 can be ascertained in cells from testis, lung, kidney, skin, ovary, and muscle. This suggests that the fragility of the X chromosome may be present in all somatic cells. There appears to be no strong correlation between the level of marker detected and the involvement of the tissue from which the cells were derived in the manifestation of the syndrome. The level of fra‐X is dependent rather more on culture conditions than on cell type except for lymphocytes, in which detection is easier.
Distribution of diploidy, polyploidy, and endoreduplication in fra(X) positive and negative lymphocytes, amniocytes, and chorionic Villi
Authors: Jenkins Edmund C. , Sanz Maureen M. , Ray James H. , Stark‐Houck Sandra L. , Brown W. Ted 
Published: June 2005

AbstractExpression of fragile X [fra(X)] (q27.3) and en‐doreduplicated metaphases have been reported in methotrexate‐treated (MTX) fra(X) cultures (Kerem B, Biotein R, Schaap T [1988]: Chromosoma 97: 6–10). Further, new data (Kimchi‐Sarfaty C, Goitein R, Kerem B, Werner M, Medan B, Schaap T [1991]: Am J Med Genet, this issue) indicate that MTX may specifically induce polyploidy and endo‐reduplication in cells with the fra(X) mutation. To confirm and extend these results, we have studied short‐term lymphocyte cultures incubated in M199, a folate deficient system, and RPMI‐1640 in the presence and absence of 5‐fluorodeoxyuridine (FUdR) exposure during the last day of a 4 day culture. No endo‐reduplicated cells were seen under these conditions and there was no change in the level of polyploidy. We also studied the distribution of polyploid and endoreduplicated cells in amniotic fluid and chorionic villus sample cultures from one fra(X) positive and 4 at‐risk specimens. No increase in the incidence of polyploidy or endoreduplication was observed in cultures exposed to MTX for both 24 and 48 hours from a fra(X) positive amniotic fluid case. Cytogenetic results were fra(X) negative for the remaining 4 cases tested. There was significant discordance between our findings and those expected based on MTX‐induced increased frequencies of polyploidy and endoreduplication. Thus, our studies do not confirm the reported correlation between the presence of FRAXA and increased frequencies of polyploidy and endoreduplication in MTX‐exposed amniocyte cultures and there was no evidence for increased levels of polyploidy and endoreduplication in short‐term fra(X) lymphocyte cultures exposed to non‐MTX fra(X) induction.
Distribution of autosomal fragile sites in specimens cultured for prenatal fragile X diagnosis
Authors: Krawczun Michael S. , Jenkins Edmund C. , Duncan Charlotte J. , Stark‐Houck Sandra L. , Kunaporn Suphat , Schwartz‐Richstein Carol , Gu Hong , Brown W. Ted 
Published: June 2005

AbstractWe reviewed the distribution of autosomal fragile sites (FS) and spontaneous chromosome breaks or gaps (CB) at chromosome locations other than those recognized as FS from 100 amniotic fluid samples (AF), 19 chorionic villus samples (CVS), and 5 percutaneous umbilical blood samples (PUBS) referred for fragile X [fra(X)] analysis. We present data on the degree of expression of autosomal fragility in AF, CVS, and PUBS samples, and the relationship between degree of expression and induction system. The most common observed FS were: 3p14, 9p32, and 6q26 in AF; 9q32, 3q27, and 8q22 in CVS; and 3p14, Xq22, and 16q23 in PUBS cases. Distribution of FS and CB, when compared by induction system, was not found to be identical. Our data also indicate that the presence of any particular FS cannot be used as an indicator for the effectiveness of the fra(X) induction system in prenatal samples.
SV40‐transformed fragile (X) amniocytes
Authors: Jenkins Edmund C. , Brooks Steven E. , Stark‐Houck Sandra L. , Duncan Charlotte J. , Brooks Susan L. Sklower , Brown W. Ted 
Published: June 2005

AbstractWe report SV‐40 transformation of female and male fragile X [fra(X)] amniocytes. In the transformants, fra(X) (q27.3) was detected in the 7th passage (9 cell generations) in fra(X) female amniocytes. It was conserved until at least the 20th passage (42 cell generations) although the frequency was reduced or became difficult to detect due to karyotypic evolution in the later generations. Similarly, for the male fra(X) amniocyte line, fra(X) was demonstrated at the 2nd passage (3 cell generations) and persisted until at least the 13th passage (29 cell generations). The prolonged period of reproductive potential of these transformed lines ranging from at least 29–42 generations suggests that the cryopreservation of significant quantities of early passage fra(X) transformed amniocytes will assure a reliable and continuous supply of positive control cells. These lines may be used for fra(X) prenatal diagnostic studies thereby improving the ability to quality control the particular fra(X) induction system being used.
Syntactic delay and pragmatic deviance in the language of fragile X males
Authors: Sudhalter Vicki , Scarborough Hollis S. , Cohen Ira L. 
Published: June 2005

AbstractThe expressive language of 19 fragile X [fra(X)] males with chronological ages between 5 and 36 years and Vineland Adaptive Behavior Scores between 21 and 79 was examined for syntactic as well as pragmatic proficiency. The production of deviant repetitive language was observed with this group, corroborating the results of an earlier study with a smaller sample of fra(X) males. In contrast, when 2 syntax scores, mean length of utterance (MLU), and Index of Productive Syntax (IPSyn) were derived from naturalistic language observations, the relation of complexity to length was observed to be very similar to the known relationship of these 2 facets of syntactic ability in normal preschoolers. These results, and the absence of correlations between syntactic scores and proportions of deviant repetitive language are consistent with the notion that the syntactic development of fra(X) males is typically delayed rather than deviant. For effective assessment and remediation of communicative problems associated with the syndrome to be developed, it is argued, language must be considered as a combination of competencies rather than as a unitary skill.
Epilepsy and fragile X syndrome: A follow‐up study
Authors: Musumeci S. A. , Ferri R. , Elia M. , Colognola R. M. , Bergonzi P. , Tassinari C. A. 
Published: June 2005

AbstractThis paper describes EEG and clinical findings resulting from a follow‐up investigation in a group of 18 males with fragile X syndrome, in whom a characteristic paroxysmal EEG pattern was previously described. The following types of evolution were observed: (1) disappearance of the pattern (with a gradual lowering of the amplitude of spikes and in some cases with asynchrony between the two hemispheres); (2) disappearance of the quasirhythmic centrotemporal spikes and persistence of bisynchronous polyspike and wave complexes in the temporo‐parieto‐frontal regions; and (3) persistence of the previously observed pattern. These results confirm the already observed similarity between this condition and the benign childhood epilepsy with centrotemporal spikes, also from the maturational point of view; on the other hand, they also indicate some difference (i.e., mental retardation, slow background EEG activity, brain atrophy). Moreover, these findings are encouraging for the possible development of research in the field of molecular genetics in epilepsy, because they provide a precise site of investigation on the X chromosome.
New multiple congenital anomalies syndrome in a stillborn infant of consanguinous parents and a prediabetic pregnancy
Authors: Van Allen Margot I. , Myhre Selma 
Published: June 2005

AbstractWe report on a term stillborn female infant with multiple congenital anomalies (MCA) which have not previously been reported as occurring together. The malformations include a first and second branchial arch sequence, ectopia cordis with congenital heart defect, caudal “regression” sequence with absent sacrum and hypoplastic right femur, ectrodactly, left radial abnormality, islet cell hyperplasia, and skin lesions. The pregnancy was complicated by abdominal cramping with exercise, heavy vaginal bleeding, maternal obesity, and a normal screening glucose tolerance test at 6 months gestation. The infant was born to 20‐year‐old G3P1SAB2 Mexican‐American parents who are first cousins. There was strong maternal family history of adult‐onset diabetes.The malformations have some findings in common with those seen in infants of diabetic mothers. Structural defects similar to, but not inclusive of, those in our infant have been reported in 2 sibs born to a prediabetic mother with a first cousin marriage as well as in focal dermal hypoplasia. Parental consanguinity is suggestive of an autosomal recessive disorder. Alternatively, it may represent a combined multifactorial effect making the conceptus more sensitive to metabolic teratogens and thus placing it at increased risk for disruption of normal development.
Ectrodactyly, cleft lip/palate syndrome
Authors: Rodini Elaine S. O. , Freitas J. A. S. , Richieri‐Costa A. 
Published: June 2005

AbstractWe report on a Brazilian boy with ectrodactyly, cleft lip/palate, and abnormal pinnae. The clinical aspects involving this patient strongly suggest those reported by Lewis and Pashayan in 1981. Clinical and genetic aspects are discussed.
Floating‐Harbor syndrome and celiac disease
Authors: Chudley Albert E. , Moroz Stanley P. 
Published: June 2005

AbstractWe report on a 17‐year‐old young woman with a speech impediment, developmental delay, short stature, and facial anomalies consistent with the Floating‐Harbor syndrome (FHS). In addition, she has clinical and histological evidence of celiac disease, which was observed in 1 of the 6 previously reported cases of FHS, suggesting a possible association between the 2 conditions or pleiotropism of a presumed autosomal recessive disorder.