bluuebunny/crossref_metadata_2025_split huggingface dataset:
Linkage analysis in families with autosomal recessive limb‐girdle muscular dystrophy (LGMD) and 6q probes flanking the dystrophin‐related sequence
Authors: Passos‐Bueno Maria Rita , Terwilliger Joseph , Ott Jürg , Vainzof Mariz , Love Donald R. , Davies Kay E. , Zatz Mayana 
Published: June 2005

AbstractThe clinical similarity with the X‐linked muscular dystrophies and the uniqueness of the homology between the DMD‐like and the 1.8 kb sequeces at the carboxyterminal domain of the dystrophin gene led to the suggestion that this 6q sequence might be a strong candidate for one of the autosomal recessive muscular dystrophies. Thus, we tested, through linkage analysis, if 6q probes flanking the dystrophin‐homologous sequence are linked to the gene responsible for limb‐girdle dystrophy (LGMD).A total of 226 individuals (57 patients and 169 unaffected relatives) from 19 large unrelated Brazilian families was studied.Results of two‐point aalysis excluded linkage with MYB (6q22–23) and ESR (6q24–q27) at θ=0.10 and with TCP1 (6q25–q27) at θ=0.05, indicating that the LGMD gene is not in the 6q23–q27 region. Therefore, the dystrophin‐homologue sequence is not the gene responsible for LGMD.
XLMR genes: Update 1990
Authors: Neri Giovanni , Gurrieri Fiorella , Gal Andreas , Lubs Herbert A. 
Published: June 2005

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

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

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

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

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

AbstractSegregation analysis of the fragile‐X [fra(X)] syndrome uncovered an unexpected 20% excess of normal males among sibships by Sherman et al. (Sherman SL, Morton NE, Jacobs PA, Turner G [1984]. Ann Hum Genet 48:21–37; Sherman SL, Jacobs PA, Morton NE, Froster‐Iskenius U, Howard‐Peebles PN, Nielsen KB, Partington MW, Sutherland GR, Turner G, Watson M [1985]: Hum Genet 63:289–299). This result predicts that about 17% (1/6) of normal sons of carrier fra(X) females will be non‐penetrant. A way to test this prediction is by DNA markers. We analyzed DNA samples from 100 families with a set of flanking DNA markers linked to the fra(X) locus. Ten of 51 (19.6%) normal brothers, doubly informative and non‐recombinant for flanking DNA markers, were found to be non‐penetrant males. This result closely confirms the predictions of the segregation analysis indicating that about 1/6 of normal brothers are non‐penetrant carrier males.The use of DNA markers to identify non‐penetrant brothers and grandfathers can help to clarify the inheritance of the fra(X) mutation and be of considerable clinical usefulness. Using DNA markers, it was possible to study grandparental transmission in 71 of the families. In 39 families, DNA analysis confirmed the apparent pattern of inheritance. In 18 families, the grandparents had a single daughter with affected children. Of these, a new mutation at the time of their daughters conception was possible in 15 and quite likely in 3. In 14 families with 2 or more daughters with affected fra(X) offspring, the grandparents had no affected sons or other relatives known to be positive for fra(X). In 6 of these families, only 2 daughters had affected sons and transmission was found to be from a non‐penetrant grandfather in 3. In the other 8 families, 3 or more daughters had affected sons and the grandfather was found to be a transmitting male in 7. These results have allowed guidelines to be formulated to assist with genetic counseling in the use of DNA markers in detecting non‐penetrant males.
Linkage analysis in the fragile X syndrome using multiple distal Xq polymorphic DNA markers
Authors: Glass I. A. , Pirrit L. A. , White E. M. , Bell M. V. , Davies K. E. , Cockburn F. , Connor J. M. 
Published: June 2005

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

AbstractDuring the past 4 years (1985–1989), we have analyzed 171 cases in 50 fragile X [fra(X)] families by DNA linkage methods. Most (140 cases; 81%) were for carrier detection, both female (98 cases; 57%) and male (41 cases; 24%). Women who were obligate carriers of the fra(X) mutation accounted for an additional 6 “prior‐to‐pregnancy” cases. Four pregnancies have subsequently occurred with 3 having been successfully monitored (one male, 2 females). One pregnancy miscarried early prior to testing. Prenatal diagnoses (26 cases; 15%) accounted for the remainder of cases (15 males, 11 females). These will be discussed in the companion paper by Shapiro et al. (Am J Med Genet, 1991).A diagnosis in the cytogenetically uninformative carrier cases was reached in >75% of analyses with a panel of 5 probes: 3 proximal (F9, DXS105, DXS98) and 2 distal (F8, DXS52). Five additional probes, 3 proximal (DXS10, DXS51, DXS102) and 2 distal (DXS15, DXS33), were used in cases that were resistant to analysis with the standard panel. In 60% of cases, flanking markers were identified (proximal and distal). Given this panel, only 5% of cases did not have any informative markers identified. Thus, molecular methods can provide a useful adjunct to cytogenetic analysis in most situations.An unusual association between the rare allele (A1) of DXS10 with the X chromosome carrying the fra(X) mutation was observed. This occurred in both male and female carriers in the uppermost generation tested. The basis for this association is uncertain at the present time.
Carrier detection of the fragile X syndrome using flanking loci DXS98, DXS105, and DXS304
Authors: Dahl Niklas , Malmgren Helena , Pettersson Ulf , Holmgren Gösta , Seemanová Eva , Gustavson Karl‐Henrik 
Published: June 2005

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

AbstractRecently some of us cloned a new probe RN1 (DXS369), which appears a close marker for the fragile X locus (FRAXA) [Oostra et al.: Genomics 1990]. We present here new evidence for its physical and genetic mapping in the DXS98—FRAXA interval. We used 2 different somatic cell hybrid lines with breakpoints in the Xq27–q28 region: L10B Rea and PeCHN, and we established the order: (DXS105, DXS98)‐L10B Rea‐DXS369‐PeCHN‐ (DXS304, DXS52). We detected an additional TaqI RFLP at the DXS369 locus which increases its informativeness up to 57%. Two point linkage analysis in a large set of families gave high lod scores for the FRAXA‐DXS369 linkage (zΘ = 10.1 at Θ = 0.044) and for DXS369‐DXS304, a marker distal to FRAXA (z = 19.2 at Θ = 0.070). By multipoint analyses we established the localization of DXS369 in the DXS98‐FRAXA interval.DXS369 is a much closer proximal marker for FRAXA than DXS105 or DXS98 and any new probe mapping between the breakpoints in L10B Rea and PeCHN will be of potential interest as a marker for FRAXA.
Linkage in fragile X families of three distal flanking markers: ST14, DX13, and F8
Authors: Brown W. Ted , Gross Anne C. , Goonewardena Ponmani , Ferrando Charles , Dobkin Carl , Jenkins Edmund C. 
Published: June 2005

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

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

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

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

AbstractWe have used the polymerase chain reaction (PCR) to analyze the 50 base pair (bp) insertion/deletion polymorphism in the coagulation factor 9 gene. This procedure is particularly applicable for DNA marker studies in fragile X families. The polymorphism, which can also be detected in Dde I digestions, was detected by the amplification of fragments of 298 and 348 bp. The alleles were distinguished directly by agarose gel electrophoresis. PCR detection of this polymorphism is much simpler, more accurate, and quicker than conventional analysis.
Possible Erasure of the Imprint on a Fragile X Chromosome When Transmitted by a Male
Authors: Laird Charles D. 
Published: June 2005

AbstractAlthough most males with the fragile‐X [fra(X)] syndrome do not reproduce, there are 2 published pedigrees that include affected males who have daughters and who thus appear to have transmitted the fragile‐X chromosome to their progeny. In addition, one published fra(X) pedigree includes an apparently normal male who expresses cytogenetically the fra(X) site at high frequency and who has 3 daughters. In the 6 daughters of these 3 males, there is little or no cytogenetic expression of the fra(X). I interpret these pedigrees within the context of my X‐inactivation imprinting model of the fra(X) syndrome (Genetics 117:587–599): the cytogenetic manifestation of the imprinted state of the mutant fra(X) chromosome [high percentage of cytogenetic expression] is no longer present in daughters of imprinted males. I propose that the imprinted state is erased when an imprinted fragile‐X chromosome is passed through a male. Such erasure in the gender opposite to the gender that established the imprint is in accord with other examples of chromosome imprinting in mammals. Additional data from unpublished fra(X) pedigrees are requested.
Guidelines for the Preparation and Analysis of the Fragile X Chromosome in Lymphocytes
Authors: Jacky P. B. , Ahuja Y. R. , Anyane‐Yeboa K. , Breg W. R. , Carpenter N. J. , Froster‐Iskenius U. G. , Fryns J.‐P. , Glover T. W. , Gustavson K.‐H. , Hoegerman S. F. , Holmgren G. , Howard‐Peebles P. N. , Jenkins E. C. , Krawczun M. S. , Neri G. , Pettigrew A. , Schaap T. , Schonberg S. A. , Shapiro L. R. , Spinner N. , Steinbach P. , Vianna‐Morgante A. M. , Watson M. S. , Wilmot P. L. 
Published: June 2005

AbstractThe following guidelines were adopted by an Ad Hoc Committee convened at the Fourth International Workshop on the Fragile X Syndrome and X‐Linked Mental Retardation to establish minimum cytogenetic standards for the preparation and analysis of the fragile X chromosome. The intention of the committee was to develop and provide practical standards for the routine cytogenetic detection of the fragile X. The guidelines describe reasonable criteria for effective tissue culture methods for eliciting the Xq27.3 fragile site in vitro and for the analysis of such chromosome preparations.
Mental impairment in cytogenetically positive fragile X females
Authors: Cronister Amy , Hagerman Randi J. , Wittenberger Michael , Amiri Khaled 
Published: June 2005

AbstractPrenatal diagnosis is now available to fragile X (fra[X]) syndrome families and has proven reliable when testing male fetuses. It has been reported that approximately one‐third of heterozygous fra(X) females demonstrate mental impairment. Based on this, families usually continue pregnancies involving a female fetus. The purpose of this study is to investigate whether a 35% risk for mental impairment is appropriate when counseling heterozygous women carrying fra(X)‐positive female fetuses. Forty‐three cytogenetically positive (≥2%) daughters of known fra(X) carrier women were ascertained postnatally in an unbiased fashion. Their mother's carrier status was determined on the basis of at least one son with Martin‐Bell syndrome. In addition to peripheral blood cytogenetic studies, all daughters had cognitive testing to determine full‐scale IQ. In this study, 55.8% (24/43) were mentally impaired (IQ <85) compared with the expected 35%. Of these, 42% were mentally retarded (IQ <70). Although we do not know the correlation between percent fragility by peripheral blood compared with the percent fragility by amniocentesis or CVS, we assume that they are relatively comparable such that a female who is positive with ≥2% fragility would probably be positive by all methods. This report suggests that the penetrance of mental impairment in females with a percent fragility of ≥2% may be as high as 55%. Further studies are necessary to clarify this issue so that accurate information can be given in genetic counseling.
Interstitial 15q deletion without a classic Prader‐Willi phenotype
Authors: Galán Francisco , Aguilar María Soledad , González Juan , Clemente Fernando , Sánchez Rafael , Tapia Manuel , Moya Manuel 
Published: June 2005

AbstractWe report on a newborn boy with pronounced hypotonia, cryptorchidism, minor facial anomalies, congenital heart defect, neurologic anomaly, deafness, renal anomaly, and bifid uvula. The patient has a de novo proximal interstitial deletion of chromosome 15 reaching to band q14, larger than that usually seen in Prader‐Willi and Angelman syndromes.
The cardio‐facio‐cutaneous (CFC) syndrome and Noonan syndrome: Are they the same?
Authors: Fryer A. E. , Holt P. J. , Hughes H. E. 
Published: June 2005

AbstractThe distinction between the cardio‐facio‐cutaneous syndrome (CFC) and the Noonan syndrome (NS) has been based on the presence of a characteristic facies, abnormal hair and skin, and sporadic occurrence. However, all reports of the CFC syndrome comment on the similarity between it and NS, and its sporadicnature is now debatable. This report demonstrates the evolution of the clinical phenotype in a patient with the CFC syndrome and prompts us to question the validity of separating CFC from NS.
Prevalence study of Rett syndrome in North Dakota children
Authors: Burd Larry , Vesley Barbara , Martsolf John T. , Kerbeshian Jacob 
Published: June 2005

AbstractService providers for children in the state of North Dakota were surveyed to determine the prevalence rate of Rett syndrome (RS). Five patients with definite RS were identified in a population of 203,801 children (98,932 girls) 0–18 years of age yielding a prevalence rate of RS of 1 in 40,760 in North Dakota children. For girls the rate of RS is 1 in 19,786. Similar surveys of other states using comparable modes of ascertainment will be important as points of comparison for prevalence rates of RS.