bluuebunny/crossref_metadata_2025_split huggingface dataset:
Evaluation of school children at high risk for fragile X syndrome utilizing buccal cell FMR‐1 testing
Authors: Hagerman Randi J. , Wilson Philip , Staley Louise W. , Lang Kirsten A. , Fan Tammi , Uhlhorn Cynthia , Jewell‐Smart Sabrina , Hull Claire , Drisko Jodi , Flom Kerry , Taylor Annette K. 
Published: June 2005

AbstractWe describe a pilot project utilizing saliva to identify the FMR‐1 mutation in high‐risk special education students from four public school districts in Colorado. The program included presentations to special education teachers regarding fragile X syndrome, parental consent for testing, completion of a behavior checklist by the teachers, identification of special education students at high risk for fragile X syndrome, subsequent brief examination of face and hands, collection of a saliva sample by either Gatorade swish or brushing of the inside of the cheek, and analysis for the FMR‐1 mutation by PCR. Equivocal samples were studied by direct DNA testing using Southern blot analysis, and abnormal results were confirmed by a blood analysis for the FMR‐1 mutation. Mutant individuals received genetic counseling and medical and educational assessments to optimize treatment and intervention.This pilot project was met with enthusiasm by the schools. Of the first 439 students evaluated, 68% were male with an average age of 7.75 years; 13% were mentally retarded or autistic. Most students referred for the evaluation were learning disabled (51%) and/or had an Attention Deficit Hyperactivity Disorder (ADHD) (35%). The overall prevalence of the FMR‐1 mutation was 5 of 439 or 1.1%. This relatively low yield is probably due to the high number of non‐retarded but learning disabled students tested. Of the mentally retarded patients tested, 3.5% were positive for the FMR‐1 mutation; however, of the non‐retarded or learning disabled patients, only 0.79% were FMR‐1 positive. The high‐risk criteria have been strengthened with a focus on mentally retarded individuals in an effort to increase our yield of affected individuals in the future. © 1994 Wiley‐Liss, Inc.
Prediction of mental status in carriers of the fragile X mutation using CGG repeat length
Authors: Smits Arie , Smeets Dominique , Hamel Ben , Dreesen Jos , de Haan Anton , van Oost Bernard 
Published: June 2005

AbstractFor genetic counseling in fragile X (fra(X)) families, it is important to know the diagnostic impact of the CGG repeat length in carriers of the fragile X mutation. We have analyzed the CGG repeat length in 106 males and 73 females who had inherited the maternal fra(X) mutation. The sensitivity, specificity, and predictive value of the CGG repeat analyses, as measured on Southern blots of PstI/EcoRI digests, were calculated. In males the sensitivity, specificity and negative predictive value were 99%, 100% and 94%; respectively. In females the specificity (60%) and, consequently, the positive predictive value (82%) was reduced. Therefore, it remains impossible to predict accurately whether a female fetus demonstrating a full mutation will be affected. On the other hand, the negative predictive value of the CGG test in females was 100%. We have no evidence, as yet, that for female carriers with the full mutation, cytogenetic analysis is of additional value to predict the mental status. However, we have observed one mentally retarded fra(X) case with extreme mosaicism in which a typical premutation fragment was the predominant DNA species. Therefore, until more data and better DNA tests are available, we would like to advocate additional cytogenetic investigation if in a fetus a CGG repeat length in the premutation range is found. © 1994 Wiley‐Liss, Inc.
Direct mutation analysis of 495 patients for fragile X carrier status/proband diagnosis
Authors: Kaplan Gail , Kung Melissa , McClure Melody , Cronister Amy 
Published: June 2005

AbstractWith the cloning of the FMR‐1 gene, direct mutation analysis is possible for fragile X syndrome. We have analyzed 495 patients using the StB12.3 probe/EcoRI/EagI system of Rousseau et al. [N Engl J Med 325:1673–1681, 1991] and 167 of these also with PCR analysis according to Brown et al. [JAMA 270:1569–1575, 1993]. For 28 patients requesting carrier status due to a family history of fragile X, 10 were shown to have either premutations or full mutations; for the remainder with varied backgrounds, 1 in 182 was shown to carry a premutation. For proband diagnosis, 7 of 14 with a fragile X family history carried a full mutation; 11 of 271 with other family histories carried the full mutation. © 1994 Wiley‐Liss, Inc.
Characteristics of the transmission of the FMR1 gene from carrier females in a prospective sample of conceptuses
Authors: Sherman S. L. , Maddalena A. , Howard‐Peebles P. N. , Brown W. T. , Nolin S. , Jenkins E. , Schwartz C. , Tarrelton J. , Shapiro L. R. , Smits A. P. T. , van Oost B. A. , Youings S. , Jacobs P. A. , Martinez F. , Barnicoat A. , Hockey A. , Staley L. , Hagerman R. , Kennerknecht I. , Steinbach P. , Barbi G. , Filippi G. , Grasso M. , Taylor S. A. M. , Robinson H. , Webb T. , Broome D. , Dixon J. , Ferreira P. , Gustavson K.‐H. , Meyer J. L. , Pai G. S. 
Published: June 2005

AbstractThe Prospective Study of the Fragile X Syndrome is a large collaborative effort designed to collect prospective data on the pregnancy outcomes of individuals who carry the fragile X mutation. The goal of this 5‐year study is to obtain empiric recurrence risks and population parameters for the fragile X syndrome in order to characterize the underlying mechanism of the mutation and the factors that influence its expression. This report presents the DNA results on the first 152 cases of female carriers and their pregnancy outcomes. It was found that the sex ratio of conceptuses was not significantly different from 1.0 and was not associated with mutation status. Thus, there was no evidence for selection against zygotes with full mutations. There was a significant association between the form of the mutation in carrier mothers and the frequency of its transmission. Examination of the segregation ratios from premutation mothers showed that there was a deficit of conceptuses that received the fragile X mutation. The segregation ratio from full mutation carrier mothers did not differ from expected. Several explanations for this observation are discussed. Numbers of cases are too small to estimate recurrence risks; however, the general trend of the data confirm the association of recurrence risks and the repeat number carried by the mother. © 1994 Wiley‐Liss, Inc.
Asymmetry of methylation with FMR‐1 full mutation in two 45,X/46,XX mosaic females associated with normal intellect
Authors: Shapiro Lawrence R. , Simensen Richard J. , Wilmot Patrick L. , Fisch Gene S. , Vibert Betsy K. , Fenwick Raymond G. , Tarleton Jack , Phelan Mary Catherine 
Published: June 2005

AbstractThe full FMR‐1 mutation is known to cause the fragile X syndrome [Fra(X)], but variable expression in females, including normal to deficient intellect, may be related to random X‐inactivation (lyonization).We have evaluated 2 mosaic 45,X/46,XX females who are cytogenetically fra(X) positive, have an FMR‐1 full mutation, and are of normal intellect. There were 50% fra(X) chromosomes in the 45,X cells of one of the females; this has not been reported previously. In both patients, there was a strong asymmetry of FMR‐1 methylation with the normal allele being totally or 90% unmethylated and the mutant allele being similarly methylated. Thus, the apparent selective inactivation of the full mutant FMR‐1 allele appears to have resulted in limited expression with normal intellect.The presence of the fra(X) chromosome in 45,X cells is unique; however, there may be no relationship to the asymmetric inactivation of the mutant allele which could be due to chance or a mechanism yet to be delineated. © 1994 Wiley‐Liss, Inc.
Unstable triplets and their mutational mechanism: Size reduction of the CGG repeat vs. germline mosaicism in the fragile X syndrome
Authors: Chiurazzi Pietro , Kozak Libor , Neri Giovanni 
Published: June 2005

AbstractThe mechanism responsible for the characteristic expansion of the trinucleotide repeat involved in the pathogenesis of the fragile X syndrome is still largely unclear. Slipped strand mispairing (SSM) and similar DNA replication errors could determine both increases and decreases of the unit number in simple repetitive sequences. Actually, there have been a few reports of size reduction of the (CGG)n in parent‐to‐child transmission of the fragile X syndrome, which may help in understanding the mutational mechanism and may have practical implications for genetic counseling. We describe here 5 such cases from our series of fragile X patients and emphasize the possible role of SSM‐like events in causing (CGG)n expansions and reductions.The possibility that some of these reductions are only apparent, resulting from parental germinal mosaicism is also considered. © 1994 Wiley‐Liss, Inc.
Robust amplification and ethidium‐visible detection of the fragile X syndrome CGG repeat using Pfu polymerase
Authors: Chong Samuel S. , Eichler Evan E. , Nelson David L. , Hughes Mark R. 
Published: June 2005

AbstractWe report on a method for ethidium bromide detection of FMR1 normal and premutation‐size CGG triplet repeats. A set of PCR conditions has been optimized for the polymerase of the hyperthermophilic bacterium, Pyrococcus furiosus. Using this protocol, normal‐size alleles ranging from 5 to 50 repeats, as well as most of premutation‐size alleles, varying from >50 to approximately 200 repeats, could be detected by ethidium bromide staining of agarose gels. Since the protocol requires neither autoradiography nor polyacrylamide gel electrophoresis, it promises to provide a rapid means for the exclusion of fragile X syndrome in males with mental retardation.
Improved sizing of fragile X CCG repeats by nested polymerase chain reaction
Authors: Levinson Gene , Maddalena Anne , Palmer Frances T. , Harton Gary L. , Bick David P. , Howard‐Peebles Patricia N. , Black Susan H. , Schulman Joseph D. 
Published: June 2005

AbstractWe have developed an improved method for polymerase chain reaction (PCR)‐based sizing of the CCG repeat region at the fragile X locus, FMR‐1. This method is designed to optimize denaturation and replication of long repeats with high G + C content, which are otherwise refractory to amplification. The method utilizes nested PCR primers to increase sensitivity and specificity. Alkaline denaturation of the genomic template DNA, combined with addition of glycerol and deaza‐dGTP, facilitates strand separation. Labeled PCR products are sized on denaturing polyacrylamide gels. For alleles in the normal‐to‐premutation size range, strong reproducible signals are routinely obtained from small amounts of rapidly prepared DNA. This allows precise determination of the CCG repeat number, providing data related to the expansion potential of the repetitive segment. Detection of large premutations and some full mutations is also enhanced by the improved procedure. © 1994 Wiley‐Liss, Inc.
X‐linked mental retardation with dystonic movements of the hands (PRTS): Revisited
Authors: Gedeon Agi , Partington Michael , Mulley John 
Published: June 2005

AbstractA family with a syndrome of mental retardation, dystonic movements of the hands, and dysarthria (MIM no. 309510) was described and mapped to Xp22 by Partington et al. (Am J Med Genet 1988; 30:251–262). The original localization encompassed the distal half of the short arm of the X chromosome, with a peak lod score of 2.1 at the DXS41 locus. The gene localization for this disorder (PRTS) has now been refined using recently characterized dinucleotide repeat markers. The PRTS gene maps between DXS365 and DXS28, an interval estimated to be less than 15 cM. A peak lod score of 3.01 at a recombination fraction of zero was generated by 2‐point linkage analysis with the marker DXS989. Dystonic movements may be progressive and could be overlooked in children. Clinical assessments of affected men who are mentally retarded should be critically evaluated for this manifestation, where they belong to families in which the gene localization overlaps with PRTS. © 1994 Wiley‐Liss, Inc.
Regional localisation of a non‐specific X‐linked mental retardation gene (MRX19) to Xp22
Authors: Donnelly Andrew J. , Choo K. H. Andy , Kozman Helen M. , Gedeon Agi K. , Danks David M. , Mulley John C. 
Published: June 2005

AbstractA gene responsible for a non‐specific form of X‐linked mental retardation (MRX19) was localised by linkage analysis. Exclusions and regional localisation were made using 21 highly informative PCR‐based markers along the X chromosome. Significant lod scores at a recombination fraction of zero were detected with the marker loci DXS207, DXS987 (Zmax = 3.58) and DXS999 (Zmax = 3.28) indicating that this gene is localised to the proximal portion of Xp22. Recombination between MRX19 and the flanking loci KAL and DXS989 was observed. The multipoint CEPH background map, with map distances in cM, DXS996‐1.8‐KAL‐19.0‐DXS207‐0.9‐[DXS987, DXS443]‐4.3‐DXS999‐3.5‐DXS365‐14.0‐DXS989. Two other MRX disorders and two syndromal mental retardations, Coffin‐Lowry syndromal and Partington syndrome, have been mapped to this region. There is a possibility that the 3 MRX disorders are the same entity. Most MRX disorders remain clustered around the pericentromeric region. © 1994 Wiley‐Liss, Inc.
New X‐linked mental retardation (XLMR) syndrome with distinct facial appearance and growth retardation
Authors: Brooks Susan Sklower , Wisniewski Krystyna , Brown W. Ted 
Published: June 2005

AbstractWe report on 2 brothers and their nephew with an apparently new X‐linked mental retardation (XLMR) syndrome characterized by a distinct facial appearance, growth retardation, and severe mental retardation. The facial traits included triangular shape; bifrontal narrowness; malar flatness; blepharophimosis; very deeply set eyes; epicanthus inversus; bulbous nose; low hairline; low‐set, deeply cupped, and protruding ears; short ill‐defined philtrum; and thin tented upper lip. These facial anomalies are particularly striking and recognizable even at birth. The boys were small for gestational age and remained below −2 SD in growth parameters. With age, large joint contractures developed. Pectus excavatum was apparent at birth but became more obvious with age. Global developmental delay was evident in infancy. The brothers were nonverbal while their nephew spoke simple words. Optic atrophy, esotropia, nystagmus, and spastic diplegia were evident. They were self‐abusive, hyperactive, and poorly coordinated. CT scans demonstrated atrophic hydrocephalus. No EEG abnormalities were detected. Karyotypes were 46,XY and fragile X negative. Routine chemistries; amino, organic, and uronic acids; oligosaccharides; lysosomal enzymes; and very long chain fatty acids were normal. Remarkable phenotypic similarity between these brothers and their nephew and lack of manifestations in their mothers makes X‐linked recessive inheritance likely. This syndrome, which does not appear to have been reported previously, adds to the delineation of XLMR. © 1994 Wiley‐Liss, Inc.
Is Rett syndrome a chromosome breakage syndrome?
Authors: Telvi Louise , Leboyer Marion , Chiron Catherine , Feingold Josué , Ponsot Gérard 
Published: June 2005

AbstractLymphocytes from venous blood from 15 girls with Rett syndrome (RTS), 7 girls with RTS “forme fruste,” and 46 unrelated control females were examined. All subjects had a normal karyotype using RHG and RTBG technique. The frequency of gaps and breaks was determined for each group. A significantly higher (P < 0.01) frequency of chromosome breakage was observed in RTS subjects compared to controls. This work suggests that an increased tendency to chromosome breakage may be part of a genetically determined disorder in RTS patients. © 1994 Wiley‐Liss, Inc.
Epidemiology of congenital hydrocephalus in Utah, 1940–1979: Report of an iatrogenically related “epidemic”
Authors: Blackburn Brent L. , Fineman Robert M. 
Published: June 2005

AbstractAs part of an epidemiological study of congenital hydrocephalus in Utah, we focused on the effect of ascertainment sources and temporal variability to further delineate the causes of this relatively common, handicapping birth defect. The incidence and distribution of 934 reported cases diagnosed prior to age 6 months, and born to Utah residents from 1940 to 1979, were analyzed. Data were ascertained by examination of multiple sources, e.g., 982,066 birth, 11,161 fetal death, and 248,208 death certificates, and selected hospital and clinic records. Of the 934 reported cases, 700 met our selection criteria for congenital hydrocephalus, which results in a crude incidence of 0.70 per 1,000 live and stillbirths. Seventy‐one cases (10.1%) had additional, multiple congenital anomalies. The male/female sex ratios of the 619 cases of isolated congenital hydrocephalus (occurring as a single entity or in the absence of other reported or known birth defects) and those with multiple congenital anomalies (71 cases) were virtually identical, being 1.45 and 1.48, respectively. A significant 85% increase in the rate of reported cases was observed for the period 1966 to 1970. However, examination of patients' records from 1966 to 1975 in the hospital responsible for almost all of this increase suggests that this was an iatrogenically related “epidemic” caused by several factors: the introduction and possible misinterpretation of pneumoencephalograms (PEG) in the diagnosis of hydrocephalus (PEG was replaced by CAT scanning in the early 1970s), inappropriate diagnosis, and incorrect recording of age at time of diagnosis. © 1994 Wiley‐Liss, Inc.
Preimplantation genetics: A case for prospective action
Authors: Pergament Eugene , Bonnicksen Andrea 
Published: June 2005

AbstractPreimplantation genetics describes a newly‐emerging field in medical genetics, the consequence of the implementation of clinical preimplantation diagnosis and the likely future development of germ‐line gene therapy. Given the existing clinical and laboratory difficulties already demonstrated in preimplantation diagnosis and the sensitive ethical issues surrounding genetic manipulation of human embryos, there is a need for 1) critical and objective evaluation of developments in this field by human and medical geneticists and 2) development of guidelines for research and clinical practice in the years ahead. We propose a course of prospective action for preimplantation genetics implemented through the newly‐formed American College of Medical Genetics in order to address the ethics, safety, accuracy, cost, and overall merit of preimplantation genetics. © 1994 Wiley‐Liss, Inc.
Duplication 10q confirmed by DNA in situ hybridization
Authors: Johnson Virginia P. , Sutliff Willis C. 
Published: June 2005

AbstractPartial duplication of 10q is a recognizable clinical entity. In most of the reported cases, the trisomic segment is identified by a balanced translocation state in a parent. Verification remains a problem in de novo cases. However, the recent availability of whole chromosome probes allows for confirmatory diagnosis of suspected cases. We describe a case of de novo duplication (10q) wiht verification using DNA in situ hybridization. © 1994 Wiley‐Liss, Inc.
Monozygotic twins discordant for gastroschisis: Case report and review of the literature of twins and familial occurrence of gastroschisis
Authors: Bugge Merete , Petersen Michael B. , Christensen M. Fjord 
Published: June 2005

AbstractWe describe a pair of monozygotic (MZ) female twins discordant for gastroschisis. To our knowledge, this is the first such case reported. The zygosity was verified by DNA analysis using highly polymorphic microsatellites. There was no family history of gastroschisis. During pregnancy there was no suspicion of any exposure responsible for the malformation. The number of twin cases described so far does not allow any conclusion as to hereditary factors in the cause of gastroschisis, but the number of families reported with familial gastroschisis suggests that the recurrence risk is higher than previously thought. © 1994 Wiley‐Liss, Inc.
Intermittent hair loss in a child with PIBI(D)S syndrome and trichothiodystrophy with defective DNA repair‐xeroderma pigmentosum group D
Authors: Kleijer Wim J. , Beemer Frits A. , Boom Bart W. 
Published: June 2005

AbstractWe describe a girl with photosensitivity (P), ichthyosis (I), brittle hair (B), impaired intelligence (I), possibly decreased fertility (D), and short stature (S). The clinical findings fit into the PIBI(D)S syndrome and trichothiodystrophy. A remarkable and probably unique observation for this disorder was the intermittent character of the scalp hair loss during infectious periods in this patient.Easy suntanning suggested photosensitivity and prompted DNA repair studies which demonstrated reduced UV‐induced DNA repair synthesis. Subsequent studies have assigned this patient to xeroderma pigmentosum group D and suggested a specific deficiency of 6–4 photoproduct repair. An unaffected child was diagnosed in the next pregnancy of the mother. © 1994 Wiley‐Liss, Inc.
Historical study: Cornelia C. de Lange (1871–1950)—a pioneer in clinical genetics
Authors: de Knecht‐van Eekelen Annemarie , Hennekam Raoul C. M. 
Published: June 2005

AbstractThe life and work in the field of clinical genetics of one of the most outstanding Dutch pediatricians of the first half of the twentieth century, Cornelia C. de Lange (1871–1950), is described against the background of the development of pediatrics, anthropogenetics, and clinical genetics in the Netherlands.Cornelia de Lange specialized in and worked on all aspects of the broad field of pediatrics. During her 50 years of practice she collected an immense series of observations on pediatric disorders. As theories on human genetics developed during the 1920s and 1930s, her interest in congenital disorders and heredity increased as she saw the implications for the pediatric clinic. She benefitted from her vast experience and her knowledge of the national and international literature when she recognised and described new entities, one of which is named after her: the Brachmann‐De Lange syndrome. © 1994 Wiley‐Liss, Inc.
Comparative study of fanconi anemia in children of different ethnic origin in South Africa
Authors: Macdougall Lorna G. , Rosendorff Jennifer , Poole Janet E. , Cohn Richard J. , McElligott Susan E. 
Published: June 2005

AbstractA comparative study of clinical, hematologic, and cytogenetic findings was made in 40 black and 35 white children with Fanconi anemia. The black children were Bantu‐speaking Negroid stock of diverse tribal origin. The white children were predominantly Afrikaans stock of Dutch/German/French Huguenot origin. All of the patients had IFAR scores of 2 to 4+ and over 80% in each group had increased spontaneous and/or mutagen‐induced chromosomal breakage (CB‐positive). There were no significant clinical differences between black and white patients or between CB‐pos and CB‐neg patients, with the exception of white children in whom significantly more CB‐pos patients had thumb and radial anomalies than the CB‐neg patients. The age‐at‐onset of hematologic manifestations was the same for all groups, but more black than white CB‐pos patients were severely anemic at the time of diagnosis.Response to androgen and steroid therapy occurred in only 33% of black children compared with 86–90% of white children; 81% of black patients died during the 18 year study period compared with 30% of white children, but the age at death was similar. More sophisticated studies are required to determine whether these differences are genetically determined or related to cultural, educational, and socio‐economic differences between the two ethnic groups. © 1994 Wiley‐Liss, Inc.