bluuebunny/crossref_metadata_2025_split huggingface dataset:
Pulsed‐field gradient‐gel studies around the fragile site
Authors: Dobkin Carl S. , Brown W. Ted 
Published: June 2005

AbstractUsing pulsed‐field gradient‐gel electrophoresis (PFGE) we compared two fragile X (fra(X)) chromosomes from individuals in families that exhibit linkage heterogeneity between fra(X) and coagulation factor IX (F9). The analysis of very large restriction fragments indicated that there is a structural difference in the interval between fra(X) and F9 near the locus DXS105. Differences were observed in the Sfi I partial digestion analysis and in the Mlu I pattern of the DXS105 region. Digestion with Nru I and Sst II also showed differences between these alleles. The analyses suggest that the alleles differ in a region of >200 kb. Analysis of other normal and fra(X) chromosomes will be necessary to determine whether the observed difference is a normal population variant or if it may be resonsible for the linkage heterogeneity observed between these loci.
Cytogenetic and physical mapping in the region of the X chromosome surrounding the fragile site
Authors: Nguyen Catherine , Mattei Marie‐Geneviève , Rey Juan Antonio , Baeteman Marie‐Antoinette , Mattei Jean‐François , Jordan Bertrand R. 
Published: June 2005

AbstractSeven DNA probes have been mapped within the Xq27‐Xq28 region using in situ hybridization, in some cases on chromosomes expressing the fragile site to enhance the resolution. To complement these studies and investigate the relationship between genetic, cytogenetic and physical distance some of these probes were used for large scale mapping using pulsed field gels. Physical linkage was demonstrated between two loci, F9 and MCF2, which are separated by less than 270 kb, and a restriction map extending over 1,300 kb has been generated.
Investigation of the segregation of the fragile X mutation in daughters of obligate carrier women
Authors: Sherman S. L. , Turner G. , Robinson H. , Laing S. 
Published: June 2005

AbstractTwo reports have suggested that over 50% of the offspring of obligate carrier women receive the mutation for the fra(X) or the Martin‐Bell syndrome [Webb et al, 1986; Fryns, 1984]. Such a segregation distortion is difficult to assess for the fra(X) syndrome because of incomplete penetrance, variable expression and probable ascertainment biases. We have attempted to evaluate this possible segregation distortion in daughters of obligate carriers in a large sample of sibships ascertained in a survey of New South Wales, Australia. We used two definitions of expression: 1) presence of fra(X) positive cells if daughters were tested cytogenetically, and 2) mental impairment if daughters were not tested cytogenetically. The segregation frequency was estimated in different types of sibships of obligate carriers based on the way they were ascertained. This was done in order to have an internal check on possible ascertainment biases. Among the 189 cytogenetically tested daughters, 81 were fra(X) positive. Among the 97 untested daughters, 24 were mentally impaired in some way. Therefore, the segregation frequency as defined by fra(X) expression and/or mental impairment was 37%. Thus, no evidence was detected for segregation distortion. These data were significantly different than those collected by Webb et al {1986} and scored by the same method as the present data set.
Screening developmentally disabled male populations for fragile X: The effect of sample size
Authors: Fisch Gene S. , Cohen Ira L. , Jenkins Edmund C. , Brown W. T. 
Published: June 2005

AbstractThe fra(X) or Martin‐Bell syndrome is the most common cause of inherited mental retardation (MR) in males. It is also associated with a variety of unusual behavioral and developmental disorders. Recent studies found great variability in the estimated strength of association between “autism” and the fra(X) syndrome, but not between MR and fra(X). We examined 31 studies which investigated the association of fra(X) syndrome with either MR or “autism” and found that the conclusions of those researchers could be significantly affected by sample size. Different behavioral and cytogenetic protocols will also influence the strength of association between fra(X) and autism.
Fragile X syndrome: A hypothesis regarding the molecular mechanism of the phenotype
Authors: Warren Stephen T. 
Published: June 2005

AbstractAmong all the human chromosomal fragile sites currently recognized, the fragile site mapping to Xq27.3 is the only one associated with an abnormal phenotype. This phenotype, referred to as the Martin‐Bell or fragile X syndrome, has mental retardation as its most important manifestation. We propose that this site is associated with an abnormal phenotype due its location on the X chromosome, particularly it's proximity to the q telomere. Thus, if an in vivo break should occur with loss of Xq28 in the fra(X) male, the cell would be nullisomic for the genes distal to the fragile site. Similarly, a female cell would be functionally nullisomic if the break occurred on the active X. Breakage and loss of genetic material at other fragile sites either would have no impact due to complementation by homologous genes or would be lethal if X‐linked with a significant deletion (i.e. fra(Xq22)). This leads to the proposal that the fragile X syndrome is due to mosaic nullisomy of distal genes. We describe below the implications of this model and a means to test this hypothesis.
Fragile X expression in Martin‐Bell syndrome, intellectually normal individuals, and neoplasia, interpreted by a viral hypothesis
Authors: Shabtai Fiorella , Hart Jacob , Klar Dvora , Bichacho Shlomo , Halbrecht Isaac 
Published: June 2005

AbstractWe present data on fragile X expression in lymphocytes obtained from the following patients: a university student, an infertile couple, 6 of 22 prostatic cancer patients, a meningioma patient, and members of families with meningioma and familial gliomas. All patients were of normal intelligence. In addition, we report 3 cases of central nervous system (CNS) tumors in more typical fragile X families.We suggest that the fragile X expression as well as the clinical findings may be caused by a viral (or similar) infection. The virus may require a receptor protein coded by one allele of a gene on the X chromosome.
Prenatal diagnosis of deletion 17p13 associated with DiGeorge anomaly
Authors: Greenberg Frank , Courtney Kristine B. , Wessels Robert A. , Huhta James , Carpenter Robert J. , Rich Donna C. , Ledbetter David H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA fetus, subsequently shown to have the deletion 17p13, was detected at 30 weeks' gestation because of multiple anomalies and polyhydramnios on ultrasonography. The fetus died and was born at 34 weeks of gestation. Pathologic examination showed intrauterine growth retardation, double outlet right ventricle (a conotruncal cardiac defect), and thymic hypoplasia suggesting partial DiGeorge anomaly. To our knowledge, DiGeorge anomaly has not been reported previously in conjunction with del(17p) nor in the Miller‐Dieker syndrome. Since this deletion is the largest deletion of distal 17p observed so far, one explanation for this association may be the presence of a gene on proximal 17p for neural crest development.
Sensorineural deafness, hypospadias, and synostosis of metacarpals and metatarsals 4 and 5: A previously apparently undescribed MCA/MR syndrome
Authors: Pfeiffer R. A. , Kapferer L. , Opitz John M. 
Published: June 2005

AbstractWe report on a young man with a syndrome of mental retardation, abnormalities of the brain, sensorineural deafness, hypospadias, bilateral synostosis of the 4th and 5th metacarpals and metatarsals, and abnormal dermatoglyphics. This appears to be a previously undescribed MCA/MR syndrome.
Complex de novo rearrangement involving four chromosomes and ten break points with interstitial deletions and duplication
Authors: Muneer Razia S. , Himes Jeannie , Rennert Owen M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe an unusual de novo case of two interstitial deletions (5q22→5q31; 9p13→9q22) and one duplication (9q22→9q34) resulting from a 10–breakpoint, complex chromosome rearrangement of chromosomes 1, 5, 8, and 9 in a profoundly retarded woman.
Inherited lysosomal storage disease associated with deficiencies of β‐galactosidase and α‐neuraminidase in sheep
Authors: Ahern‐Rindell Amelia J. , Prieur David J. , Murnane Robert D. , Raghavan Srinivasa S. , Daniel Peter F. , McCluer Robert H. , Walkley Steven U. , Parish Steven M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractHistopathologic, ultrastructural and Golgi impregnation studies disclosed lesions characteristic of a neuronal lysosomal storage disease in related sheep with onset of neurologic signs at 4–6 months. Biochemical and enzymatic evaluation disclosed storage of GM1 ganglioside, asialo‐GM1, and neutral long chain oligosaccharides in brain, urinary excretion of neutral long chain oligosaccharides, and deficiencies of lysosomal β‐galactosidase and α‐neuraminidase. Retrospective and limited prospective genetic studies suggested autosomal recessive inheritance. A gene‐dosage effect on β‐galactosidase levels was documented in fibroblasts from putative heterozygous sheep. Fibroblasts from affected sheep did not have increased β‐galactosidase activity after incubation with the protease inhibitor, leupeptin. In some aspects this disease is similar GM1 gangliosidosis, but is unique in that a genetic defect in lysosomal β‐galactosidase may cause the deficiency of lysosomal α‐neuraminidase.
Dandy‐Walker malformation in Ellis‐van Creveld syndrome
Authors: Zangwill Kenneth M. , Boal Danielle K. B. , Ladda Roger L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on 2 Old Order Amish patients with Ellis‐van Creveld (EvC) syndrome and the Dandy‐Walker malformation; a similar case is noted in the literature. Pedigree analysis of our patients documents extensive inbreeding in successive generations. Considering the rarity of EvC syndrome and Dandy‐Walker malformation as isolated malformations, the appearance of both in our 2 patients plus the patient in the literature suggests that Dandy‐Walker malformation may be a manifestation in the EvC syndrome. However, in this isolate the coincidental occurrence of 2 rare recessive traits cannot be excluded.
Probable metachromatic leukodystrophy/pseudodeficiency compound heterozygote at the arylsulfatase A locus with neurological and psychiatric symptomatology
Authors: Hohenschutz Ch. , Friedl W. , Schlör K.‐H. , Waheed A. , Conzelmann E. , Sandhoff K. , Propping P. , Neri Giovanni , Reynolds James F. 
Published: June 2005

AbstractMetachromatic leukodystrophy (MLD) is an autosomal recessive progressive demyelination disorder caused by the deficiency of arylsulfatase A (ASA). However, there exist individuals with low ASA activity without clinical symptoms. This state is described as ASA pseudodeficiency (PD).A number of patients with low ASA activity and various neuropsychiatric symptoms have been observed. It is controversial to what extent low ASA activity predisposes for neurological and/or psychiatric symptomatology. Therefore, persons with low ASA activity who were collected from a large‐scale screening among neuropsychiatric patients and healthy controls are presently being extensively evaluated using biochemical, genetic, and clinical methods. Here we present a female patient, who had been first hospitalized with the diagnosis encephalomyelitis disseminata. Her ASA activity determined in fibroblast extracts is intermediate between adult MLD and PD. Sulfatide degradation in cultured fibroblasts is diminished. The subunit pattern obtained after SDS‐polyacrylamide gel electrophoresis and immunoblotting was determined in the index patient and 2 sibs. It is compatible with a compound genotype ASA−/ASAp in the index case. It appears probable that in this patient low ASA activity leads to the accumulation of sulfatide and either causes the appearance of neuropsychiatric symptoms or at least contributes to the demyelination process.
Juvenile myoclonic epilepsy (JME) may be linked to the BF and HLA loci on human chromosome 6
Authors: Greenberg David A. , Delgado‐Escueta Antonio V. , Widelitz Heidi , Sparkes Robert S. , Treiman Lucy , Maldonado Hector M. , Park Min S. , Terasaki Paul I. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAlthough certain forms of epilepsy have long been suspected to be inherited, heterogeneity has made it difficult to find the genes responsible for any subtypes. We found that families ascertained through patients with juvenile myoclonic epilepsy show linkage with the BF and HLA loci on human chromosome 6. There is some evidence that the locus may be outside the HLA complex and no evidence as yet of an association with any allele of the HLA complex.
The impact of MSAFP screening on genetic services, 1984–1986
Authors: Greenberg Frank , Opitz John M. , Reynolds James F. , Greenberg Frank 
Published: June 2005

AbstractThe impact of maternal serum alpha‐fetoprotein (MSAFP) screening on genetic centers was investigated by a questionnaire mailed to 220 genetic centers in the United States. Eighty‐four (38%) of centers responded to the questionnaire; of these (34%) were adequate for analysis. About 33% of the programs performed their own MSAFP testing. Approximately 70% of centers used 2.5 times the median (MoM) as a cutoff for MSAFP elevations and approximately 75% of centers used a sliding cutoff for low MSAFP based on both maternal age and the multiple of the median.Between 1984 and 1986, the total number of women screened by the reporting centers increased by about 4.7 fold. The percentage of women seen in their centers for prenatal counseling due to high or low MSAFP levels increased from 1.3% in 1984 to 13.1% in 1986.The percentage of prenatal diagnoses utilizing amniocentesis for high or low MSAFP increased from 3% in 1984 to 10% in 1986.During this period, 76 cases of Down syndrome were detected based on low MSAFP; this represents 1.7% of amniocenteses for low MSAFP.These data demonstrate a significant increase in the number of women seen for prenatal counseling and amniocentesis at the reporting genetic centers and is likely to represent a similar trend at all genetic centers. The impact of high MSAFP screeing for neural tube defects and low MSAFP screening for Down syndrome is likely to increase over the coming years and genetic programs should prepare for the increasing utilization of services necessary to handle women with high and low MSAFP levels.
Assessment of reproductive risk and intentions by mothers of children with hemophilia
Authors: Kraus Elissa M. , Brettler Doreen B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThirty‐five mothers of children with hemophilia were studied in order to ascertain the impact of hemophilia on family planning. Attitudes about reproductive risks and prenatal diagnosis were also examined. The most important factors influencing family planning in this group were parental fulfillment and availability of medical care and education for their affected child. Although 79% of mothers viewed their reproductive risk as moderate to very high, 57% indicated that their reproductive plans had not changed even with this knowledge. While 43% of the group would consider prenatal diagnosis, only 17% would terminate a pregnancy if the fetus was found to have hemophilia. Of those interested in prenatal diagnosis, the majority were interested in knowing if the fetus was affected but would not consider termination of the pregnancy. The majority of mothers in the group did not view having a child with hemophilia as an insurmountable burden on their lives. Therefore, the disease appeared to have little impact on family planning.
Genetic and environmental components of serum creatine kinase (CK) and pyruvate kinase (PK) in normal twins: Implication for genetic risks estimates in Duchenne muscular dystrophy carriers
Authors: Rapaport Debora , Colletto Gloria M. D. D. , Zatz Mayana , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe serum activity of creatine kinase (CK) and pyruvate kinase (PK) was measured in 98 pairs of same‐sex Brazilian twins. The purpose of this study was to estimate the genetic and environmental components of serum activity levels for both enzymes. Heritabilities were estimated separately by path analysis in each sex. The results showed that CK and PK activities are under genetic control in normal males and females. Environmental components were not statistically significant for CK or PK. The genetic components of both enzymes estimated in females has implications in the calculation of genetic risks for Duchenne muscular dystrophy carriers.
Lid agenesis‐macrostomia‐psychomotor retardation‐forehead hypertrichosis—A new syndrome?
Authors: Cesarino E. J. , Pinheiro Marta , Freire‐Maia Newton , Meira‐Silva M. C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe a boy with bilateral lid agenesis and total keratinization of cornea and conjunctiva, macrostomia, psychomotor retardation, forehead hypertrichosis, ocular hypertelorism, thin lips, abnormal auricles and nose, skin alterations, and other findings. Differential diagnosis with ablepharon‐macrostomia syndrome is presented. Cause is unknown.
Selective termination of multiple gestations
Authors: Golbus Mitchell S. , Cunningham Nona , Goldberg James D. , Anderson Robert , Filly Roy , Callen Peter , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractTwenty‐two selective terminations in multiple gestations were performed by a number of different methods. In 17 dichorionic pregnancies there was a successful delivery in surviving singletons or twins. In five monochorionic pregnancies undergoing selective termination there was a successful delivery in only one and a pregnancy loss in the other four. Six of the 18 delivered pregnancies were complicated by premature labor and delivery. Among the several methods used for selective termination, intracardiac potassium chloride injection appears to be the procedure of choice in dichorionic pregnancies.
Fechtner syndrome: Clinical and genetic aspects
Authors: Gershoni‐Baruch R. , Baruch Y. , Viener A. , Lichtig C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFechtner syndrome, a variant of Alport syndrome, was first reported by Peterson et al. [1985]. It is characterized by nephritis, hearing loss, eye abnormalities, macrothrombocytopenia, and leucocyte inclusions, present in varying combinations in several members of the same family. This is the second family reported; 16 relatives are affected. The clinical manifestations of the syndrome are delineated. The pattern of inheritance is autosomal dominant. The hematologic abnormalities are similar to those detected in May Hegglin anomaly. They are present in every affected relative and may be present at birth. The feasibility of prenatal diagnosis is discussed.
Preliminary communication: Neuroanatomical variations of the posterior fossa in men with the fragile X (Martin‐Bell) syndrome
Authors: Reiss Allan L. , Patel Shilpesh , Kumar Ashok J. , Freund Lisa , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFour men with fragile X (fra (X)), or Martin‐Bell, syndrome were studied by magnetic resonance imaging (MRI) to determine whether detectable abnormalities of the cerebellum were present. The cerebellum was chosen because of the apparently increased tendency for fra (X) patients to demonstrate autistic behavior and accumulating evidence implicating cerebellar abnormalities in autism. Compared with a control group of four normal men, fra (X) patients had a significantly decreased area of the cerebellar vermis, particularly the posterior portion, on planimetric analysis in the midsagittal plane. The pons and fourth ventricular areas also were decreased and increased, respectively, in the fra (X) men. Neuroanatomical and animal research increasingly implicates the cerebellar vermis as an important component in functional brain systems subserving sensory and motor integration, learning, and modulation of affect, motivation, and social behavior. Thus, vermis dysfunction could account for many of the behavioral and cognitive abnormalities observed in fra (X) males, particularly those which overlap with the behavioral syndrome of autism.
Complex chromosomal rearrangement in a woman with multiple miscarriages
Authors: Kausch Katrin , Haaf Thomas , Köhler Julia , Schmid Michael , Neri Giovanni , Reynolds James F. 
Published: June 2005

AbstractWe report on a 23‐yr‐old healthy female with repeated miscarriages and a de novo complex chromosomal rearrangement (CCR) involving chromosomes 1, 2, 5 and 11 with 5 breakpoints. A review of cases reported in the last five yr is provided.
Idiopathic extrahepatic biliary atresia: Recurrence in sibs in two families
Authors: Cunningham Michael L. , Sybert Virginia P. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSince 1855, 11 instances of familial extrahepatic biliary atresia (EHBA) have been described. Genetic, environmental, vascular, and infectious causes for this disorder have been proposed. We report on 2 families each with 2 sibs with EHBA. We suggest that a genetic susceptibility to an environmental insult to the biliary tree may be responsible for the genesis of this disease.
Martin‐Bell syndrome in Greece, with report of another 47,XXY fragile X patient
Authors: Mavrou Ariadni , Syrrou Maria , Tsenghi Christine , Agelakis Manthos , Youroukos Sotiris , Metaxotou Catherine , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA cytogenetic investigation was carried out among 200 mentally retarded boys in Greece for the detection of the fragile X [fra(X)] syndrome. Thirteen patients were found to carry fra(X) (6.5%). Of those, six boys had a history of familial X‐linked mental retardation, two had the phenotype of the Martin‐Bell syndrome, four had only mental retardation of unknown etiology, and one was a mentally retarded patient with Klinefelter syndrome. The remaining 187 boys were fra(X) negative. Our findings emphasize the importance of early identification of this syndrome in the diagnosis and prevention, through proper genetic counselling, of mental retardation.
Metacarpophalangeal pattern profile analysis in fragile X syndrome
Authors: Butler Merlin G. , Fletcher Mark , Gale David D. , Meaney F. John , McLeod D. Ross , Fagan Joel , Carpenter Nancy J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe analyzed the metacarpophalangeal pattern profile (MCPP) on 18 male individuals from 16 families with fragile X—fra (X), or Martin‐Bell—syndrome and calculated a mean syndrome profile. Fourteen of 18 individuals with fra (X) syndrome had significant positive correlations which indicated clinical homogeneity. Discriminant analysis of individuals with fra (X) syndrome compared with a sample of normal individuals produced a correct classification rate of 88% based on a function of 3 MCPP variables that may provide a useful tool in screening individuals for the fra (X) syndrome. Discriminant and correlation analyses of individuals with Sotos sequence and individuals with fra (X) syndrome did not identify MCPP similarities. Therefore, there was no MCPP evidence in our study of patients with Sotos sequence and fra (X) chromosome expression.
Balanced X;15 translocation 46,X,t(X;15)(q21;q23) associated with primary amenorrhea
Authors: Ji Xue‐Wen , Chen Xiao‐Yi , Tan Jun , Liang Hong , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractCytogenetic studies on a woman with primary amenorrhea showed an X;15 translocation, karyotype 46,X,t(X;15)(q21;q23). Fifteen percent of the buccal cells showed a normal‐sized sex chromatin body. The normal X chromosome was uniformly inactivated. Many balanced X;15 translocations have been reported; however, breakpoints in our patient differ from those reported previously. This case also supports earlier evidence that ovarian development fails when the breakpoint of the X chromosome is in the region X q13‐q25 or q13‐q27.