bluuebunny/crossref_metadata_2025_split huggingface dataset:
A new family with fra(10)(q25): Spontaneous expression and 100% expression with 100 μM BrdU
Authors: Gollin Susanne M. , Bock Hans‐Georg O. , Caskey C. Thomas , Ledbetter David H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a family with fra(10)(q25) ascertained through a female with multiple minor anomalies and present in her phenotypically normal father and other family members. The site is expressed spontaneously at levels of 9% in lymphocytes, 2% in lymphoblasts, and 6% in skin fibroblasts. Expression frequency is significantly enhanced to levels as high as 100% by addition of BrdU to the culture medium. The consistently high level of induced expression in lymphoblasts from the proband facilitates analysis of the biochemical and structural bases of fragile site expression.
The Pena‐Shokeir syndrome: Report of nine Dutch cases
Authors: Lindhout D. , Hageman G. , Beemer F. A. , Ippel P. F. , Breslau‐Siderius L. , Willemse J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on nine individuals with the Pena‐Shokeir syndrome. Clinical findings are compared with data on patients from the literature. Emphasis is made on genetic background, neuropathological findings, and (in two cases) on prenatal data. Possible pathogenetic mechanisms are discussed.
Antifolate‐induced misincorporation of deoxyuridine monophosphate into DNA by cells from patients with the fragile X syndrome
Authors: Wang Jin‐Chen C. , Beardsley G. Peter , Erbe Richard W. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe fragile site at Xq27 is expressed in vitro under conditions that lead to decreased intracellular thymidine triphosphate concentration, a condition which has also been shown to promote the misincorporation into DNA of deoxyuridine monophosphate (dUMP) in place of thymidine. We tested for increased whole‐cell misincorporation of dUMP as a possible molecular mechanism for the expression of the fragile X abnormality. Neither deoxyuridine triphosphatase nor uracil‐DNA‐glycosylase, the two enzymes that normally prevent the accumulation of dUMP in DNA, was deficient in fragile X syndrome cells. Misincorporation of dUMP occurred in comparably low levels in both normal and fragile X syndrome lymphoblasts. Although these results provide strong evidence against generalized misincorporation of dUMP in fragile X syndrome cells, a substantial real difference present at Xq27 might not be detected in these studies of whole cells containing the diploid chromosome complement.
A premutation that generates a defect at crossing over explains the inheritance of fragile X mental retardation
Authors: Pembrey M. E. , Winter R. M. , Davies K. E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe view that the Martin‐Bell syndrome (X‐linked mental retardation with fragile site at Xq27/8) is inherited in a regular X‐linked fashion is becoming untenable with the increasing number of reports of transmission through phenotypically normal males. Analysis of the published pedigrees containing such males shows that their heterozygous daughters are never mentally retarded, and have either no fragile site or very few indeed. By contrast, in the next generation, a third of the female heterozygotes are mentally subnormal with an average of 29% fragile sites. These data suggest a premutation that generates the definitive mutation only when transmitted by a female. We propose an inherited sub‐microscopic chromosome rearrangement involving the Xq27/8 region that causes no ill effect per se, but generates a significant genetic imbalance when involved in a recombination event with the other X chromosome. This hypothesis explains many of the puzzling genetic aspects of the Martin‐Bell syndrome, but it also complicates the interpretation of linkage analysis with genetic markers.
Vascular abnormalities in a fetus with multiple pterygia
Authors: Fitch Naomi , Rochon Louise , Srolovitz Herbert , Hamilton Emily , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe a 16‐week fetus with a lethal multiple pterygium syndrome and hydrops. No bony abnormalities were noted on radiographic or anatomical examination. A prominent meshwork of dilated, thin‐walled vessels was present in the subcutis over the entire body. This abnormal vascularity may have caused pterygium formation and death of the fetus.
The inheritance of spontaneous amyloidosis development in mice: A model for hereditary threshold metabolic disorders
Authors: Chai C. K. , Lerner Charles , Prieur David J. 
Published: June 2005

AbstractTo study the inheritance of spontaneous amyloidosis development in mice, we crossed the LLC strain (with a high incidence) with the A/J strain (with a low incidence) and with the HLC strain (with a zero incidence of amyloidosis). We produced the F1 and a backcross generation to each parental strain in each cross. Examination of the spleen, liver, and kidneys of each mouse for the presence of amyloid was made between age 15 and 18 months. The data fit neither a dominant nor a recessive single gene hypothesis for the development of amyloidosis. In consideration of amyloidosis as a hereditary threshold character, we developed an additive gene model. Subsequently, a test for fitness of the observed percentages to the expected percentages in the backcross generations was made according to this model. The observed percentages of amyloidosis in the spleens, livers, and individual mice agreed with the expected percentages in the LLC × A/J crosses but not in the LLC × HLC crosses. Therefore, we conclude that for the development of amyloidosis, a difference exists at one locus between LLC and A/J and at more than one locus between LLC and HLC. The probability of development of amyloidosis in an individual depends on the effects of the genes at these loci. For hereditary metabolic disorders that cannot be explained by either a single dominant or recessive gene hypothesis, this genetic model may be useful to test whether the development of the disease is due to additive effects of genes.
Deficiency of chromosome 8p21.1→8pter: Case report and review of the literature
Authors: Dobyns William B. , Dewald Gordon W. , Carlson Richard O. , Mair Douglas D. , Michels Virginia V. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe clinical manifestations and cytogenetic changes of a patient with 46,XY,del(8)(p21.1) are compared with those of nine other patients with a similar deficiency of chromosome 8. Patients with this chromosome anomaly have a syndrome of postnatal growth retardation, microcephaly, mental retardation, epicanthal folds, posteriorly angulated and malformed ears, short neck, relatively increased internipple distance, and congenital heart defect. A short and broad nose, a wide and flat nasal bridge, and a small jaw are observed in young patients but tend to become less apparent with increasing age. In most instances, the syndrome has been associated with a de novo chromosome abnormality. Levels of glutathione reductase in our patient were normal—a finding consistent with localization of the gene coding for this enzyme to the proximal part of band 8p21.1 if gene dosage studies are reliable.
Facioscapulohumeral dystrophy with cochlear hearing loss and tortuosity of retinal vessels
Authors: Gieron Maria A. , Korthals Jan K. , Kousseff Boris G. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a mother and her three children with facioscapulohumeral dystrophy (FSHD), sensorineural hearing loss, and marked tortuosity of the retinal vessels. Initially the children presented with speech difficulties and hearing deficit. Hearing loss ranged from mild to severe. An audiologic evaluation, including brain stem auditory evoked responses in all patients, indicated a cochlear origin of hearing loss and intact pathways from the cochlea to the temporal lobe. The association of FSHD with hearing loss and tortuosity of the retinal vessels suggests previously unrecognized pleiotropy of FSHD (McKusick 15890) or a “new” type of FSHD.
Muscular dystrophy in Saskatchewan Hutterites
Authors: Shokeir M. H. K. , Rozdilsky B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA slowly progressive form of muscular dystrophy was studied in a Dariusleut Hutterite kindred from a colony in west‐central Saskatchewan. The disorder combines some characteristics of the dominantly inherited facio‐scapulo‐humeral and the recessively inherited limb‐girdle types of muscular dystrophy. Intellect, vision, hearing, and sensations were normally preserved. Nerve conduction was also intact.The disorder reported herein resembles a type of muscular dystrophy we previously described in the Manitoba Schmiedeleut Hutterites [Shokeir and Kobrinsky, 1976]. This condition, which affects both sexes, appears to be genetic in origin and recessively inhertited.
Neurofibromatosis and fragile‐X syndrome in the same patient
Authors: Mitchell Joyce A. , Wray Jane , Michalski Karen , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on an 11 1/2‐year‐old boy with neurofibromatosis and the fragile‐X syndrome. Clinical manifestation of neurofibromatosis included multiple cafe‐au‐lait spots, axillary freckles, congenital glaucoma, relative macrocephaly, radiologic findings of overtubulation of the long bones, and precocious puberty. The fragile‐X syndrome manifests itself as mental retardation with behavior problems, macroorchidism, and specific cytogenetic findings. The boy has normal serum hormone levels, but a greatly elevated FSH on a first morning void, which contains the nocturnally secreted gonadotropins.This seems to be the first reported occurrence of the fragile‐X syndrome with another inherited disease.
Translocation mosaicism in a woman having multiple miscarriages
Authors: Sciorra Leonard J. , Lee Ming‐Liang , Cuccurullo Gail , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe concluded cytogenetic studies on a couple who had had several spontaneous abortions. The peripheral lymphocytes of the woman repeatedly showed a mosaic pattern with a structurally altered, apparently balanced, autosomal translocation between chromosomes 4 and 5. Various studies were reviewed and it was concluded that the true frequency of structural rearranged mosaics in recurrent pregnancy loss is not known.
A family with the Saethre‐Chotzen syndrome
Authors: Bianchi Elena , Aricǒ Maurizio , Podestǎ Alberto F. , Grana Marco , Fiori Paola , Beluffi Giampiero , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAcrocephalosyndactyly (ACS) is an inherited syndrome of premature synostosis of the cranial sutures and abnormalities in the distal segments of the limbs. Several forms of ACS have been described. ACS type III (or Saethre‐Chotzen syndrome) is characterized by microcephaly, skull asymmetry, mild syndactyly, and facial abnormalities. We describe an Italian family with ACS III in which two sibs are clearly affected; the mother and the maternal grandmother show some features of the syndrome.
The prenatal detection of the fragile X chromosome: Review of recent experience
Authors: Jenkins Edmund C. , Brown W. Ted , Wilson Miriam G. , Lin Ming S. , Alfi Omar S. , Wassman E. Robert , Brooks Judith , Duncan Charlotte J. , Masia Annette , Krawczun Michael S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe fragile X chromosome has been identified in specimens from 17 male and 10 female fetuses in 11 laboratories throughout the world, obtained from at least 79 fetuses at increased risk for the fra(X) syndrome. Of these, 19 were confirmed, 6 were pending, 1 was negative and 1 could not be confirmed. Twenty‐five of the 79 cases were studied in our laboratory (Institute for Basic Research [IBR]) and resulted in fra(X) demonstration in specimens from 3 male and 5 female fetuses. All 3 males and 2 of the 5 females have been confirmed. When aniocytes from a the two confirmed female fetuses were exposed to FUdR after culturing in Chang medium, fra(X) frequencies were virtually negative indicating that Chang medium should not be used in fragile X studies at least when FUdR is used to induce fragility. Finally, amniocytes from a fra(X) male fetus studied in 3 different laboratories exhibited strikingly different frequencies. To date, we have experienced no falsepositives or negatives, but the latter case was controversial. It is recommended that laboratories undertaking fra(X) prenatal detection use a combination of at least two different proven induction systems as well as complementary DNA marker studies to prevent false negative diagnosis.
Fragile X and autism: A multicenter survey
Authors: Brown W. Ted , Jenkins Edmund C. , Cohen Ira L. , Fisch Gene S. , Wolf‐Schein Enid G. , Gross Anne , Waterhouse Lynn , Fein Debra , Mason‐Brothers Ann , Ritvo Edward , Ruttenberg Bertram A. , Bentley William , Castells Salvador , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe screented 183 autistic males for the fra(X) and found 24 (13.1%) to be positive. Adding the subjects of this study to those of 11 other surveys, of which 6 were positive and 5 were negative, a total of 614 autistis males have been screened. Overall 47 (7.7%) were positive. Based on this estimate and the prevalence of autism and fra(X), we estimate that 12.3% of fra(X) males are autistic. We have found that 17.3% of our fra(X) males were autistic and overall a 21.2% frequency has been reported, these higher figures are most likely due to biases in age and ascertainment. With an overall 7.7% frequency of fra(X) among autistic males and an estimated 12.3% of autism among fra(X) males, we conclude there is likely to be a significant association of fra(X) with autism. Because fra(X) appears to be the single most common cause of the condition, chromosomal testing is recommended for any autistic person with undiagnosed etiology.
Infantile autism: An occasional manifestation of fragile (X) mental retardation
Authors: McGillivray Barbara C. , Herbst Diana S. , Dill Frederick J. , Sandercock H. Joyce , Tischler Bluma , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractClassical infantile autism occurs more frequently in males and has recently been noted in patients with the fragile (X) form of X‐linked mental retardation (XLMR). In order to better understand this association and to determine whether fra(X) XLMR could account for the excess of autistic males, we investigated a group of institutionalized severely handicapped adults, 33 males and eight females, who were diagnosed as autistic using the DSM III diagnostic criteria of infantile autism. Chromosome studies using FUdR showed that three of the males had the Xq27 fragile site. We confirmed the association of autism and fra(X) XLMR, and showed that this extreme form of behaviour is part of the spectrum seen in the Martin‐Bell syndrome. Two of the three autistic males with the Xq27 fragile site had ahistory of birth insults, which in combination with developmental deficits due to the fragile X gene, might have led to the behavioural disorder. Even though the fragile X cannot account for the excess of males with classical autism, it is an important X‐linked factor in its cause. The diagnosis can allow more accurate counselling for this subset of autistic males.
Autism in fragile X females
Authors: Hagerman Randi J. , Chudley Albert E. , Knoll Joan H. , Jackson Alfred W. , Kemper Melinda , Ahmad Razia , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe present two women with the fragile X syndrome (Martin‐Bell syndrome) and autism. Both are mentally retarded, one mildly and one severely. Cytogenetic studies showed a high percentage of lymphocytes with the fragile X chromosome and inactivation occurring preferentially in the normal X chromosome.Autism is shown to be a severe behavioral and cognitive manifestation of the fragile X syndrome in females.
Fra(2) (q13) and inv(9) (pllq12) in autism: Causal relationship?
Authors: Jayakar Parul , Chudley Albert E. , Ray Mano , Evans Jane A. , Perlov Jack , Wand Rox , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractTwenty individuals with autism or related disorders underwent chromosome analysis and physical examinations with documentation of minor anomalies. Chromosome anomalies were identified in 3: 2 had the heritable folate sensitive fra (2) (q13) site and 1 had an inv (9) (p11q12). No heritable chromosome variants or anomalies were seen in 20 age and sex‐matched control individuals. When patients with the fra (2) were excluded from analyses, there was no difference in the frequency of chromosome breaks and/or gaps between the study group and control group. The results of this study suggest that heritable folate sensitive fragile sites and other chromosome variants may be more commonly seen in individuals with autism or related disorders in childhood than in the general population.
Psychiatric disability associated with the fragile X chromosome
Authors: Reiss A. L. , Feinstein C. , Goldsmith K. E. Toomey B. , Rosenbaum K. , Caruso M. A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFragile X (or Martin‐Bell) syndrome, a common, genetic, mental retardation disorder is increasingly being recognized as a major cause of cognitive disability and psychiatric illness in boys. Here, we present a study in which relatives in 4 generations of a large family with the fra(X) chromosome were given comprehensive psychiatric evaluations in order to further describe the psychopathology associated with this condition. Three of 4 males with the fra(X) chromosome were found to have autistic behavior. An adult fra(X) male had a chronic schizoaffective disorder and mental retardation. In femal relatives, a relationship was found between the fra(X) carrier status and psychopathology including schizoaffective and major affective disorders.
The fragile(X) syndrome: The mutation problem
Authors: Jacobs Patricia A. , Sherman Stephanie , Turner Gillian , Webb Tessa , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn an attempt to understand the nature of the mutational event leading to the fra(X) syndrome, we have searched for sporadic cases in 3 populations: affected males, affected females, and non‐affected transmitting females. In all 3 populations there was a dearth of isolated cases, and the reasons for this are discussed.
Trisomy 22 mosaicism syndrome and Ullrich‐Turner stigmata
Authors: Wertelecki W. , Breg W. R. , Graham J. M. , Iinuma K. , Puck S. M. , Sergovich F. R. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractMosaic trisomy 22, ascertained in three unrelated patients, was found to be associated with body asymmetry and signs of the Ullrich‐Turner syndrome including short stature, ptosis, webbed neck, nevi, cubitus valgus, dysplastic nails, malformed greatvessels, and abnormal ovaries. These anomalies in trisomy 22 mosaicism have not been emphasized heretofore. In each of our patients, trisomy 22 mosaicism was found only in fibroblasts. In one patient, the trisomy resulted from a paternal first meiotic nondisjunction, and in the 46,XX cells, both chromosomes 22 were of paternal origin.
A new skeletal dysplasia syndrome with dwarfism, craniofacial anomalies, and unique radiographic findings
Authors: Jones Kenneth Lee , Jones Kenneth Lyons , Miller Kenneth , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a boy from a consanguinous marriage who has a unique skeletal dysplasia, marked dwarfism, mild developmental delay, eye abnormalities, and cranofacial and skeletal changes that have not been described previously.
Three new cases of Tel Hashomer camptodactyly syndrome in one Arabic family
Authors: Tylki‐Szymanska Anna , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThree new cases with the Tel Hashomer camptodactyly syndrome have been ascertained in an Arabic family. This report emphasizes some of the manifestations seen in these three relatives. The Tel Hashomer captodactyly syndrome is thought to be a connective tissue disorder of unknown basic defect.
A balanced de novo X/autosome translocation in a girl with manifestations of lowe syndrome
Authors: Hodgson S. V. , Heckmatt J. Z. , Hughes E. , Crolla J. A. , Dubowitz V. , Bobrow M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe Oculo‐cerebro‐renal syndrome of Lowe is an X‐linked recessive disorder characterised by mental and growth retardation, renal rickets with renal tubular acidosis, generalised aminoaciduria, hypotonia, cataracts, glaucoma and frontal bossing. Manifestations of this syndrome were seen in a girl with no family history of the disorder, but who was found to have a de novo balanced X/3 translocation, with a breakpoint at Xq25. She had also inherited a balanced 14/17 translocation from her father. It is postulated that the clinical picture may be the result of disruption of the X chromosome within the gene at the locus for Lowe syndrome, with non‐random inactivation of the normal X, which may permit the expression of this X‐linked recessive disorder in a girl.
Growth hormone deficiency in the Rothmund‐Thomson syndrome
Authors: Kaufmann Silvia , Jones Marilyn , Culler Floyd L. , Jones Kenneth Lee , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe the first proven occurrence of growth hormone deficiency in an individual with the Rothmund‐Thomson syndrome. This was suspected because of the patient's severely retarded growth and bone age and her failure to respond normally to growth hormone stimulation testing with I‐DOPA, arginine, and growth hormone releasing factor. In addition, we have briefly reviewed other genetic and malformation syndromes that have been found associated with growth hormone deficiency. We recommend that growth hormone deficiency be considered in these syndromes, especially when the growth failure is more marked than expected.
The Perlman familial nephroblastomatosis syndrome
Authors: Greenberg Frank , Stein Fernando , Gresik Mary V. , Finegold Milton J. , Carpenter Robert J. , Riccardi Vincent M. , Beaudet Arthur L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractIn 1973, Perlman et al described a familial syndrome of bilateral renal hamartomas with or without nephroblastomatosis, macrosomia, islet cell hypertrophy, unusual facies, and early lethality. Two additional sibs were recently reported by Neri et al [1984]. We report on two sibs with polyhydramnios, fetal ascites, and abdominal muscular hypoplasia, visceromegaly, and subsequent development of Wilms tumor in one of them. Delineated features of this syndrome include visceromegaly, macrosomia, renal hamartomas, nephroblastomatosis, cryptorchidism in males, unusual facial appearance, polyhydramnios, fetal ascites, and Wilms tumor but do not include hemihypertrophy, omphalocele or umbilical abnormalities, aniridia, or other conditions known to be associated with wilms tumor. This condition should be considered primarily in the differential diagnosis of fetal ascites without hydrops and possibly in the differential diagnosis of familial Wilms tumor, polyhydramnios, congenital hepatomegaly, or nephromegaly.
A new syndrome of severe upper limb hypoplasia and Müllerian duct anomalies
Authors: Halal Fahed , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on the occurrence of a new syndrome of upper limb hypoplasia and Müllerian duct anomalies in a French Canadian family. Limb/acral anomalies varied in expression from postaxial polydactyly to ectrodactyly to severe upper limb hypoplasia with split hand. Genital anomalies varied in expression from only a vaginal septum to complete duplication of uterus and vagina in the female to a micropenis in one of two affected males. The syndrome appears to be inherited as an autosomal dominant trait.