bluuebunny/crossref_metadata_2025_split huggingface dataset:
Screening for methylmalonic aciduria in alberta: A voluntary program with particular significance for the Hutterite Brethren
Authors: Fowlow S. Beatrice , Snyder Floyd F. , Holmes T. Mary , Morgan Kenneth , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA selective, voluntary urine screening program has been established to facilitate detection and early treatment of infants with methylmalonic acidurias (MMA), a group of rare, potentially lethal, autosomal recessive disorders of organic acid metabolism. The laboratory methods have been modified for newborn infants so that urine specimens can be collected on filter paper in the diaper and tested by the thin‐layer chromatography method. One Hutterite child was previously known to have methylmalonyl‐coenzyme A (MMCoA) mutase deficiency (mut0) which is unresponsive to vitamin B12 but is responsive to diet and other therapeutic measures. No undiagnosed existing cases of MMA were identified by the voluntary screening program among 1,165 Hutterite infants and preschool children.
Disequilibrium syndrome in montana hutterites
Authors: Pallister Philip D. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis is a preliminary note on the occurrence of the disequilibrium syndrome (DES) in the Dariusleut Hutterites of Montana. Previously the condition was reported in the Dariusleut of Alberta by Schurig et al [1981] as an automosal recessive, non‐progressive neurological disorder with congenital hypotonia, considerable psychomotor retardation, unsteady broadly based gait and stance, increased deep tendon reflexes, and mild to moderate mental retardation. Affected individuals were short. In the Montana family studied by us in 1981, a brother and three sisters are affected.
NOR activity and centromere suppression related in a de novo fusion tdic(9;13)(p22;p13) chromosome in a child with del(9p) syndrome
Authors: Daniel Art , Ekblom Linda , Phillips Sandra , Fitzgerald Joan M. , Opitz John M. , Riccardi Vincent M. 
Published: June 2005

AbstractA female infant with del(9p) syndrome was found to have the karyotype 45,XX,tdic(9;13)(p22;p13) de novo. In the translocation chromosome, various combinations of AgNOR activity and inactivity were found with suppression of either the 9 or neither centromere. These phenomena of discontinuous centromeric suppression and variation in NOR activity in the one chromosome were scored on AgNOR, GTG, and a combination of AgNOR‐ and GTG‐banded preparations. With AgNOR staining, 15.8% tdic chromosomes were AgNOR‐positive, and this coincided (in preparations with GTG banding only) with 16% tdic chromosomes with a nonstaining gap present at the NOR site. This suggested that when the NOR‐nonstaining gap was present the AgNOR staining would be positive; this was confirmed by the absence of gaps in combination AgNOR–GTG‐banded preparations. In cells with tdic–NOR‐negative chromosomes, equal proportions of cells with the 13 or both centromeres constricted were observed, but in cells with tdic‐AgNOR‐positive chromosomes there was only half the proportion of tdic chromosomes with both centromeres constricted; ie, there was a (significant) tendency towards inactivity of the NOR when both centromeres were constricted in the tdic chromosome. Therefore, the 2 phenomena, variation in NOR activity and centromeric suppression, are interrelated in this case.
Microcephaly, hypergonadotropic hypogonadism, short stature, and minor anomalies: A new syndrome
Authors: Mikati Mohamad A. , Najjar Samir S. , Sahli Itaf F. , Mansour Sylvie , Der Kaloustian Vazken M. , Melhem Rafik E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFour sibs, three males and one female, had microcephaly, hypergonadotropic hypogonadism, short stature, and multiple congenital anomalies. They had five normal sibs and consanguineous parents. Findings in the affected sibs also included a narrow forehead, synophrys, micrognathia, abnormally folded pinnae, early loss of teeth in three, cubitus valgus in two, genu valgum, gynecomastia, and undescended testes in one. All sibs had normal chromosomes. Results of tests for growth hormone release and adrenocortical function were normal. Luteinizing hormone releasing hormone (LHRH) and human chorionic gonadotropin (hCG) stimulation tests were consistent with primary gonadal failure. Testicular biopsy, performed on two affected males, was normal in one and showed focal atrophy with decreased spermatogenesis in the other. The patients manifest a phenotype different from all other known types of hypergonadotropic hypogonadism and appear to represent a new MCA/MR syndrome.
Gingival fibromatosis with sensorineural hearing loss: An autosomal dominant trait
Authors: Hartsfield James K. , Bixler David , Hazen Raymond H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractGingival fibromatosis is a heterogeneous entity that can occur both as a part of syndromes and as an isolated trait. We describe the second family with a rare, dominantly inherited syndrome of gingival fibromatosis and progressive sensorineural hearing loss.
Phenotypic variation in the del(12p) syndrome
Authors: Kivlin Jane D. , Fineman Robert M. , Williams Marc S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractPrevious reports suggested the existence of a del(12p) syndrome. Phenotypic abnormalities associated with del(12p) appear to be mental retardation, microcephaly, and micrognathia. The patient with del(12p) reported here was normocephalic and large for gestational age. She probably had sclerocornea, a finding not previously associated with del(12p). Phenotypic variation in del(12p) syndrome is probably caused by differences in the size of the deleted segment and/or the presence or absence of mutant genes on the homologous 12p segment.
Prenatal diagnosis of neuronal ceroid‐lipofuscinoses
Authors: Macleod Patrick M. , Dolman Clarissa L. , Nickel Robert E. , Chang Eva , Nag Sukriti , Zonana Johnathan , Silvey Kerry , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on the successful prenatal diagnosis of the late infantile “Jansky‐Bielschowsky” variant of the neuronal ceroid‐lipofuscinoses (NCL). The fetus was studied at 16 weeks of gestation because of an affected sib. Uncultured amniotic fluid cells were studied by conventional electron microscopic techniques. About one‐third of a subpopulation of dark, elongated cells contained one or more deposits of curvilinear cytosomes bound by a single unit membrane. These findings were considered typical of the late infantile variant of NCL. After delivery at term, a skin punch biopsy and a buffy coat preparation from the baby were examined and found to have similar characteristic inclusions, which confirmed our prenatal diagnosis.
X‐linked intellectual handicap and precocious puberty with obesity in carrier females
Authors: Hockey Athel , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractPrecocious puberty (PP) and intellectual handicap were present in 3 males in 2 generations of a Western Australian family. The 2 obligate carrier women were of normal intelligence but were grossly obese; one died of a cardio‐myopathy at 55 years.The youngest affected male was found to have PP at 3 years. His mother was then pregnant, and because of her family history, was aware of the risk to have an affected male. Her mother had given birth to 2 sons with PP. By school age both of these males were mildly intellectually handicapped and this later became moderate.Apart from these 3 affected males, the 2 carriers lost 6 of their other 8 offspring, leaving only one normal woman and her unaffected son.The Fragile X test was negative on all males. This appears to be a new X‐linked mental retardation syndrome, and a condition different from true idiopathic PP, or familial PP affecting both sexes, or PP with X‐linked dominant inheritance.
Cognitive profiles and the spectrum of clinical manifestations in heterozygous fra(X) females
Authors: Kemper Melinda B. , Hagerman Randi J. , Ahmad Razia S. , Mariner Robin , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe investigated the possibility that fra(X) heterozygotes had a distinct or specific set of mental deficits (“cognitive profile”) which would allow for accurate diagnosis. Wechsler Intelligence Scale for Children‐Revised (WISC‐R) subtest scores obtained on 8 fra(X) school age girls were compared with similar scores obtained on 8 “learning‐disabled” non fra(X) gils matched on the basis of Full Scale IQ (FSIQ). The Block Design subtest score was significantly lower in fra(X) girls. In a larger sample of 22 fra(X) females, a characteristic combination of low Arithmetic, Digit Span, and Block Design subtest scores was observed. The mean discrepancy between these 3 subtest scores from the total Verbal or Performance subtest means was significant for the fra(X) group but not for a comparison group of 20 learning‐disabled females. Verbal IQ (VIQ) and Performance IQ (PIQ) discrepancy was not significant in fra (X) females. Percent fra(X) positive cells was negatively correlated with VIQ and FSIQ but not with PIQ.
An analysis of autism in fifty males with the fragile X syndrome
Authors: Hagerman Randi J. , Jackson Alfred W. , Levitas Andrew , Rimland Bernard , Braden Marcia , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFifty males with the fragile X [fra(X)] syndrome, which we consider synonymous with the Martin‐Bell syndrome, were identified by a chromosome analysis of patients with developmental delays or mental retardation and family studies of known fra(X) pedigrees. These males were evaluated for autism using three criteria: (1) the DSM III diagnostic criteria for Infanti, Autism; 2) the Autism Behavior Checklist (ABC); and 3) the Diagnostic Checklist for Behavior Disturbed Children, Form E2. Sixteen percent of patients fulfilled all of the DSM III criteria for Infantile Autism and an additional 30% fulfilled criteria for Infantile Autism Residual State. Thirty‐one percent of patients had autism using the ABC checklist but none of the patients fit the classical Kanner syndrome as described by the E2 questionnaire. Some autistic traits were seen in almost all of the 50 fra(X) patients, including eye avoidance in 90%, handflapping, handbiting or handstereotypies in 88%, and language delays with language peculiarities, usually echolalic speech, in 96%. A pervasive lack of responsiveness was seen in 18% at their present age and in 44% in earlier childhood only.Autistic symptoms are common in the fra(X) syndrome. Therefore, any patient with developmental delays and autism or autistic manifestations should have a chromosomal analysis, including fra(X) examination.
Somatic cell hybrid studies of fragile (X) expression in a carrier female and transmitting male
Authors: Ledbetter David H. , Airhart Susan D. , Nussbaum Robert L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe have extended our previous studies of fra(X) expressionin somatic cell hydrids to the analysis of a carrier female with a low level of expression and to an unaffected, transmitting male who shows no expression in lymphocytes or lymphoblasts. Optimum conditions for fra(X) expression was treatment with 10−8 M FUdR for 16 hours. In recent experiments, addition of 2.2 mM caffeine 2 hours before harvest was found to increase expression consistently. Two clones from the carrier female containing the far(X) chromiosome but not the normal X showed expression of 2–4%, indicating that expression in heterozygous females is not influenced by the presence or absence of the normal X. Expression rate was increased to 20% by exposure to FUdR plus caffeine. Analysis of hybrids containing only the fra(X) in an inactive state, and after reactivation by 5‐azacytidine, showed no change in the frequency of expression. A hybrid clone from the nonexpressing, transmitting male containing only the X and chromosome 13, showed expression rangine from 2% without caffeine to 12% with caffeine in three different experiments. The ability to induce fra(X) expression n hybrid from this nonexpressing male may be explained in one of several ways: (1) a second mutation has occurred, (2) an autosomal suppressor locus was lost, or (3) the hamster genome or unusually short cell cycle lowers the threshold for expression, particularly in presence of caffeine.
Caffeine enhances fragile (X) expression in somatic cell hybrids
Authors: Ledbetter David H. , Airhart Susan D. , Nussbaum Robert L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractYunis and Soreng recently demonstrated enhanced expression of common fragile sites as and of fra(X) when 2.2 mM caffeine is added to FUdR treated lymphocyte cultures 6 hours before harvest. We failed to replicate this finding for fra(X) expression in we do find a consistent increase in expression levels in somatic cell hybrids between a Chinese hamster cell line and 3 unrelated individuals with the fra(X) mutation when caffeine is present for the last 2 hours before harvest. This was particularly true for “low‐expressing” cell lines, in which a 4‐6 fold increase was observed. Using a thymidylate synthase deficient hybrid which could be blocked in the S phase by thymidine deprivation, we found that caffeine significantly reduced the recovery time from thymidine release to mitosis. This produced the highest level of fra(X) expression (48%) only one hour after release from thymidine deprivation. These results show that caffeine does enhance fra(X) expression in at least some cell types. The effect is probably, inhibiting the mitotic delay usually associated with DNA damage.
A rodent‐human hybrid containing Xq24‐qter translocated to a hamster chromosome expresses the Xq27 folate‐sensitive fragile site
Authors: Nussbaum Robert L. , Airhart Susan D. , Ledbetter David H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA somatic cell hybrid containing a single human X chromosome hearing the Xq27 fragile site was lethally irradiated and re‐hybridized to its HPRT‐ Chinese hamster parent. One of 24 colonies surviving selection for HPRT was found to have retained human G6PD but not PGK. This line, X300‐11 which shows Xq24‐qter translocated to a hamster chromosome by trypsin G‐banding and a single human chromatin fragment corresponding to this segment of the X by G‐11 staining, expresse the fragile site on exposure to 5‐fluorodeoxyuridine. Dot blots using total human DNA suggest that X3000‐11 retains ∼0.2% of the human genome. By Southern blotting, X3000‐11 retains Factor IX, DXS11 and DXS42 but lacks DXYS1, DXS3 and DXS17. This hybrid is being used to construct a cosmid library in the vector pCOS2 from which a sub‐library of 500‐1000 clones of human origin will be isolated using in vivo recombination with cloned Alu and Kpn family repeats. Such a sub‐library will greatly facilitate chromosome walking to the fragile site as well as the testing fo individual clones for their ability ot create a folate‐sensitive fragile by DNA transfer into permissive Chinese hamster recipient cells.
Studies of the fragile (X) syndrome in populations of mentally retarded individuals in Hawaii
Authors: Jacobs Patricia A. , Mayer Martha , Abruzzo Michael A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThree populations of retarded individuals were surveyed and the frequency of the fra (X) was found to be 1.9% in males and 0.3% in females.
Population incidence and segregation ratios in the Martin‐Bell syndrome
Authors: Webb Tessa P. , Bundey Sarah E. , Thake Ann I. , Todd June , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA clinical and cytogenetic study of children attending schools for the educationally handicapped has been carried out in the City of Coventry. As a result of this an estimate of the population incidence of the Martin‐Bell syndrome among schoolchildren has been made. Among schoolboys the incidence of mental retardation dur to the fra(X) was found to be 0.73 per 1000 and among schoolgirls 0.48 per 1000. The overall prevalence is 0.61 per 1000. Genetic and cytogenetic analysis of 14 families ascertained in an unbiased manner showed that the expected 50% ratio of affected to unaffected relatives was disturbed, the possible result of a segregation distortion.
The Martin‐Bell syndrome in South Africa
Authors: Venter Philip A. , Hof Johann Op't , Coetzee Dennis J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA national screening programme was introduced in 1980 when the first cases with the Martin‐Bell syndrome were diagnosed in South Africa. This survey includes patients from all the major population groups in South Africa. One thousand patients, who include 354 relatives of 21 index cases, were investigated cytogenetically. About 75% of the 354 relatives were either affected males or obligate or possible carriers. The segregation pattern of the fragile site was investigated in 271 offspring of 58 carrier women. At least 30% of the carriers were mildly mentally retarded with most expressing the fragile site. Various other investigations, such as measurements of testes, speech, verbal and IQ evaluations and hormone studies were done on several affected males. No fragile site could be demonstrated in 57 unselected autistic children. The results of this programme show that this syndrome is a common cause of mental retardation and that prevention of mental retardation is possible if all the involved families could be identified.
Neonatal adrenoleukodystrophy: New cases, biochemical studies, and differentiation from Zellweger and related peroxisomal polydystrophy syndromes
Authors: Kelley Richard I. , Datta Nabanita S. , Dobyns William B. , Hajra Amiya K. , Moser Ann B. , Noetzel Michael J. , Zackai Elaine H. , Moser Hugo W. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractEight new cases of autopsy‐confirmed or suspected neonatal adrenoleukodystrophy (NALD) are presented together with new biochemical data on very‐longchain fatty acids (VLCFA) and plasmalogens and a review of all previously published cases. The clinica biochemical, and histopathologic abnormalities characteristic of this newly recognized form of adrenoleukodystrophy are analyzed in detail and compared to the principal characteristics of the similar disorder, the cerebrohepatorenal syndrome of Zellweger (ZS). Using strict pathologic criteria for the diagnosis of NALD, we find that, despite many clinical resemblances, NALD and the ZS are distinguishable on the basis of histology and peroxisomal biochemistry. Patients with NALD demonstrate adrenal atrophy, systemic infiltration by abnormal lipid‐laden macrophages, and elevations of saturated VLCFA. In contrast, patients with ZS have chondrodysplasia, glomerulocystic disease of the kidney, central nervous system dysmyelination, and elevations of unsaturated as well as saturated VLCFA, but they lack adrenal atrophy. We conclude that NALD and the ZS probably represent at least two different genetic defects.
An association of prune belly anomaly with trisomy 21
Authors: Amacker Elizabeth A. , Grass Frank S. , Hickey Docia E. , Hisley John C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on two patients wth prune belly anomaly (PBA) and trisomy 21 documented by clinical examination and cytogenetic investigation. The first infant was diagnosed at birth. A distended bladder was detected prenatally by ultrasound in the second, and chromosome studies were performed on cells obtained from fetal “bladdercentesis.” We discuss the importance of cytogenetic studies in cases where fetal surgery is a consideration.
A re‐examination of major locus hypotheses for high density lipoprotein cholesterol level using 2,170 persons screened in 55 Utah pedigrees
Authors: Hasstedt Sandra J. , Ash K. Owen , Williams Roger R. , Reynolds James F. 
Published: June 2005

AbstractA dominant major locus (allele frequency of .0025 ± .0014), resulting in low levels of high density lipoprotein cholesterol (HDL‐C), was revealed by likelihood analysis on 2,170 persons in 55 Utah pedigrees. This allele was expressed through HDL‐C levels ranging from 20 to 30 mg/dl in seven persons in two pedigrees. Early coronary heart disease was associated with the allele in one pedigree, but not in the other. In the pedigree without associated heart disease, HDL subfractions HDL2 and HDL3 were both low in individuals with the low HDL‐C allele. No other major locus determining either high or low levels of HDL‐C was identified in our sample. Polygenic heritability as part of the mixed model was estimated as .561 ± .035.
Zellweger syndrome: Diagnostic assays, syndrome delineation, and potential therapy
Authors: Wilson Golder N. , Holmes Ronald G. , Custer Joseph , Lipkowitz Jeffrey L. , Stover Joan , Datta Nabanita , Hajra Amiya , Reynolds James F. 
Published: June 2005

AbstractPatients with the cerebrohepatorenal syndrome of Zellweger lack peroxisomes and certain peroxisomal enzymes such as dihydroxyacetone phosphate acyltransferase in their tissues. Deficiency of this enzyme, which is necessary for glycerol ether lipid synthesis, provides a biochemical method for recognizing patients with subtle manifestations of Zellweger syndrome and suggests the utility of exogenous ether lipid precursors as a therapeutic strategy for these children. We describe the results of glycerol ether lipid supplementation to two children, one with classic Zellweger syndrome and 9% of control fibroblast dihydroxyacetone phosphate acyltransferase activity, and one with mild facial manifestations, wide sutures, hypotonia, developmental delay, hepatomegaly, peripheral retinal pigmentation, and 50% of control fibroblast dihydroxyacetone phosphate acyltransferase activity. An increase in erythrocyte plasmalogen levels following therapy was clearly demonstrated in the milder patient, and neither patient showed evidence of toxicity. Evaluation of therapy by comparison to the usual clinical course of Zellweger syndrome was not helpful because of the variability and incomplete documentation of 90 previously reported cases. The literature survey did provide criteria for classic Zellweger syndrome, which include hypotonia with or without deformation of limbs, large fontanels and split sutures, prominent forehead, flattened facial profile with hypoplastic supraorbital ridges, anteverted nares, highly arched palate, cryptorchidism or labial hypoplasia, hepatomegaly or elevated liver enzymes, peripheral pigmentation of the retina, renal cortical cysts, and characteristic neuropathology involving decreased myelinization, abnormal neuronal migration, and sudanophilic macrophages. Less severe patients, as exemplified by our case 2 and others from the literature, will not have all the classic features and can be recognized only by a growing panel of biochemical indicators. Our patient studies illustrate the complexity of designing comprehensive therapy for Zellweger‐like conditions, suggest other diseases that may involve peroxisomal alterations, and emphasize the need for multicenter, collaborative studies to evaluate biochemical heterogeneity and therapy of peroxisomal disorders.