bluuebunny/crossref_metadata_2025_split huggingface dataset:
In vivo alteration of a mutant human protein using the free thiol cysteamine
Authors: Gahl William A. , Gregg Richard E. , Hoeg Jeffrey M. , Fisher Edward 
Published: June 2005

AbstractInborn errors of metabolism in which there is a mutant protein due to a cysteine for arginine substitution may be evidence for this derives from patients with type III hyperlipoproteinemia, who are homozygous for apolipoprotein E2, which differs in charge and in vitro function basedon a single such amino acid substitution. The plasma of a type III hyperlipoproteinemic patient, when made at least 50m with respect to cysteamine in vitro, demonstrated a charge shift of the apolipoprotein E isoelectric focusing pattern from the E2 to the normal E3 and E4 positions. Two Children treated for cystinosis with cysteamine each exhibted some charge alteration of their apoE3 to a form migrating in the apoE4 position. The use of thiol reagents such as cysteamine to specifically alter selected mutant human proteins, such as antithrombin III Toyama, may be added to our therapeutic armamentarium in the treatment of life‐threatening metabolic disorders.
An unusual distal arthrogryposis
Authors: Kawira Esther Lehman , Bender Harvey A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe report on a mother and her dizygotic twin fetuses who were affected with distal arthrogryposis. In addition the mother has cervical vertebral anomalies, scoliosis, short stature, nuchal and axillary pterygia, and unusual facial appearance. The fetuses had a short neck, pterygium colli, retrognathia, and mild apparent scoliosis. We think that these three individuals have a previously undescribed type of distal arthrogryposis.
Hypergonadotropic hypogonadism with congestive cardiomyopathy: An autosomal‐recessive disorder?
Authors: Malouf Joe , Alam Samir , Kanj Hassan , Mufarrij Amjad , Der Kaloustian Vazken M. 
Published: June 2005

AbstractWe report on two sisters with ovarian dysgenesis and secondary hypergonadotropic hypogonadism and congestive cardiomyopathy. Their parents are first cousins. It is suggested that these are the main manifestations of a previously unreported autosomal‐recessive syndrome.
A thermolabile variant of α‐L‐fucosidase—clinical and laboratory findings
Authors: Blitzer Miriam G. , Sutton Millicent , Miller James B. , Shapira Emmanuel , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA family with two sibs affected clinically with the severe infantile form of fucosidosis is described. Biochemical studies revealed a relatively high residual activity (34–60% of normal) with markedly decreased thermostability. The importance of including thin layer chromatography for urinary oligosaccharides in the diagnostic workup for such patients is emphasized.
Vesicoureteric reflux: Segregation analysis
Authors: Chapman C. J. , Bailey R. R. , Janus E. D. , Abbott G. D. , Lynn K. L. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractComplex segregation analysis was applied to data from 88 families containing at least one person with vesicoureteric reflux. Analysis showed that a single major locus was the most important causal factor in this condition, with the mutant allele being dominant to the normal allele and having a gene frequency of about 0.16% Forty‐five percent of gene carriers will have vesicoureteric reflux and/or reflux nephropathy as adults and 15% will develop renal failure, compared to 0.05% and 0.001%, respectively, for those not carrying the gene. This analysis confirms the importance of screening close relatives of persons with proven vesicoureteric reflux or reflux nephropathy.
Anomalies associated with cleft lip, cleft palate, or both
Authors: Shprintzen Robert J. , Siegel‐Sadewitz Vicki L. , Amato John , Goldberg Rosalie B. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractNumerous investigators have reported on a low frequency of other anomalies in patients with cleft lip, cleft palate, or both. The data have been somewhat inconsistent, ranging from a 3% to over 30% frequency of associated malformations. However, a recent study concluded that over half of the children with clefts at a large metropolitan center have associated anomalies. In an effort to elucidate further the genetic and morphologic characteristics of patients with clefts, 1,000 patients with clefts of the lip, palate, or both were examined and reviewed. The results indicate that associated anomalies occur in 63.4% of the sample. Approximately half of the patients with multiple anomalies have recognized syndromes, sequences, or associations, while the other half have physical examination (apparently one‐of‐a‐kind) syndromes. The high frequency of associated anomalies has obvious implications for the genetic counseling offered to all patients at cleft palate and craniofacial centers. The frequency of associated anomalies also raises questions regarding the validity of past genetic research involving populations of subjects with clefts.
Familial microcephaly with normal intelligence, immunodeficiency, and risk for lymphoreticular malignancies: A new autosomal recessive disorder
Authors: Seemanová Eva , Passarge E. , Beneškova Dagmar , Houštěk J. , Kasal P. , Ševčìková Melanie , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe nine patients with an apparently new genetic disorder characterized by: 1 (microcephaly with normal intelligence; 2) “bird”‐like facial appearance; 3( cellular and humoral immune defects; and 4) increased risk for lymphoreticular malignancies. The postmortem findings of five patients are described. Chromosome instability appears not to be a component of the disorder. The occurrence in three pairs of sibs and isonomy in another family suggests autosomal recessive inheritance.
The effect of Mendelian disease on human health: A measurement
Authors: Costa Teresa , Scriver Charles R. , Childs Barton , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe an attempt to measure effects of Mendelian phenotypes on human health (homeostasis) in man. We used the McKusick Catalogs as the source for descriptions of autosomal dominant, recessive, and X‐linked phenotypes. Three hundred and fifty one entries (76% of the initial sample) were disadaptive causing an impairment, disability, or handicap. (Terms used are in accordance with World Health Organization (WHO) definitions.) Phenotypic effects were scored to measure impact on life‐span, reproductive capability, and psychosocial characteristics. We found 1) 25% of the disadaptive Mendelian phenotypes were apparent at birth and over 90% by the end of puberty; age at onset is unimodal in distribution for autosomal recessive and X‐linked diseases, and trimodal for autosomal dominant (with modes during morphogenesis, infancy, and early adult life); 2) 58% of phenotypes involved more than one anatomical or functional system; autosomal dominants were more likely to involve only a single system; 3) life‐span was reduced in 57%, particularly in those with onset in pre‐ or intra‐reproductive life, and more often in recessive and X‐linked diseases (data corrected for genetic lethals); prognosis varied with system involvement; 4) reproductive capability was impaired in 69% of phenotypes; and 5) most phenotypes compatible with life beyond infancy caused psychosocial handicap and limited the access to schooling and work. These findings have implications for medical care.
The effect of Mendelian disease on human health. II: Response to treatment
Authors: Hayes Ailish , Costa Teresa , Scriver Charles R. , Childs Barton , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe describe an attempt to measure efficacy of treatment in the Mendelian diseases of man. We used the McKusick Catalogs to identify 351 single gene diseases. We scored the impact of each disease in seven phenotypic categories: lifespan, reproductive capability, somatic growth, intellectual development, learning ability, capacity to work, and cosmetic effect. We then scored the success of treatment in ameliorating each of these component manifestations separately and together. The response to treatment was slight in the whole sample (n = 351): lifespan was increased in 15%, reproductive capability in 11%, and social adaptation in 6%. We observed that the mutant gene product was known in only 15% of the conditions comprising our sample. Since the mutant polypeptide is known in most inborn errors of metabolism, the diseases of this type (n = 65) in our sample of Mendelian traits were studied separately. In each of the seven categories of phenotypic impact, only a few of the hereditary metabolic diseases responded in any degreee to specific treatment: the treatment gave complete relief in 12%, there was a partial response in 40%, and none in the remaining 48%. These findings have implications for prognosis, genetic counseling, and medical care of patients with Mendelian disease.
Paternity testing with genetic markers: Are Y‐linked genes more efficient than autosomal ones?
Authors: Chakraborty Ranajit , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe average probability of exclusion for a Y‐linked locus is computed and compared with that for an autosomal locus. It is shown that even if a Y‐linked locus is only marginally polymorphic, it considerably enhances the chance of paternity exclusion in paternity dispute cases involving sons. For the positive identification of paternity, a Y‐linked marker is not necessarily more ideal than an analogous autosomal marker since the discrimination of true fathers from random men not excluded from paternity (RMNEP) is still difficult on the basis of a paternity index. It is concluded that Y‐linked markers are more efficient for paternity exclusions of male children, while for the positive identification of paternity their advantages over the autosomal markers are questionable.
Anthropometric discrimination among affected, at‐risk, and not‐at‐risk individuals in families with Huntington disease
Authors: Farrer Lindsay A. , Yu Pao‐Io , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractAn earlier report showed significant differences among Huntington disease (HD) patients, controls, and particular age cohorts of at‐risk persons for several dimensions of body mass and for several linear and craniofacial components of the body. In this investigation a function was derived from a stepwise discriminant analysis of the affected and unaffected groups, and used to classify the at‐risk individuals according to HD gene carrier status. The function, comprised of body mass index, subscapular skinfold, head length, and sitting height, classified 95% of the controls and 87% of the affected individuals correctly. Approximately 80% of the individuals at‐risk were classified with 80% or greater certainty.We propose that anthropometric variables may prove to be a powerful tool for basic research in HD and the derived discriminant function has potential clinical value as a diagnostic and preclinical diagnostic aid. We emphasize that corroborative testing on other sample populations of HD families is required before these techniques are utilized. Also, it is imperative that the anthropometric protocol include appropriate standardization of the raw measurement data.
A method to assess the environment for genetic studies: The common environment index and the household relationships interview
Authors: Hunter Saundra MacD , Rosenbaum Peter A. , Borecki Ingrid B. , Elston Robert C. , Berenson Gerald S. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractGenetic and environmental influences in causing a disease are difficult to measure because of lack of precision in identification of relevant nongenetic variables.The Household Relationships Interview and Schedule was developed to measure shared common environment in families (Common Environment Index) and to take into account developmental stages throughout the life cycle and separation/ disruption. Seven trained persons interviewed three individuals who reported fictitious interrelated life histories varying in length and complexity. Discrepancies between the recorded data and the true data were analyzed. Overall 96.1% of the items were recorded correctly. Thus, the method has shown good face and construct validity and reliability for measuring quantity of time shared by relatives in a common household. Common environment as measured by this instrument should be a particularly useful tool in behavior–genetic studies.
Enhanced expression of chromosome fragile site 10q25 in chronic myelogenous leukemia
Authors: Morgan Rodman , Morgan Stephanie S. , Hecht Frederick , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSpontaneous expression of a BrdU‐sensitive fragile site at 10q25 was observed in normal lymphocytes and malignant blood and bone marrow cells in chronic myelogenous leukemia (CML). The cells were marked by a Philadelphia chromosome rearrangement due to insertion of 22q11 → q13 at 11q13. The fragile site at 10q25 was expressed in larger proportions of malignant than normal cells. Although this fragile site is not at a cancer chromosome breakpoint, malignancy enhanced its expression, consistent with a cascade effect.
The heterogeneity problem. I: Separating genetic from environmental forms of the same disease
Authors: Greenberg David A. , Hodge Susan E. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThe purposes of this work were 1) to reparameterize the likelihood used in segregation analysis in a way particularly suited to detecting heterogeneity (the result of the analysis is a parameter giving the proportion of families with the genetic form of the disease in the dataset) and 2) to test how well this reparameterization works using simulation.We assume that a dataset contains nuclear family data, with some of the families having a form of the disease that is environmentally caused and the others with a genetic form of the disease. In this study, we considered the case where the genetic form is a simple recessive and the environmental form a random model. The underlying parameters were the gene frequency, q, and the frequency of sporadics, R. We reparameterized the likelihood in terms of α, the percentage of genetic families in the dataset, which we attempt to estimate. We contrast the estimates of α with the population heterogeneity as reflected in the estimates of q and R.For the simulation, nuclear families are generated. Genetic families were simulated with a mendelian recessive pattern and environmental families according to a simple random model.Over a wide range of generating parameters, estimates of α were good, differing from the “true” values by only a few percent. Estimates of q and R, on the other hand, ranged from fair to poor. Our results indicate that the amount of heterogeneity in a dataset can be accurately estimated using segregation analysis, even when estimates of the gene frequency and penetrance among sporadics are unreliable.
Genetic heterogeneity in Gaucher disease: Physicokinetic and immunologic studies of the residual enzyme in cultured fibroblasts from non‐neuronopathic and neuronopathic patients
Authors: Grabowski Gregory A. , Goldblatt Jack , Dinur Tama , Kruse Joanne , Svennerholm Lars , Gatt Shimon , Desnick Robert J. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractTo elucidate the genetic heterogeneity in the three major phenotypic subtypes of Gaucher disease, the residual acid β‐glucosidase in fibroblasts from patients with all three subtypes from different ethnic and demographic groups was investigated by comparative kinetic, thermostability, and immunotitration studies. The kinetic studies delineated three distinct groups (designated A, B, and C) of residual activities with characteristic responses to the enzyme modifiers, taurocholate (or phosphatidylserine), and glucosyl sphingosine (or N‐hexyl glucosyl sphingosine); Group A residual enzymes responded normally to these modifiers. All neuronopathic patients (types 2 and 3) and most non‐Jewish, non‐neuronopathic patients (type 1) had group A residual activities and thus could not be distinguished by their kinetic properties. Group B residual enzymes had markedly abnormal responses to these modifiers. All Ashkenazi and only two non‐Jewish type 1 patients had group B residual activities. Group C residual activity had an intermediate response to all modifiers and represented a single Afrikaner type 1 patient. Pedigree studies indicated that this patient was a genetic compound for the group A (type 2) and group B (type 1) mutations. Thermostability studies showed additional heterogeneity of the residual activities within the three kinetic groups. Group A (type 2) and group B (type 1) enzymes had similarily decreased thermostabilities. In contrast, group A (type 1) residual activities were heterogeneous; three classes of thermostabilities were found among these enzymes: normal, decreased, and increased Immunotitration of equal amonuts of the normal or Gaucher dieseas β‐glucosidase activities with monospecific IgG indicated that the enzyme proteins from most Gaucher disease patients were antigenically altered and/or that large amounts of catalytically abnormal or inactive antigen were present. A decreased amount of antigenically and catalytically normal enzyme was present in a group A, type 1 African black patient, suggesting decreased stability or synthesis of his mutant acid β‐glucosidase. These kinetic, immunologic, and thermostability studies indicated that 1 type (1) Gaucher disease is biochemically heterogeneous and results from at least from distinct allelic acid β‐glucosidase mutations that alter enzyme structuer and/or function, 2 neuronopathic and non‐Jewish non‐neuronopathic phenotypes cannot be distinguished reliably by kinetic analyses alone, and 3) the Ashkenzi type 1 Gaucher disease results from a unique mutation that alters a specific active site domain of acid β‐glucosidase.
Similarity of effects—experimental hyperthermia as a teratogen and maternal febrile illness associated with oromandibular and limb defects
Authors: Superneau Duane W. , Wertelecki Wladimir , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractExperimental hyperthermia in pregnancy causes oromandibular and limb anomalies. In humans, hyperthermia has been suspected of being teratogenic. Two patients were investigated; both had limb defects and one had oromandibular anomalies. Their mothers had a febrile illness at about the 10th wk of gestation. The similarity of defects produced by experimental hyperthermia and those reported here is striking.
Chondrodysplasia punctata in an infant with duplication 16p due to a 7;16 translocation
Authors: Hunter Alasdair G. W. , Rimoin David L. , Koch Ulrike M. , MacDonald G. June , Cox David M. , Lachman Ralph S. , Adomian Gerald , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThis paper describes a newborn with a number of clinical manifestations compatible with duplication 16p due to a 46, XY, −7, +der (7), t(7;16) (p22;p13) pat karyotype. In addition, the baby had chondrodysplasia punctata, whose distribution of lesions did not match any of the well‐documented forms of these disorders. The baby also had microcornea and lacked a gallbladder, two features, in addition to chondrodysplasia punctata, that have not previously been noted in cases of duplication 16p.
Variance components analysis of forced expiration in families
Authors: Astemborski J. A. , Beaty T. H. , Cohen B. H. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractFamilial aggregation of forced expiration (as measured by forced expiratory volume in 1 sec (FEV1) and the ratio of this to total forced vital capacity (FEV1/FVC) was analyzed in 439 adult members of 108 families ascertained through control patients who had participated in a genetic and epidemiologic study of chronic obstructive pulmonary disease. Residual values for both FEV1 and FEV1/FVC obtained from regression on age, sex, race, and cigarette smoking (and height for FEV1) were used in a variance components analysis to assess the relative importance of genetic and nongenetic factors influencing familial aggregation of pulmonary function among adults.For both residual FEV1 and residual FEV1/FVC, the “best” model among a series of genetic and nongenetic models was a simple additive genetic model. A modified score test, which is robust to the assumption of multivariate normality, was used to test the significance of these estimated components. Under the most parsimonious model, additive genetic variation accounted for 28% of the variation in residual FEV1 in 108 families and 24% of the variation in residual FEV1/FVC. After outlying individuals were identified by examining goodness‐of‐fit statistics, the simple genetic model still gave the best fit to these data. There was little indication of non‐normality in FEV1 in these families; however, FEV1/FVC did show evidence of non‐normality when examining goodness‐of‐fit statistics. This genetic component contributing to the distribution of forced expiration may be a factor in the familial aggregation of certain respiratory diseases.
Apical hypertrophic cardiomyopathy in a father and daughter
Authors: Malouf Joe , Ratl Habib , Der Kaloustian Vazken M. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractApical hypertrophic cardiomyopathy is described in a father and his daughter. In both, identical segments of the left ventricle were involved by the hypertrophic process with differing degrees of severity. We suggest that the morphologic findings described are due to a single gene with an autosomal dominant mode of inheritance.
Serum CK‐MB activity in progressive muscular dystrophy: Is it of nosologic value?
Authors: Vainzof Mariz , Zatz Mayana , Otto Paulo A. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractSerum creatine‐kinase (CK) isoenzyme MB was measured in 53 patients affected by different types of myopathies (20 with Duchenne muscular dystrophy (DMD), eight with the Becker form (BMD), ten with the limb‐girdle form (LGMD), six with the facioscapulohumeral form (FSH), and nine affected by polymyositis and in 21 normal control subjects).The aim of this study was to compare each group with the control individuals and to assess the nosologic value of CK‐MB activity among some clinically similar dystrophies, which may have an important application for genetic counseling.A statistically significant increased CK‐MB activity was found only in the Duchenne and Becker patients when compared with control persons (p < 0.05).When the different groups of patients were compared among themselves, no significant difference was found between DMD and BMD or LGMD and polymyositis. However, a significant difference was found between BMD and LGMD.Based on these data, it is possible, through discriminant analysis, to estimate the relative biochemical probability of an isolated male patient belonging to either group.
Further delineation of the dup(3q) syndrome
Authors: Wilson Golder N. , Dasouki Majed , Barr Mason , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractThree patients with duplication of 3q regions ranging from 3q25→qter to the entire long arm provide additional documentation of the dup(3q) malformation syndrome. Data on 40 cases now reported define a characteristic face with hirsutism, synophrys, broad nasal root, anteverted nares, downturned corners of the mouth, micrognathia, and malformed ears recognizable even in the 30‐week fetus and distinct from that of the Brachmann‐de Lange syndrome. Other characteristic anomalies include congenital heart anomalies involving primarily septal defects, hand malformations including simian creases, abnormal dermatoglyphics, clinodactyly or camptodactyly, omphalocele, skeletal anomalies, and genitourinary malformations. Severe mental and growth retardation are common in those patients (64%) who survive the first year. Chromosome study of relatives is extremely important for counseling because only 10 of 40 cases represented de novo duplications.