bluuebunny/crossref_metadata_2025_split huggingface dataset:
The effects of reduced fertility, method of ascertainment, and a second unlinked locus on affected sib‐pair marker allele sharing
Authors: Risch N. , Opitz John M. 
Published: June 2005

AbstractThe method of affected sib‐pair marker allele sharing has been used not only for the detection of linkage, but also for discerning inheritance. The application of this method has included the tacit assumption of no selective disadvantage for affected individuals. For some of the disorders analyzed by this method, this assumption is not tenable. Also, the method of ascertainment of affected sib pairs is not taken into account. It is shown here that the ascertainement procedure and reduced reproductivity of affected individuals can alter the expected distribution of affected sib‐pair marker allele sharing. The effect is greatest for a recessive disease susceptibility locus. While the effect of reduced reproductivity is to inflate the gene frequency necessary to account for the observed distribution, a second unlinked disease susceptibility locus can diminish this effect. Application to type 1 diabetes shows that according to a simple recessive model with 50% penetrance, to observed distribution of affected sib‐pair HLA haplotype sharing requires a gene frequency in the range of 0.55–0.60, much greater than estimates previously proposed. According to such a model, the frequency of disease would be around 15%, clearly out to range of the observed frequency of 0.4%.
A familial reciprocal translocation t(3;7) (p21.1;p13) associated with the Greig polysyndactyly‐craniofacial anomalies syndrome
Authors: Tommerup Niels , Nielsen Frank , Opitz John M. 
Published: June 2005

AbstractA translocation t(3;7) (p21.1;p13) segregating through four generations was found to be invariably associated with the Greig cephalopolysyndactyly syndrome (GS). High resolution chromosome analyses using G and R banding did not uncover any imbalance of the affected chromosomes, nor were the late replicating patterns changed. One girl with the GS died of a medulloblastoma.
Ring chromosome 21 in phenotypically apparently normal persons: Report of two families from Switzerland and Italy
Authors: Schmid Werner , Tenconi Romano , Baccichetti Carlo , Caufin Daniele , Schinzel Albert 
Published: June 2005

AbstractIf a ring 21, originating from breaks close to the telomere of 21q and anywhere in 21p, replaces a normal 21, it may be associated with an apparently normal phenotype. An apparently normal mother and son were ascertained by a prenatal chromosome study. A second mother, with a ring 21 but without gross anomalies, is short of stature, has epilepsy, and has a low normal intelligence. Her daughter is a mosaic: 46, XX/47, XX, + r(21) and has the Down's syndrome. None of these four persons was found to have mitoses with more than one ring 21 or with rings of double size.
Inbreeding studies in Brasilian schoolchildren
Authors: Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , de Aguiar‐Wolter Iêda P. , Azevedo‐Fialho Maria da Graça , de Azevedo M. Barros , Krieger H. , Barbosa C. A. A. , Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , Barbosa C. A. A. , Krieger H. , Cat I. , Marinoni Leide P. , Giraldi D. J. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Cat I. , Giraldi D. J. , Marinoni Leide P. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Müller Valderez S. , Chautard‐Freire‐Maia E. A. , Freire‐Maia N. , Krieger H. , Barbosa C. A. A. , Monte‐Serrat Ísis S. , Freire‐Maia N. , Chautard‐Freire‐Maia E. A. , Kreiger H. , Barbosa C. A. A. 
Published: June 2005

AbstractWe present results of comparisons between consanguineous and control couples and their children in Southern Brasil. Multiple regression, t‐test and χ2 analyses were applied to the data. The following variables were investigated; Parents: structure of first cousin marriages, latitude and longitude of birthplaces, cohabitation time, rurality, marriage age, occupation, number of liveborn children, and frequency of twinning. Schoolchildren: clinical data as classified into 24 discontinuous traits, each one subdivided into two categories (number and severity), and seven continuous traits (weight, height, pulse rate, respiratory rate, systolic pressure, diastolic pressure, and temperature); nutrition indices and biotype; family names; intelligence tests and school performances; birth order, age, hair color, hair type, eye color, and skin color; twinning in the sibship, and infant mortality among sibs of the propositi.Our study showed a) nonrandomness of consanguineous marriages as detected on structural, racial, geographical, and temporal levels; b) a heavy mutational load of about 1.5 lethons acting on infant mortality; c) no inbreeding effect on morbidity in general (with a possible exception of “ear morbidity”, including hearing deficit); d) a modest inbreeding depression on height (a decrease of 2 cm with an increase of 10% of inbreeding); e) a suggestion of inbreeding depression on “intelligence”.
Creatine‐kinase (CK) and pyruvate‐kinase (PK) activities in cord blood of normal newborn infants: Application to duchenne muscular dystrophy screening programs
Authors: Passos Maria Rita , Zatz Mayana 
Published: June 2005

AbstractCreatine‐kinase (CK) and pyruvate‐kinase (PK) were determined in cord blood samples from 125 normal newborn infants in order 1) to investigate the correlation between CK and PK, 2) to evaluate a possible influence of the mode of delivery (cesarean section versus vaginal delivery) and birth weight on enzyme activity, 3) to establish normal values for both sexes. In the present investigation, the enzyme activities of cord blood were significantly higher than in the normal adult, and no correlation was observed between enzyme activity and mode of delivery or birthweight.Although there was an apparent and significant correlation (r = 0.5) between CK and PK levels in cord blood samples, in no case did we find both high CK and PK values, something that would suggest preclinical DMD or a false‐positive result.These results have led us to suggest determination of serum PK activity in male newborn screening programs. This would allow an early discrimination between false‐positives and preclinical cases already in the neonatal period. Furthermore, the concomitant use of PK and CK in boys not walking by 18 months could be a useful test for diagnosing preclinical DMD boys.
A new X‐linked mental retardation‐overgrowth syndrome
Authors: Golabi Mahin , Rosen Linda , Opitz John M. 
Published: June 2005

AbstractWe report on a family with 4 affected males in 3 generations with a previously unreported X‐linked mental retardation/multiple congenital anomaly (XLMR/MCA) syndrome. The propositus was a 7‐year‐old Latin American moderately retarded male with; prenatal and postnatal overgrowth; short, broad upturned nose; large mouth; midline groove of tongue, lower alveolar ridge and lower lip; submucous cleft palate; supernumerary nipples; 13 ribs; Meckel's diverticulum; intestinal malrotation; coccygeal skin tag and bony appendage; hypoplastic index fingernails; postaxial polydactyly of the right hand, bilateral syndactyly of 2nd and 3rd fingers; and tibial clinodactyly of 2nd toes. His sister's son, a premature infant who died at 4 months, had nearly identical manifestations. The propositus and his nephew had normal chromosomes. A brother and son of the sister of the mother of the propositus were similarly affected and both died in the newborn period. The mother of the propositus had a large mouth, coccygeal skin tag and bony appendage, and hypoplastic index fingernails.This distinct mental retardation/multiple congenital anomaly syndrome is added to the growing list of presently known X‐linked MCA/MR syndromes.
A new X‐linked multiple congenital anomalies/ mental retardation syndrome
Authors: Golabi Mahin , Ito Melani , Hall Bryan D. , Opitz John M. 
Published: June 2005

AbstractWe report on 2 boys, the sons of sisters, and their mother's brother who have a new, X‐linked multiple congenital anomalies/mental retardation (MCA/MR) syndrome. The propositus was a 16‐month‐old caucasian male with 1)mental retardation, 2) congenital microcephaly, 3)postnatal growth deficiency, 4)ridged metopic suture with narrow bifrontal diameter, 5)upslanted palpebral fissures with persistent epicanthal folds, strabismus, and lacrimal duct obstruction, 6)narrow palate, 7)macrodontia, 8)anteverted ears, 9)atrial septal defect, 10)dry brittle scalp hair and 11)cutis marmorata. His chromosomes were normal. His cousin and uncle were similarly affected. This distinctive MCA/MR syndrome is added to the list of X‐linked malformation syndromes known at the present time.
Osteogenesis imperfecta type II delineation of the phenotype with reference to genetic heterogeneity
Authors: Sillence D. O. , Barlow K. K. , Garber A. P. , Hall J. G. , Rimoin D. L. 
Published: June 2005

AbstractA group of fetuses with a perinatally lethal variety of osteogenesis imperfecta (O.I. type II) is charaterized by short limbs, and clinical and roentgenological evidence of severe osseous fragility and defective ossification. Forty‐eight cases were reviewed and can be subdivided into 3 groups on the basis of small but probably significant differences in clinical and radiographic findings. Group A (38 cases): short, broad, “crumpled” long bones, angulation of tibiae and continuously beaded ribs. Group B (6 cases): short, broad, crumpled femora, angulation of tibiae but normal ribs or ribs with incomplete beading. Group C (4 cases): long, thin, inadequately modelled, rectangular long bones with multiple fractures and thin beaded ribs. Consistency of findings within sibships suggests the groups reflect genetic heterogeneity.An increased frequency of parental consanguinity, sib occurrence with normal parents, and normal mean paternal age at birth, suggest that most cases of O.I. type II represent autosomal recessive traits.Some previously reported cases and the biochemical findings in one case suggest still further genetic heterogeneity.
Familial congenital diaphragmatic defects: Aspects of etiology, prenatal diagnosis, and treatment
Authors: Norio Reijo , Kääriäinen Helena , Rapola Juhani , Herva Ritta , Kekomäki Martti 
Published: June 2005

AbstractWe present 14 familial cases from five Finnish families affected with a life‐threatening congenital diaphragmatic defect (CDD) and review data on 53 previously published familial cases. CDD occurred in three sibs and their half brother's son, and probably in all four offspring of parents consanguineous as both first and second cousins. In the remaining three Finnish families and in the vast majority of the previously reported familial cases, only two sibs were affected. Two thirds of those affected were males both in the Finnish and the overall series.Pedigree data, delayed fusion of the diaphragm as the primary pathogenetic mechanism, varying anatomical structure of the defective hemidiaphragm, association with other congenital anomalies, and data on animal experiments are more in accordance with multifactorial determination than with recessive inheritance. This does not exclude other genetic causes in some familial cases.The recurrence risk for sibs after one affected sib is about 2%. As the prognosis, especially in familial cases of CDD has remained grave, the development of fetal surgical treatment is desirable. This emphasizes the future role of prenatal diagnosis by ultrasound.
Duplication of distal 17q: Report of an observation
Authors: Naccache Nadyr F. , Vianna‐Morgante Angela M. , Richieri‐Costa A. , Opitz John M. 
Published: June 2005

AbstractWe describe a boy with the syndrome due to dup(17q) resulting from a paternal balanced t(12;17) (q24;q23). The comparison of the clinical findings in our patient with those previously reported shows that the dup(17q23 → qter) is associated with a clinically recognizable syndrome. Anomalies present in ≥ 75% of the patients were severe psychomotor retardation; short stature; microcephaly; frontal bossing and temporal retraction; widow's peak; narrow palpebral fissures; flat nasal bridge; thin upper lip overlapping thin lower lip; downturned corners of the mouth; apparently low‐set, posteriorly angulated and malformed ears; low posterior hairline; widely spaced nipples; cryptorchidism; proximal limb shortness; and hyperlaxity of limb joints.The translocation carrier father of our patient had a Poland anomaly.
Heterozygote detection in hunter syndrome
Authors: Zlotogora Joël , Bach Gideon 
Published: June 2005

AbstractIduronate sulfate sulfatase activity was determined in 36 women, relatives of Hunter syndrome patients. The use of serum and lymphocyte extracts for the determination of enzyme levels enabled the detection of 13 out of 15 (86%) obligate heterozygotes and identification of 10 of 21 other relatives as carriers. These methods are relatively simple and can easily be applied for routine examinations of all women at risk of being a Hunter heterozygote. These results permit for the first time meaningful genetic counseling for the families of Hunter patients.
Prune belly syndrome: Observations supporting the hypothesis of abdominal overdistention
Authors: Burton Barbara K. , Dillard Robert G. , Opitz John M. 
Published: June 2005

AbstractWe report on an infant with the prune belly syndrome who was unusual in that the typical manifestations of the disorder were accompanied by an anterior abdominal wall defect. We speculate that this defect may have occurred as a result of splitting of the abdominal wall secondary to massive bladder dilatation and stretching of the abdominal muscles. An alternative explanation is that the defect may have been the result of secondary pressure necrosis from stretching forces or from contact with another structure, such as the cervix. This case lends further support to the hypothesis that bladder distention with overdistention of the abdomen may be the primary event leading to the findings observed in the prune belly syndrome.
Linkage analysis in a large kindred with autosomal dominant transmission of polyglandular autoimmune disease type II (Schmidt syndrome)
Authors: Butler Merlin G. , Hodes M. E. , Conneally P. M. , Biegel Angenieta A. , Wright James C. , Opitz John M. 
Published: June 2005

AbstractSchmidt syndrome (PGA syndrome type II) is a rare condition characterized by polyglandular failure. It is an autosomal dominant trait with variable expressivity that was inherited over four generations in an Indiana kindred. Association of HLA‐B8 has been reported with Schmidt syndrome. Our proband is a 12‐year‐old boy with Addison disease, insulin dependent diabetes mellitus (IDDM), and vitiligo. Two of his eight sibs had either IDDM (sister) or vitiligo and hyperthyroidism (brother). His mother had hypothyroidism. Seven members of earlier generations apparently were also affected. We obtained peripheral blood for HLA and genetic analysis from 21 relatives in a family with 8 Schmidt syndrome individuals in three generations. HLA studies on 15 affected and unaffected relatives showed only 2 of 7 persons with B8‐containing haplotypes. Therefore, no association exists between the B8‐containing haplotype and the syndrome.We identified informative marker loci. No evidence for linkage of the Schmidt locus to any of the 14 markers was found and close linkage to esterase D and adenylate kinase and possibly properdin factor B was excluded.
Genetic counseling and reproductive uncertainty
Authors: Wertz Dorothy C. , Sorenson James R. , Heeren Timothy C. , Opitz John M. 
Published: June 2005

AbstractOf 836 fertile women seeking genetic counseling, 544 (65%) reported that their major reason for doing so was to obtain information to help in deciding if they should have a child. Thirty‐four percent of these 836 women entered counseling uncertain about undertaking a pregnancy in the next 2 years. After counseling, 28% of the 836 had uncertain pregnancy intentions. These included 66% of those who were uncertain and 11 % of those who were reproductively certain before counseling. Stepwise logistic regression identified the following as independently and significantly associated with reproductive uncertainty after counseling: 1) uncertainty before counseling; 2) uncertainty about ideal family size; 3) concern about the effects of an affected child on the client's social life; 4) perceived serious problems caring for a child with a birth defect now living at home; and 5) new concerns raised in counseling. Reproductive uncertainty after counseling was not related to characteristics of the risked birth defect, level of risk, treatment potential, or client learning of medical and genetic facts. These data suggest that genetic counseling will not eliminate reproductive uncertainty for many clients, because this uncertainty is related to factors mainly outside the usual scope of counseling.
Factors related to subsequent reproductive outcome in couples with repeated pregnancy loss
Authors: Fitzsimmons Jack , Tunis Sandra , Jackson Douglas , Wapner Ronald J. , Jackson Laird 
Published: June 2005

AbstractSpecific factors in a couple's history may influence the recurrence risk following repeated pregnancy loss (RPL). Couples with RPL were contacted several years following evaluation and information concerning subsequent pregnancies was obtained. Linear regression analysis was utilized to determine which factors in the history were significant predictors of pregnancy outcome following evaluation. A family history of RPL or a “genetic defect” was a highly significant predictor of subsequent unsuccessful pregnancies. Surgical, but not medical, treatment for RPL was a significant predictor of eventual successful outcome. The number of abortions prior to evaluation for RPL, presence of a liveborn child, maternal age at evaluation, and intercurrent infertility all failed to be significant predictors of pregnancy outcome after evaluation.
One hundred twin pregnancies in a prenatal diagnosis program
Authors: Taylor Maida B. , Anderson Robert L. , Golbus Mitchell S. , Opitz John M. 
Published: June 2005

AbstractOne hundred pairs of twins were encountered in 8,500 pregnancies having genetic amniocentesis. Only 5 of 27 (18.5%) pairs were recognized before the institution of routine ultrasonic examination, while 69 of 73 (94%) twin pairs were found after ultrasound use. Amniotic fluid was obtained from both sacs in 71 of the 73 (97%) identified twin gestations in which both twins were living at the time of amniocentesis.
Familial neonatal and infantile seizures: An autosomal‐dominant disorder
Authors: Zonana Jonathan , Silvey Kerry , Strimling Bruce 
Published: June 2005

AbstractFamilial neonatal seizures are an important and probably underrecognized disorder. A family with six affected individuals in three generations was evaluted and their clinical characteristics were compared with those of 15 families previously reported in the literature. An analysis of the 116 affected individuals uncovered a typeical clinical picture of onset of seizures by 2 to 8 days of life in an otherwise healthy appearing infant, and cessation of seizures by 1 to 6 months. Results of diagnostic evaluations were normal, and the pathogenesis of the disorder is still unclear. Long‐term neurodevelopmental outcome was normal except for an increased rate (11%) of subsequent seizures in childhood or as an adult. The disorder was inherited as an autosomal‐dominant trait with a high degree of penetrance.
Some questions on the significance of chromosome alterations in leukemias and lymphomas: A review
Authors: Neri Giovanni , Opitz John M. 
Published: June 2005

AbstractRecent improvement in the methods of chromosome analysis has allowed recognition of consistent chromosome alterations in several human cancers, especially leukemias and lymphomas. At the same time, newly discovered human cellular oncogenes have been mapped to individual chromosomes, with precise band assignment. Some of the assignments are coincident with the breakpoints of translocations observed in particular tumors. In fact, a relocation of the corresponding oncogenes has been observed in the cells of some of these tumors. Two notable examples are that of the t(9;22) translocation of chronic myelogenous leukemia (CML), causing the transfer of the oncogene c‐abl from chromosome 9 to chromosome 22, and that of the t(8;14) translocation of Burkitt lymphoma, causing the transfer of the oncogene c‐myc from chromosome 8 to chromosome 14. These findings can be taken as indicative of a critical role of chromosome alterations in the origin of cancer, through the activation of one or more cellular oncogenes, although there is no firm evidence that such an activation actually occurs. In addition, some concern exists over the validity of accepting in vitro transformation of a cell line by oncogenes as a model of carcinogenesis in man. For these reasons the question on the significance of chromosome alterations in leukemias and lymphomas should not be considered entirely settled yet. Useful models, whose study may lead to the clarification of this important point, are represented by premalignant conditions, such as the myeloproliferative disorders, where chromosome abnormalities are present before the development of a bona fide neoplasm, and by the aneuploidy syndromes, in which there exists an association between a constitutional chromosome anomaly and an increased risk of cancer.
Gross anatomical studies of a newborn infant with the Meckel syndrome
Authors: Pettersen James C. , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractA male infant with the Meckel syndrome was studied anatomically. The findings were compared to those from eight trisomy 13 cases to determine whether or not the superficial similarities between the two syndromes were matched by similarities in the internal variations. Emphasis was on the head and limbs. In the head, major differences were found in the nasal bones, mandible, and tongue. In the limbs, the skeletal variations were more severe in the Meckel syndrome infant, but he lacked the muscle variations diagnostic of trisomy 13.
Genetic counseling in Becker type X‐linked muscular dystrophy. II: Practical considerations
Authors: Grimm T. 
Published: June 2005

AbstractA frequent problem of genetic counseling in Becker muscular dystrophy (BMD) is the differential diagnosis between BMD and the autosomal recessive benign limb‐girdle muscular dystrophy (LGMD) if the pedigree pattern is not typical of X‐linkage. In this situation, the a priori probability that a woman and her husband may be heterozygotes for LGMD can be shown to be 80μ/a (μ = mutation rate in BMD: a = incidence ratio between BMD and LGMD). In addition, the agecorrected serum creatine kinase (CK) values of all female relatives are also important for the risk calculation of a woman being carrier of BMD.
On the statistical determination of major gene mechanisms in continuous human traits: Regressive models
Authors: Bonney George Ebow , Opitz John M. , Reynolds James F. 
Published: June 2005

AbstractWe consider the analysis of a continuous trait measured on human families and pedigrees to elucidate the mechanism of underlying major genes. Thinking in terms of the naturally Markovian structure of the dependencies in pedigrees rather than variance components, we describe natural classes of regressive models that are computationally feasible. These models can accommodate wide generalizations of the residual variation, and so should provide a stronger basis than other models. proposed to date for inferring the segregation and linkage relationships of major genes.