bluuebunny/crossref_metadata_2025_split huggingface dataset:
The nasopalpebral lipoma‐coloboma syndrome: A new autosomal dominant dysplasia‐malformation syndrome with congenital nasopalpebral lipomas, eyelid colobomas, telecanthus, and maxillary hypoplasia
Authors: Penchaszadeh Victor B. , Velasquez Darlin , Arrivillaga Ramon , Opitz John M. 
Published: June 2005

AbstractWe describe a new autosomal dominant dysplasia‐malformation syndrome from eight affected individuals in three generations of a Venezuelan family. It is characterized by congenital symmetrical upper lid and nasopalpebral lipomas, bilateral symmetrical upper and lower palpebral colobomas located at the junction of the inner and middle thirds of the lids, telecanthus, and maxillary hypoplasia. Affected individuals have a broad forehead, widow's peak, abnormal pattern of eyebrows and eyelashes, and maldevelopment of the lacrimal punctae. Interorbital distance is normal, but interpupillary distance is increased due to divergent strabismus originating from visual interference from inner canthal masses. Persistent epiphora, conjunctival hyperemia, and corneal (and less frequently lens) opacities are a secondary consequence of the defect of the lacrimal punctae and the inability to close the lids completely. The syndrome has complete penetrance and a rather narrow range of expressivity. The primary defect could involve a dysplasia of adipose tissue leading to nasopalpebral and upper lid lipomas during embryogenesis, with the rest of the malformations being secondary to interference of morphogenesis of the mid‐upperface developmental field from the lipomatous hamartomas. Alternatively, a central rather than a peripheral mechanism of malformation might be considered, such as defective migration of neural crest cells.
Occurrence of cyclopia, myelomeningocele, deafness, and abducens paralysis in siblings
Authors: Burck Uta , Held Karsten R. , Kitschke Hans‐J. , Opitz John M. 
Published: June 2005

AbstractAs holoprosencephaly without chromosome defect may be associated with other CNS‐related anomalies such as mental retardation, mental illness, facial paralysis, endocrine disorders, deafness, spina bifida, and myelomeningocele, we present a family in which one girl had a myelomeningocele, a brother had orbital hypotelorism, facial and cerebral asymmetries, cerebral palsy, abducens paralysis, and inner ear deafness. A 3rd pregnancy was terminated at 16 weeks; the fetus had cyclopia. A common cause is discussed in these cases and in those families in which holoprosencephaly and additional malformations occur among different generations.
The fragile X chromosome: Current methods
Authors: Hecht Frederick , Jacky Peter B. , Sutherland Grant R. 
Published: June 2005

AbstractAt the International Congress of Human Genetics (Jerusalem, September, 1981) a Workshop was held on the fragile X chromosome; it was entitled “The Fragile X Chromosome: Current Methods.” It was to focus on laboratory methods required to detect or to enhance the detection of the fragile X.The fragile site on the X chromosome is one of 13 proven fragile sites known in humans. (A diagram of these sites is provided.) The fragile site on the X is sensitive to the concentration of folic acid in the medium in which cells are cultured. Cytologically, gaps and breaks are increased at the X fragile site, which is located at band Xq27–28. To enhance expression in lymphocytes, prolongation of culture time to 96 hours, elevation of the pH, diminution of the colcemid effect, and air drying of slides are helpful. The need for methionine in low‐folate media can be overridden by the addition of fluorodeoxyuridine (FUdR). Detection of the fragile X in males requires meticulous attention to methods of lymphocyte culture and metaphase preparation and then the examination of a sufficient number of mitoses, eg, 50–100 metaphases per individual. Detection of the fragile X in female carriers is often more difficult. Uniform detection of all obligate female carriers has not been achieved. Difficulty may correlate with increasing age or intelligence of females.Key methodologic advances with the fragile X include the addition of methotrexate, trifluorothymidine or, especially of FUdR to the culture medium. FUdR, for example, is helpful in demonstrating the fragile X in lymphoblastoid cell lines and fibroblasts. Both of these cell types now represent an opportunity to study the biochemistry of the fragile X.The success of the FUdR technique with skin fibroblasts heralds the feasibility of demonstrating the fragile X chromosome in cultured amniocytes. Since the Workshop, it has been reported that with FUdR the fragile X could in fact be detected in 46,XY amniotic fluid cells.
Studies of microcephalic primordial dwarfism I: Approach to a delineation of the seckel syndrome
Authors: Majewski F. , Goecke T. , Opitz John M. 
Published: June 2005

AbstractThe literature dealing with the Seckel syndrome is discussed critically. Some 60 patients have been published as having the Seckel syndrome. The diagnostic criteria proposed by Seckel are met by only 1/3 of these. It seems evident that this “syndrome” is a heterogeneous group of microcephalic primordial dwarfism. An approach to the delineation of the Seckel syndrome is given.
Studies of microcephalic primordial dwarfism III: An intrauterine dwarf with platyspondyly and anomalies of pelvis and clavicles—osteodysplastic primordial dwarfism type III
Authors: Majewski F. , Stoeckenius M. , Kemperdick H. , Opitz John M. 
Published: June 2005

AbstractWe report a male infant with intrauterine growth retardation (IUGR) with alopecia, microcephaly, receding forehead and chin, large eyes, and large prominent nose. Roentgenographic examination showed platyspondyly, “dysplasia” of pelvis, elongated clavicles, and enlargement of proximal femora, clearly separating this condition from all presently known types of microcephalic IUGR.
Ring chromosome 6: Case report and review
Authors: Nishi Yoshikazu , Yoshimura Osamu , Ohama Koso , Usui Tomofusa , Opitz John M. 
Published: June 2005

AbstractA ring chromosome 6 was identified in an apparently healthy girl with short stature and microcephaly. Of 100 peripheral lymphocyte metaphases analyzed, chromosome 6 was replaced in 73% by a monocentric ring chromosome, in 10% by a dicentric, in 1% by a tricentric, and 3% by two rings. Thirteen other cells were 45,XX, −6, which may represent 46,XX,r(6)/45,XX, −6 mosaicism. The breakpoints were located on bands p24 or p25 and q26 or q27. Eight other patients with a ring chromosome 6 have been reported. The most characteristic findings in subjects with a ring chromosome 6 are mental retardation and eye and ear abonormalities, none of which were present in our patient.
The implications of S‐phase exchanges for the mechanisms of radiosensitivity in trisomy 21
Authors: Athanasiou K. , Bartsocas C. S. , Opitz John M. 
Published: June 2005

AbstractHuman lymphocytes obtained from four patients with Down syndrome and from two normal individuals were irradiated with X‐rays during their S phase and examined for chromatid type aberrations. It is suggested that the significantly increased frequency of asymmetrical chromatid interchanges found in trisomic cells is related to an altered DNA repair system. This altered repair system is probably responsible for the increased frequency of chromosome aberrations that can be induced in these cells by x‐rays and the increased tendency for leukemia observed in Down syndrome as well.
The role of Yp in sex determination: New evidence from X/Y translocations
Authors: Zuffardi Orsetta , Maraschio Paola , Lo Curto Franco , Müller Ulrich , Giarola Arturo , Perotti Lisa , Opitz John M. 
Published: June 2005

AbstractA 33‐year‐old man had azoospermia and tubular atrophy as in the Klinefelter syndrome but short stature. He had a 46,X,t(X/Y) (Xqter→p22.3::Yp11→Yqter) translocation and was H‐Y antigen‐positive. This excludes one of the genes controlling H‐Y antigen from the terminal portion of the short arm of the Y chromosome. This case and the two similar ones in the literature indicate that the proximal Yp portion is required for the differentiation of a male gonad. The pattern of X inactivation was random in the patient's fibroblasts, whereas in the lymphocytes the translocated chromosome was preferentially inactivated; comparison with other cases shows that the quantity of Y chromosome material involved in these translocations does not influence the X inactivation patterns. In the three cases with this dicentric translocation the X chromosome centromere is consistently the active one. Our case indicates that the choice of which centromere is inactivated is independent of the replication pattern of the X chromosome. Our patient and a few other relevant cases from the literature confirm that factors controlling height are located on the distal portion of Xp and of Yp.
The effects of long‐term fetal constraint in vitro on the cranial base and other skeletal components
Authors: Jaskoll Tina , Melnick Michael 
Published: June 2005

AbstractRecently it was suggested that some cases of premature closure of the sagittal suture in humans may be due to fetal head constraint. Using various modifications of the procedure for long‐term shell‐less cultivation of chick embryos, we sought to test the hypothesis that fetal head constraint may result in abnormalities of the cranial base and other skeletal structures of the head. Our experiments with various sized containers demonstrate that fetal constraint is associated with both deformation and malformation of the craniofacial skeleton, including the cranial base, squamosal, columella (stapes), and mandible. The severity of both deformation and malformation appears to be a function of the degree of fetal constraint. If, as some suggest, abnormality of the cranial base is the primary anomaly in craniosynostosis, then our results tend to support the fetal constraint hypothesis as one explanation of simple craniostenosis.
Power of the affected‐sib‐pair method to detect disease susceptibility loci of small effect: An application to multiple sclerosis
Authors: Suarez Brian , O'Rourke Dennis , Van Eerdewegh Paul , Opitz John M. 
Published: June 2005

AbstractThe distribution of marker locus identity‐by‐descent scores in affected sib pairs provides a powerful tool for detecting the presence of a linked non‐Mendelian disease susceptibility locus. This basic approach is here extended to include a trio of sibs. A special type of sib trio consisting of two affected and one unaffected sib is investigated. It is shown that compared to affected‐sib‐pairs, trios with the above configuration are less efficient in detecting the presence of a linked disease susceptibility locus.When the generalized two‐allele single locus model is fitted to sib pairs affected with multiple sclerosis, an estimate of the recombination fraction of 0.21 between the putative disease susceptibility locus and the HLA complex is obtained. However, this transmission model is deemed inadequate since a recombination fraction this large is inconsistent with the variety of HLA associations observed at the population level.
Not all cystic hygromas occur in the Ullrich‐Turner syndrome
Authors: Cowchock F. Susan , Wapner Ronald J. , Kurtz Alfred , Chatzkel Sherrie , Barnhart Jay S. , Lesnick Dianna C. , Opitz John M. 
Published: June 2005

AbstractWe report two sib fetuses with nuchal systic hygroma and cleft palate. This condition is probably recessively inherited as the parents have normal chromosomes (G‐banded) and the fetuses were of opposite sex. Nuchal cystic hygroma is a nonspecific malformation, which reflects a delay in development of the connection between the jugular lymph sacs and the internal jugular vein. This fetal malformation and its equivalent in the adult, neck webbing, has been reported to be a part of a variety of genetic malformation syndromes. Some suggestions for counseling parents of an affected fetus are made: If the chromosome karyotype of an affected fetus is unknown, ultrasound examination, rather than AFP studies, is suggested for future pregnancies.
Sacroiliitis in the old order Amish
Authors: Arnett Frank C. , Enlow Roger W. , Bias Wilma B. , Opitz John M. 
Published: June 2005

AbstractIn a study designed to clarify the relationship of HLA‐B27 and sacroiliitis, 45 members of seven Old Order Amish families were thoroughly evaluated for sacroiliitis. The primary study group was three sibs who carried HLA‐B27 and three of their other sibs who inherited the alternate non‐B27 haplotype, their spouses and offspring. The seventh B27 positive family was more distantly related. The study was undertaken with no prior knowledge of disease in these families. These families represented all the B27‐positive subjects who had been ascertained up to the time the study began. In these selected families, 24% of the members were found to have sacroiliitis, irrespective of whether they were B27 positive. Analysis of the relevance of HLA to disease in this kindred was confounded by the presence of Bw39 and B17, antigens associated with psoriatic arthritis. However, not all B27‐negative cases possessed one or both of these specificities. Rather than clarifying the relationship of B27 to disease, this study, in a highly consanguineous kindred, indicated that other nonlinked loci may be epistatic to B27, that other HLA alleles may be involved, or that certain causes are more prevalent in the Amish than in the non‐Amish population.
Does unequal crossing over contribute to the mutation rate in Duchenne muscular dystrophy?
Authors: Winter R. M. , Pembrey M. E. , Opitz John M. 
Published: June 2005

AbstractIn order to explain the high mutation rate in Duchenne muscular dystrophy (DMD), together with the apparent equal incidence of new mutations in sperms and ova, which is unusual when compared with other X‐linked conditions, it is postulated that a significant proportion of new mutations in DMD are caused by unequal crossing over in females at meiosis. If this is true, then there are important consequences for the strategy of research into the molecular basis of DMD.
A five‐generation family with sacral agenesis and spina bifida: Possible similarities with the mouse T‐locus
Authors: Fellous M. , Boué J. , Malbrunot C. , Wollman E. , Sasportes M. , Van Cong N. , Marcelli A. , Rebourcet R. , Hubert Ch. , Demenais F. , Elston R. C. , Namboodiri K. K. , Kaplan E. B. , Fellous M. , Opitz John M. 
Published: June 2005

AbstractIn man, a malformation that recalls some of the defects associated with T/t mutants in the mouse is sacral agenesis. We report on a family with a high incidence of sacral malformation, ranging from a complete absence of the sacrum (SA), with or without spina bifida aperta, to a spina bifida occulta (SBO) that could only be detected by x‐ray. The condition appeared in a man with four children who were all affected, and thereafter, to varying degrees, in 17 of his 28 descendants.Segregation analysis has been performed in this family, using the Elston and Stewart transmission probability model [1971]. The two traits (SA and SBO) were first studied separately and then together. A fully penetrant major dominant gene is shown to cause SA. When the phenotypes SA and SBO are considered together, Mendelian transmission is rejected. This could be explained genetically by two alternative hypotheses: genetic heterogeneity or a dominant major gene transmitted in excess by heterozygotes (τAa A = 0.896), suggesting a segregation distortion property of an allele at a T‐like locus.In the mouse, the T‐locus is linked to the major histocompatibility complex H‐2. Thus linkage was investigated between this assumed major SA gene and five polymorphic markers, especially those located on chromosome 6 (PGM3 and HLA). When SA is studied, none of the lod scores are significant. However, when SA + SBO are examined together a high lod score is obtained with PGM3 under the hypothesis of no sporadic cases (lod score = 1.85 at a recombination fraction of 0.087 ± 0.084).Although similarities with a T‐locus (segregarion distortion, possible linkage with PGM3) appear in this pedigree, genetic heterogeneity of SA cannot be excluded.
Duchenne muscular dystrophy carrier detection using logistic discrimination: Serum creatine kinase, hemopexin, pyruvate kinase, and lactate dehydrogenase in combination
Authors: Percy Maire E. , Andrews David F. , Thompson Margaret W. 
Published: June 2005

AbstractIn the absence of an unambiguous test for identifying Duchenne muscular dystrophy (DMD) heterozygotes, methods are needed for combination of the results of individually equivocal tests as effectively and rationally as possible. We used logistic discrimination to assess the effectiveness of measurements of serum creatine kinase, hemopexin, pyruvate kinase, and lactate dehydrogenase alone and in various combinations in identifying DMD carriers. We analyzed 127 serum samples from 63 normal female controls (20–40 years old) and 67 from 38 obligate DMD carriers. The best two tests to use in combination were creatine kinase and hemopexin, and these two, with lactate dehydrogenase, were the best three. Use of all four tests was significantly better than any two or three. At the 95% level (with 5% of controls misclassified), 54% of the carriers were identified by CK alone, whereas 88% were identified by means of the four tests. Although a small proportion of known carriers still cannot be identified, application of the four tests to a group of 45 possible carrier mothers of isolated cases of DMD resolves the population into fairly discrete “normal” and “abnormal” subgroups. Thus, if bias of selection can be eliminated, application of logistic discrimination may permit a direct estimate of the proportion of mothers of affectecd boys who are homozygous normal.
A lethal, larsen‐like multiple joint dislocation syndrome
Authors: Chen Harold , Chang Chung‐Ho , Perrin Eugene , Perrin Jane , Opitz John M. 
Published: June 2005

AbstractWe describe here two isolated cases of lethal, Larsen‐like multiple joint dislocation syndrome. Death occurred shortly after birth with pulmonary insufficiency due to tracheomalacia and/or lung hypoplasia. Both had abnormal dermal collagen bundles. In one case, histochemical studies showed abnormal cartilagenous matrix and striking deficiency in the dense collagen bundles of joint capsules; electron‐microscopic studies of the hyalin cartilage of the trachea documented a relative increase of the small, short fibers with decrease of the matrix collagen fibers. This study confirms that this Larsen‐like syndrome is a disorder of connective tissue, possibly involving dysmaturity of the collagen fibers, with a predilection for joint capsules and tracheal cartilage. This lethal condition is characterized by pulmonary insufficiency, tracheomalacia, and collagen fiber dysmaturity.
Theory of genetic counseling for rare recessive traits with consanguinity
Authors: Murphy Edmond A. , Rosell Magdalena I. , Rosell E. Manuel 
Published: June 2005

AbstractThe theory of assessing genetic risk for rare autosomal recessive traits in the face of extensive consanguinity is explored. A general lemma is proved that justifies the partition of posterior probability and recursive incorporation of it, as a means of reducing the logic of analysis to steps of manageable complexity: the conditions are that either the components should be independent or that each component, as it is added, is conditioned on the occurrence of all earlier components. An example is given of a pedigree in which the tracing of a gene by the method of expected proportions is misleading, and another that points up the importance of the posterior information. Four classes of patterns are identified and appropriate methods devised for handling them: the single consanguineous loop, multiple mutually‐external loops, nested loops, and multiple closures. The latter problem may be treated in general by the use of truncated generating functions, with or without the use of matrix methods.
Sib risks for nonspecific mental retardation in British Columbia
Authors: Herbst Diana S. , Baird Patricia A. , Herrmann Jürgen 
Published: June 2005

AbstractCases of nonspecific mental retardation (MR) born in British Columbia between 1952 and 1970 ascertained through the British Columbia Health Surveillance Registry were linked by birth registration number to family sibships from computer‐linked groupings of birth and marriage records in British Columbia. It was possible to retrieve family information for 97% of the cases by this method.Because of good ascertainment and relatively large sample size, the 1952–1965 birth cohort comprising 2,209 index cases was selected for calculations of overall risks and recurrence risks to sibs categorized by sex, MR level, associated neurological disability, and singleton versus multiple birth. The overall risk of affected individuals among all sibs was 4.4 ± 0.6%, which was about ten times greater than the minimum population incidence of nonspecific MR. The risk among subsequent sibs of the first affected case in a family was 3.7 ± 0.8%. These risks varied depending on sex, MR level, and whether the mental retardation was associated with hydrocephalus, microcephalus, cerebral palsy, or epilepsy. The recurrence risk after two affected individuals was 12 ± 7% – about three times greater than after one affected individual. Even though the frequency of MR is greater among twins than in the overall population, the recurrence risk of nonspecific MR was not significantly different for index cases from either singleton or multiple births.
Cockayne syndrome with early onset of manifestations
Authors: Moyer Donna B. , Marquis Paul , Shertzer Mark E. , Burton Barbara K. , Opitz John M. 
Published: June 2005

AbstractThe Cockayne syndrome is an autosomal recessive syndrome of growth failure and characteristic physical and pathological changes. Typically the disorder becomes manifest in the second year of life; growth and development are normal during the first year. We report presumably monozygotic twins with otherwise classic Cockayne syndrome but with a prenatal onset. Several previously described cases seem to represent a similar form of Cockayne syndrome with early onset of growth failure and development delay.
The greig cephalopolysyndactyly syndrome in a canadian family
Authors: Chudley Albert E. , Houston C. Stuart , Opitz John M. 
Published: June 2005

AbstractA father and his son and daughter had preaxial and postaxial polydactyly, syndactyly, and craniofacial changes including macrocephaly and were diagnosed as having the Greig cephalopolysyndactyly syndrome. Additional defects in the father and other reportedly affected relatives were inguinal hernias and camptodactyly.
A clinical syndrome associated with dup(5p)
Authors: Carnevale Alessandra , Hernández Marisela , Limón‐Toledo Irma , Frías Sara , Castillo Julieta , Del Castillo Victoria , Opitz John M. 
Published: June 2005

AbstractWe report two cases of dup(5p), both the consequence of an unbalanced segregation of a balanced translocation. Our cases and those previously published suggest that dup(5p) when involving at least a portion of band 5p13 results in a recognizable clinical syndrome of congenital malformations, mental retardation, and growth failure. Although the size of the trisomic segment is different, the patients have a similar phenotype.
Posterior shoulder girdle abnormalities with absence of pectoralis major muscle
Authors: Hegde H. R. , Shokeir M. H. K. , Opitz John M. 
Published: June 2005

AbstractWe have reviewed 12 consecutively ascertained individuals with unilateral absence of the sterno‐costal head of the pectoralis major muscle and have studied associated abnormalities of the posterior shoulder girdle and their frequency and extent as contrasted with that of the symbrachydactyly. We found certain previously unreported associations of skeletal and renal anomalies in these individuals. We review various speculations regarding the possible causes of the Poland anomaly.