bluuebunny/crossref_metadata_2025_split huggingface dataset:
Preliminary definition of a “critical region” of chromosome 13 in q32: Report of 14 cases with 13q deletions and review of the literature
Authors: Brown Stephen , Gersen Steven , Anyane‐Yeboa Kwame , Warburton Dorothy 
Published: June 2005

AbstractWe report on 14 patients with partial deletions of chromosome 13q. These patients exhibit a wide spectrum of phenotypes. Deletions limited to proximal bands q13–q31 are associated with growth retardation but not with major malformations. We review the literature since 1975 and summarize 13q deletion cases which have a phenotype involving one or more major malformations and mental retardation. Analysis of the breakpoints of these cases, as well as those reported by us, supports the hypothesis that only deletions involving at least part of band q32 are associated with major malformations and digital abnormalities. Patients with more distal deletions have severe mental retardation but do not have major malformations or growth retardation. A group of patients in whom the breakpoint is stated to be within q32 has had an intermediate phenotype. This suggests that it may be possible to define subregions within q32 whose deletion is associated with particular developmental defects. © 1993 Wiley‐Liss, Inc.
Congenital defects of lower limbs and associated malformations: A population based study
Authors: Froster Ursula G. , Baird Patricia A. 
Published: June 2005

AbstractAs part of a detailed study of limb defects and associated patterns of congenital malformations, cases with lower limb deficiencies were analysed separately. We identified a total of 130 cases with deficiencies of the lower limbs without defects of the upper limbs. This gives an incidence of 1.07/10,000 livebirths, or 1/9,337 for this group of limb defects. Most common were femur deficiencies and deficiencies of the foot. A preponderance of males was found in the group of transverse defects of the leg (fibula/tibia deficiencies) and central axis deficiencies, while females had significantly more often longitudinal tibia defects and preaxial ray defects. © 1993 Wiley‐Liss, Inc.
Thermal stability and folding of the collagen triple helix and the effects of mutations in osteogenesis imperfecta on the triple helix of type I collagen
Authors: Bächinger Hans Peter , Morris Nicholas P. , Davis Janice M. 
Published: June 2005

AbstractOsteogenesis imperfecta (OI) is an inherited disease in which 90% of the cases result from mutations in the 2 genes, proα1 and proα2, coding for type I collagen. Type I collagen is a trimeric molecule, (α1)2α2, which is dominated both structurally and functionally by the 300 nm triple‐helical domain. Most OI mutations occur in this domain and almost all point mutations result in the substitution of other amino acids for the obligate glycine which occurs at every third residue. The phenotypic effects of these mutations are frequently attributed in part to alterations in the stability and rate of folding of the triple helix. In order to better understand the relationship between glycine substituions and stability we review current concepts of the forces governing triple helical stability, denaturational and predenaturational unfolding, and the techniques of measuring stability. From observations on the stability of several collagen types as well as synthetic tripeptides, we present a model for stability based on the contribution of individual and neighboring tripeptide units to the local stability. Although in preliminary form, this empirical model can account for the observed shifts in the Tm of many of the point mutations described. The folding of the triple helix is reviewed. The involvement of peptidyl prolyl cis‐trans isomerase in this process in vivo is demonstrated by the inhibition of collagen folding in fibroblasts by cyclosporin A. An hypothesis based on the relationship between the thermal stability at the site of mutation and the propensity for renucleation of folding is proposed.
Formation of mineralized nodules by bone derived cells in vitro: A model of bone formation?
Authors: Beresford Jon N. , Graves Steven E. , Smoothy Caroline A. 
Published: June 2005

AbstractThe identification of the factors which regulate the proliferation and differentiation of cells of the osteoblast lineage remains one of the major challenges in the field of bone cell biology. Although considerable progress has been made in the isolation and culture of cells of the osteoblast lineage from both animal and, more recently, human bone, uncertainties have persisted as to the extent to which these cell populations retain the ability to differentiate into functional osteoblasts in vitro.The formation in vitro of mineralized nodules that exhibit the morphological, ultrastructural and biochemical characteristics of embryonic/woven bone formed in vivo, represents the first evidence that the differentiation of functional osteoblasts can occur in cultures of isolated animal bone‐derived cell populations. It is clear, however, that the culture conditions employed at present only permit a small number of cells to differentiate to the extent of being capable of organising their extracellular matrix into a structure that resembles that of bone. Moreover, it has generally been found that the reproducible mineralization of this extracellular matrix requires supplementation of the culture medium with mM concentrations of β‐GP, which raises doubts as to the physiological relevance of this process.The formation of nodules has also been observed in cultures of human bone‐derived cells. As found in cultures of animal bonederived cells, reproducible mineralization of these nodules will occur in the presence of β‐GP. We have shown, however, that in the presence of the long acting ascorbate analogue Asc‐2‐P, the formation and mineralization of nodules can occur in the absence of β‐GP. The nodules formed in human bone‐derived cell cultures have yet to be characterized as rigorously as those formed in cultures of animal bone‐derived cells and thus it remains to be shown that they resemble bone formed in vivo.
Linkage analysis in dominantly inherited osteogenesis imperfecta
Authors: Sykes Bryan 
Published: June 2005

AbstractThe only serious attempts at linkage in osteogenesis imperfecta (OI) have shown that the disease is linked to type 1 collagen genes in all families studied in which it segregrates as a clear mendelian dominant trait. For prenatal diagnosis the probability that a new family is linked can be taken as greater than 0.95 and this figure is augmented as more meioses are studied. Some phenotype correlations, notably between the OI type IV phenotype and linkage to COL1A2 and between presenile hearing loss in OI type I and linkage to COL1A1, can be used to improve risk estimates substantially in families where there are no segregation data to distinguish whether COL1A1 or COL1A2 is the mutant locus.
Molecular heterogeneity in osteogenesis imperfecta type I
Authors: Willing Marcia C. , Pruchno Charles J. , Byers Peter H. 
Published: June 2005

AbstractOsteogenesis imperfecta (OI) type I is characterized by bone fragility without significant deformity, osteopenia, normal stature, blue sclerae, and autosomal dominant inheritance. Dermal fibroblasts from most affected individuals produce about half the expected amount of type I collagen, suggesting that the OI type I phenotype results from a variety of mutations which alter the apparent expression of either COL1A1 or COL1A2, the genes encoding the chains of type I collagen. Short‐pulse labeling of dermal fibroblasts with [3H]proline from affected individuals in 19 families indicates that most have alterations in the expected 2:1 synthetic ratio of proα1(I): proα2(I), with most having decreased production of proα1(I). Ratios of COL1A1:COL1A2 mRNA from these individuals, using slot‐blot hybridization, indicate that they fall into different groups, but that most have decreased COL1A1 mRNA levels, compared with controls. These data suggest that most of our OI I families have COL1A1 mutations. Copy number and size of the COL1A1 gene by restriction endonuclease analysis of genomic DNA from affected individuals are normal in the families examined. We have identified one 3 generation family in which all affected members have one normal COL1A1 allele and another with a 5 base‐pair deletion near the 3′ end of the gene. The deletion creates a shift in the translational reading‐frame and predicts the synthesis of an elongated proα1(I) chain. In a second family, a father and a son have a single exon deletion that results from a splicing mutation. Chemical cleavage analysis of amplified cDNA from affected individuals in different regions of the COL1A1 gene, including the promoter, suggests that several individuals have point mutations within the coding region of the gene, while one individual may have a small deletion within the α1(I) carboxyl‐terminal propeptide region. Our data provide evidence for significant molecular heterogeneity within the OI type I phenotype and indicate that a variety of mutations can result in decreased synthesis of type I collagen.
Possible role of overglycosylation in the type I collagen triple helical domain in the molecular pathogenesis of osteogenesis imperfecta
Authors: Tenni Ruggero , Valli Maurizia , Rossi Antonio , Cetta Giuseppe 
Published: June 2005

AbstractThe underlying defect in patients affected by a form of osteogenesis imperfecta (OI) clarified at the molecular level regards the amount or the structure of type I collagen synthesized. This leads to a decreased and/or abnormal mineral deposition in bone and affects bone mass and/or strength. Abnormal interactions between collagen molecules in the presence of mutant trimers could give rise to abnormal fibrils, which, in turn, can determine incorrect interactions with noncollagenous matrix macromolecules. The interactious can be disturbed or modulated by an abnormal distribution on the collagen fibril surface of electrically charged or hydrophobic groups, or by an increased presence of sugar moieties linked to hydroxylysyl residues due to chain post‐translational overmodifications (lysyl overhydroxylation and hydroxylysyl over‐glycosylation) of the portion of the triple helical domain of abnormal type I collagen molecules N‐terminal with respect to the defect localization.
Evaluation of growth hormone axis and responsiveness to growth stimulation of short children with osteogenesis imperfecta
Authors: Marini Joan C. , Bordenick Stephanie , Heavner Gale , Rose Susan , Chrousos George P. 
Published: June 2005

AbstractGrowth deficiency is a cardinal manifestation of severe Osteogenesis Imperfecta (OI) and occurs frequently in moderate to mild OI. We have investigated the status of the hormones related to growth in 28 children with OI. Our goals were to determine whether there were any abnormalities of these hormones, whether the abnormalities correlated with types of OI, and whether OI bone could be safely stimulated to grow. The study group included 14 females and 14 males. Using the criteria developed by Sillence et al. [1979], 13 children had OI type III, 12 had OI type IV, and 3 had OI type I. Evaluation included 3 standard hGH provocative tests (AITT, L‐Dopa), GRF stimulation, 24 hr q20 minute sampling of unstimulated growth hormone, and a somatomedin generation test. All patients except one had normal responses to standard provocative stimuli. Responses to GRF fell into 2 groups: one with a mean response similar to that of normal children, and one with a mean response resembling that of GH deficient children. The group with low response to GRF had a significantly lower area under the curve in the 24‐hr test of unstimulated GH than did the normal response group. The OI children as a group showed a blunted IGF‐1 response during the Somatomedin Generation Test, with 18/28 children having less than a two‐fold stimulation. No test results correlated with OI type.Ten OI children were enrolled in a pilot growth stimulation study. Two children received protropin and 8 received clonidine for at least 6 months. Both children treated with protropin and 4/8 treated with clonidine experienced at least a doubling of their pre‐treatment growth rates. Lack of growth hormone response did not correlate with type of OI or parameters from the hormonal evaluation. We speculate that there is a group of OI children who have a hypoactive growth hormone axis. Some OI bone appears to respond to GH and a treatment trial with protropin is planned for a larger number of children.
Marden‐Walker phenotype: Spectrum of variability in three infants
Authors: Ramer Jeanette C. , Frankel Carl A. , Ladda Roger L. 
Published: June 2005

AbstractThe physical, radiographic, and pathologic findings in 3 new patients with Marden‐Walker syndrome (MWS) are compared with those of previously described children with the syndrome. Over 75% of the children with MWS have blepharophimosis, psychomotor retardation, small mouth, micrognathia, kyphosis/scoliosis, and multiple contractures. Minimal diagnostic criteria have yet to be defined attesting to the broad range of variability and potential genetic heterogeneity in this disorder. © 1993 Wiley‐Liss, Inc.
Phocomelia, oligodactyly, and acrania: The Schinzel‐Phocomelia syndrome
Authors: Chitayat David , Stalker Heater J. , Vekemans Michel , Delneste Danielle , Azouz E. Michel 
Published: June 2005

AbstractWe report on a girl born with phocomelia of both lower limbs, with 3‐toed feet and partial sacral agenesis. She had normal growth of the upper limbs and trunk, and normal intelligence. Ultrasound study performed during the subsequent pregnancy documented a large skull defect with an intact brain. Fetal autopsy following the termination of that pregnancy was not done. We think this is a further report of the phocomelia syndrome with additional anomalies as reported by Schinzel [Hum Genet 84:539–541, 1990]. © 1993 Wiley‐Liss, Inc.
Confirmation that the velo‐cardio‐facial syndrome is associated with haplo‐insufficiency of genes at chromosome 22q11
Authors: Kelly David , Goldberg Rosalie , Wilson David , Lindsay Elizabeth , Carey Alisoun , Goodship Judith , Burn John , Cross Ian , Shprintzen Robert J. , Scambler Peter J. 
Published: June 2005

AbstractThe velo‐carido‐facial syndrome (VCFS) and DiGeorge sequence (DGS) have many similar phenotypic characteristics, suggesting that in some cases they share a common cause. DGS is known to be associated with monosomy for a region of chromosome 22q11, and DNA probes have been shown to detect these deletions even in patients with apparently normal chromosomes. Twelve patients with VCFS were examined and monsomy for a region of 22q11 was found in all patients. The DNA probes used in this study could not distinguish the VCFS locus and the DGS locus, indicating that the genes involved in these haplo‐insufficiencies are closely linked, and may be identical. The phenotypic variation of expression in VCFS and DGS may indicate that patients without the full spectrum of VCFS abnormalities but with some manifestations of the disorder may also have 22q11 deletions. © 1993 Wiley‐Liss, Inc.
Exclusion of type II and type VI procollagen gene mutations in a five‐generation family with multiple epiphyseal dysplasia
Authors: Weaver Eric J. , Summerville Gregg P. , Yeh George , Hervada‐Page Maria , Oehlmann Ralph , Rothman Richard , Jimenez Sergio A. , Knowlton Robert G. 
Published: June 2005

AbstractWe have studied a family with an autosomal dominant form of multiple epiphyseal dysplasia (MED) inherited through at least 5 generations. Bilateral deformity of the hips with subsequent degenerative arthritis was the most common and most severe change observed in the affected relatives. Abnormalities of the knees, ankles, and shoulders were also noted in some affected individuals. Radiological examination showed changes in affected joints consistent with epiphyseal dysplasia. In early stages, the articular surfaces appeared flattened or irregular in shape. In advanced stages, epiphyseal fragmentation, joint surface erosion, and extensive remodeling were observed.The abnormalities of the epiphyses suggested that the primary defect might be in a structural component of the epiphyseal cartilage matrix. The gene encoding type II collagen (COL2A1) was tested for genetic linkage to MED in this family by restriction fragment length polymorphism (RFLP) analysis. Recombination between COL2A1 and MED was observed, ruling out COL2A1 as the site of the mutation. The genes encoding the 3 chains of type VI collagen were also excluded on the basis of discordant inheritance. The disease in this family is therefore not the result of mutations in the genes encoding type II or type VI collagen. © 1993 Wiley‐Liss, Inc.
Axial mesodermal dysplasia spectrum
Authors: Stewart Fiona J. , Nevin Norman C. , Brown Stephen 
Published: June 2005

AbstractWe report on a 4‐month‐old boy with manifestations of both the oculo‐auriculovertebral spectrum and the caudal regression sequence. He has preauricular appendages, thoracic and lumbar hemivertebrae, anomalies of the ribs, dextrocardia, sacral “dysplasia”, dislocated hips, bilateral talipes equinovarus, imperforate anus, recto‐vesical fistula, malformed scrotum, and undescended testes. As suggested by Russell et al. [1981], who reported a patient with similar anomalies, the spectrum of anomalies probably is due to a generalized alteration in mesodermal cell migration during the primitive streak period. The term “axial mesodermal dysplasia spectrum” best describes the widespread anomalies in the cranial and caudal regions. © 1993 Wiley‐Liss, Inc.
Tricho‐rhino‐phalangeal syndrome type I (TRP I) due to an apparently balanced translocation involving 8q24
Authors: Marchau Fabienne E. , Van Roy Bernadette C. , Parizel Paul M. , Lambert Julien R. , De Canck Ilse , Leroy Jules G. , Gevaert Carine M. , Willems Patrick J. , Dumon Jan E. 
Published: June 2005

AbstractTricho‐rhino‐phalangeal (TRP) syndromes type I and II are caused by a defective gene located on chromosome 8q24.1. We report a family with 2 sibs affected with TRP type I in combination with an apparently balanced chromosome (8;18) translocation involving 8q24.11. It is very likely that the 8q24 translocation breakpoint is physically linked to the TRP gene(s), thereby facilitating future efforts to clone the TRP gene(s). © 1993 Wiley‐Liss, Inc.
Protein‐losing gastroenteropathy with facial anomaly and growth retardation: A mild case of Hennekam syndrome
Authors: Yasunaga Michiho , Yamanaka Chutaro , Mayumi Mitsufumi , Momoi Tohru , Mikawa Haruki 
Published: June 2005

AbstractA 7‐year‐old boy with a peculiar face, protein‐losing gastroenteropathy and growth retardation is reported. Although he has a face similar to those 5 cases reported previously by Hennekam et al. (Am J Med Genet 34:593–600, 1989) and Gabrielli et al. (Am J Med Genet 40:244–247, 1991), he is not mentally retarded nor does he have severe lymphedema. This patient seems to have a mild case of the Hennekam syndrome. © 1993 Wiley‐Liss, Inc.
Kallmann syndrome associated with complex chromosome rearrangement
Authors: Casamassima Anthony C. , Wilmot Patrick L. , Vibert Betsy K. , Shapiro Lawrence R. 
Published: June 2005

AbstractWe report on a male with Kallmann syndrome (KS) and an apparently balanced complex chromosome rearrangement (CCR): 46,XY,t(3;9)(9;12)(q13.2;q21.2p13;q15). This is the first known report of a CCR in the KS and the second reported case of a definitive autosomal chromosome abnormality with KS. Possible relationships between the cytogenetic abnormality and KS are discussed. © 1993 Wiley‐Liss, Inc.
Spastic paraplegia, epilepsy, and mental retardation in several members of a family: A novel genetic disorder
Authors: Gigli G. L. , Diomedi M. , Bernardi G. , Placidi F. , Marciani M. G. , Calia E. , Maschio M. C. E. , Neri G. 
Published: June 2005

AbstractWe report on a family in which an association between spastic paraplegia and epilepsy has been observed.This disorder is an autosomal dominant trait with incomplete penetrance and variable expressivity. The onset was limited to the first four decades of life; the symptoms were typically those of progressive weakness and spasticity of lower limbs. Epilepsy was present in members of three of the four generations on whom we have information.The concomitance of spastic paraplegia and epilepsy in several members of the same family is unlikely to be fortuitous and probably represents the pleiotropic effect of a single mutant gene. © 1993 Wiley‐Liss, Inc.
Balanced reciprocal translocation mosaicism associated with an abnormal phenotype
Authors: Aughton David J. , AlSaadi Abdul A. , Canady Alexa I. , Lucas Barbara M. 
Published: June 2005

AbstractBalanced reciprocal translocation mosaicism is rarely reported in humans. Only two previous cases have been associated with an abnormal phenotype. We report on a third case of apparently balanced reciprocal translocation mosaicism associated with an abnormal phenotype, largely different from those reported previously. Since low levels of mosaicism may not be detected in routine cytogenetic analyses, balanced reciprocal translocation mosaicism may be associated with an abnormal phenotype more often than has been recognized to date. © 1993 Wiley‐Liss, Inc.
Concurrence of supravalvular aortic stenosis and peripheral pulmonary stenosis in three generations of a family: A form of arterial dysplasia
Authors: Kumar Anil , Stalker Heather J. , Williams Charles A. 
Published: June 2005

AbstractIsolated supravalvular aortic stenosis (SVAS) commonly is an autosomal dominant trait; it may also occur in the Williams syndrome (WS). While peripheral pulmonary stenosis (PPS) can occur in the same individual with familial isolated SVAS, concurrence of these lesions in different relatives of a family is uncommon. We describe five affected individuals in one family; three had isolated SVAS, one had isolated PPS, and one had SVAS and PPS. Based on this family and review of literature, we suggest that SVAS is a form of arterial dysplasia encompassing PPS in its spectrum. It is developmentally distinct from other left heart obstructive lesions that are hypothesized to be related to blood flow abnormalities in the developing embryo. We also conclude that the clinical disorder in this family represents one that is distinct from WS. © 1993 Wiley‐Liss, Inc.
Cranial nerve abnormalities in CHARGE association
Authors: Byerly Kyna A. , Pauli Richard M. 
Published: June 2005

AbstractMany children with the CHARGE association have facial paralysis and feeding and swallowing difficulties. Indeed, facial paralysis and pharyngeal incoordination may be important diagnostic indicators of CHARGE association [Davenport et al., 1986a; Mitchell et al., 1985]. We describe an individual with dysfunction of multiple cranial nerves (Möbius sequence) and CHARGE association, a previously unrecognized combination. Our review of 150 patients from the literature and 13 patients from this center with CHARGE association documented that dysfunction of cranial nerves is frequent in CHARGE association, and that often cranial nerve abnormalities are multiple. Such multiple cranial nerve abnormalities may be the primary underlying cause for the facial paralysis, feeding difficulties and sensorineural hearing loss seen in many individuals with CHARGE association. © 1993 Wiley‐Liss, Inc.