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Biomedical subjects

D L Rimoin

Publications and source records attributed to D L Rimoin.

At least 55 records · Page 3Linked to original sources
PubMed1998

Localization of a multiple synostoses-syndrome disease gene to chromosome 17q21-22.

Multiple synostoses syndrome is an autosomal dominant disorder characterized by premature onset of joint fusions, which initially affect the interphalangeal joints, by characteristic facies, and by deafness. We performed linkage analysis on a large Hawaiian family with multiple synostoses syndrome. Because another autosomal dominant disorder, proximal symphalangism, shares some clinical symptoms with multiple synostoses syndrome and has been linked to markers at loci at chromosome 17q21-22, we tested the hypothesis that multiple synostoses syndrome is linked to the same chromosomal region. Using polymorphic markers from the proximal symphalangism interval, we conducted linkage analysis and showed that the multiple synostoses-syndrome phenotype is linked to the same chromosomal region. A maximum LOD score of 3.98 at recombination fraction of .00 was achieved for the marker at locus D17S787. Further genetic analysis identified individuals with recombinant genotypes, allowing localization of the disease gene within the interval D17S931-D17S792, a 16-cM region. These data provide evidence that multiple synostoses syndrome and proximal symphalangism may be allelic disorders.

Abnormalities, Multiple↗
PubMed1997

Brachydactyly-short stature-hypertension (Bilginturan) syndrome: report on two families.

We report on two families with autosomal dominant brachydactyly of hands and feet and hypertension. All affected members of the first family had proportionate short stature. However, the propositus and the affected relatives in the second family were only short compared to unaffected relatives. The hypertension was medically responsive in all cases. The propositus in the second family had poor compliance and a striking generalized vasculopathy. All patients were of normal intelligence and had a normal facial appearance. The brachydactyly-short stature-hypertension syndrome was first reported by Bilginturan et al. [1973] in a Turkish family and the families reported by us are Caucasian and Hispanic. The gene causing this condition in the original Turkish family was recently mapped to 12p. Our report expands our existing knowledge and the ethnic diversity of this syndrome.

Adult↗
PubMed1997

The Pointer syndrome: a new syndrome with skeletal abnormalities, camptodactyly, facial anomalies, and feeding difficulties.

We describe a brother and sister with a unique combination of skeletal findings including camptodactyly (phalangeal dislocations), facial anomalies, neonatal respiratory problems, and feeding problems due to poor suck. Metaphyseal splaying, osteopenia, endosteal bone apposition, campomelia, and multiple fractures characterize the other skeletal abnormalities. The parents are first cousins once removed and are unaffected. These cases appear to represent a previously undescribed autosomal recessive disorder.

Abnormalities, Multiple↗
PubMed1997

The scapula as a window to the diagnosis of skeletal dysplasias.

Evaluation of the scapula can be useful in the diagnosis of skeletal dysplasias and helpful for the classification and delineation of new entities. A review of 2100 computerized cases of skeletal dysplasias in the International Skeletal Dysplasia Registry was performed. We found that the Luton type of platyspondylic lethal skeletal dysplasia differed radiographically from the San Diego type and Torrance type by the presence of two spikes at the inferior angle of the scapula. Hypoplasia of the body of the scapula, which is characteristic for campomelic dysplasia but not for kyphomelic dysplasia, is also present in Antley-Bixler syndrome. Radiographic and clinical similarities between campomelic dysplasia and Antley-Bixler syndrome suggest that they might be related disorders and that the latter condition should be included in the bent-bone dysplasia group. Similarity between the metaphyseal regions of the scapula and the metaphyses of the long tubular bones in the different types of short-rib polydactyly syndrome illustrates the importance of evaluation of the scapula in this group as well as in other well-defined or unknown osteochondrodysplasias.

Bone Diseases, Developmental↗
PubMed1997

Spondylo-mesomelic-acrodysplasia with joint dislocations and severe combined immunodeficiency: a newly recognised immuno-osseous dysplasia.

A newborn girl is described with an association of spondylo-acrodysplasia, mild short limbed dwarfism without significant metaphyseal changes, joint dislocations, and severe immune system dysfunction. This association is distinct from other known immuno-osseous dysplasias, including Schimke dysplasia, ADA deficiency with osseous changes, and Omenn phenotype with short limbed dwarfism.

Female↗
PubMed1996

Molecular defects in the chondrodysplasias.

There has been a recent explosion of knowledge concerning the biochemical and molecular defects in the skeletal dysplasias. Through both the candidate gene approach and positional cloning, specific gene defects that produce the skeletal dysplasias have been identified and may be classified into several general categories: 1) qualitative or quantitative abnormalities in the structural proteins of cartilage; 2) inborn errors of cartilage metabolism; 3) defects in local regulators of cartilage growth; and 4) systemic defects influencing cartilage development.

Adenosine Deaminase↗
PubMed1996

Multiple vertebral segmentation defects: analysis of 26 new patients and review of the literature.

To further delineate and classify those forms of short trunk dwarfism characterized by multiple vertebral segmentation defects, we analyzed 26 new patients and reviewed 115 described in the literature. Three distinct entities were recognized based on radiographic and clinical findings. Jarcho-Levin syndrome is the lethal autosomal recessive form, characterized by a symmetric crab-like chest. Spondylocostal dysostosis is the benign autosomal dominant condition. Spondylothoracic dysostosis shows considerable clinical and radiographic overlap with spondylocostal dysostosis. Malformations observed in association with multiple vertebral segmentation defects are more common in the sporadic patients. Analysis of the 26 new individuals revealed that the body segment in which these nonvertebral malformations occur corresponds to the site of the vertebral segmentation defects.

Adolescent↗
PubMed1996

Epidemiology of osteochondrodysplasias: changing trends due to advances in prenatal diagnosis.

The osteochondrodysplasias (skeletal dysplasias) are a heterogeneous group of disorders characterized by abnormalities in cartilage and bone growth and development. Some of these disorders are detectable during the second trimester by sonographic techniques. We ascertained cases of osteochondrodysplasias in elective pregnancy terminations, stillborn infants older than 20 gestational weeks, and liveborn infants diagnosed by the fifth day of life as part of an ongoing active malformation surveillance program. Forty-nine cases of osteochondrodysplasias were identified among approximately 126,000 deliveries at Brigham and Women's Hospital (BWH) during a 15-year period (Feb. 16, 1972-Feb. 15, 1975; Jan. 1, 1979-Dec. 31, 1990). When cases delivered to women who had planned to deliver at another hospital but were transferred for high-risk care (transfers) were excluded, the prevalence rate was 2.14 cases per 10,000 deliveries. During the early period (1972-1975) no cases were suspected prenatally, while during the 1988-1990 period, 80% of all cases and 57% of cases delivered to women who had always planned to deliver at BWH (non-transfers) were suspected by ultrasonography. Birth status changed through our period of surveillance. In the final 3-year period (1988-1990), 40% of all cases and 29% of non-transfers with osteochondrodysplasias were pregnancy terminations, compared to none during the 1972-1975 period. The increasing frequency of pregnancy terminations complicated the diagnosis of these conditions. Despite extensive evaluation, a definitive diagnosis was not possible in 8 of 49 cases (16%). Biochemical and molecular genetic methods of diagnosis will continue to become more important if the current trend of wide utilization of prenatal sonography and termination of affected pregnancies continues.

Abortion, Induced↗
PubMed1996

Short-term recombinant human growth hormone treatment increases growth rate in achondroplasia.

To investigate the effect of recombinant hGH treatment on the growth rate and proportion of individuals with achondroplasia and hypochondroplasia, we studied 15 individuals with these common skeletal dysplasias. The study lasted 24 months and included 6 months of observation, 12 months of hGH therapy (0.04 mg/kg.day), and 6 months of posttreatment growth rate determination. In achondroplasia, the mean growth rate during the hGH treatment (5.3 +/- 1.6 cm) was significantly increased compared with that during the pretreatment (4.0 +/- 1.0 cm.yr, P < 0.01)) and posttreatment periods (3.1 +/- 1.3 cm; P < 0.001). In the 4 children with hypochondroplasia, the growth rate during hGH treatment was 7.0 +/- 2.4 cm/yr and 4.9 +/- 1.5 cm/yr during the pre- and posttreatment periods, respectively. In achondroplasia, there was a significant increase in growth rate of only the lower segment (from 1.1 +/- 1.6 cm/yr to 3 +/- 1.2 cm/yr, P < 0.02). There was no significant acceleration in the growth of the upper segment and of the scanogram measurements of the long bones. No untoward effects were noted. Recombinant hGH increases short-term growth velocity in children with achondroplasia/hypochondroplasia. Unexpectedly, this treatment does not seem to have a lesser effect on limbs than on trunk growth rate and, therefore, during 1 yr of treatment, does not increase body disproportion.

Achondroplasia↗
PubMed1996

Atelosteogenesis type II is caused by mutations in the diastrophic dysplasia sulfate-transporter gene (DTDST): evidence for a phenotypic series involving three chondrodysplasias.

Atelosteogenesis type II (AO II) is a neonatally lethal chondrodysplasia whose clinical and histological characteristics resemble those of another chondrodysplasia, the much less severe diastrophic dysplasia (DTD). The similarity suggests a shared pathogenesis involving lesions in the same biochemical pathway and perhaps the same gene. DTD is caused by mutations in the recently identified diastrophic dysplasia sulfate-transporter gene (DTDST). Here, we report that AOII patients also have DTDST mutations, which lead to defective uptake of inorganic sulfate and insufficient sulfation of macromolecules by patient mesenchymal cells in vitro. Together with our recent observation that a third even more severe chondrodysplasia, achondrogenesis type IB, is also caused by mutations in DTDST, these results demonstrate a phenotypic series of three chondrodysplasias of increasing severity caused by lesions in a single sulfate-transporter gene. The severity of the phenotype appears to be correlated with the predicted effect of the mutations on the residual activity of the DTDST protein.

Anion Transport Proteins↗
PubMed1995

Medical genetics.

A landmark in cancer genetics in 1994 was the isolation of a gene for breast and ovarian cancer susceptibility (BRCA1). The Human Genome Project has had a profound effect on our ability to perform early prenatal diagnosis of genetic disease.

Genetic Testing↗
PubMed1995

Genetic homogeneity of cartilage-hair hypoplasia.

Cartilage-hair hypoplasia (CHH) is an autosomal recessive metaphyseal chondrodysplasia characterized by short stature and hypoplasia of the hair. Associated pleiotropic features include deficient erythrogenesis, impaired T-cell mediated immunity, Hirschsprung's disease, and an increased risk of malignancies. CHH is most prevalent among the Old Order Amish in the United States and among the Finns, but sporadic families have been described among many other populations. We have previously mapped the gene for CHH to the short arm of chromosome 9 in Finnish and Amish families. The CHH locus resides close to D9S163 within an interval of 1.5 cM flanked by D9S165 and D9S50. In order to investigate the genetic homogeneity of CHH in various populations, we studied nine families with no genealogical connections to either Amish or Finns. No recombinants were detected between the CHH gene and any of the three closest marker loci studied, suggesting that CHH in these families results from mutation(s) at the same locus as in the Amish and Finnish families.

Canada↗
PubMed1995

Thanatophoric dysplasia (types I and II) caused by distinct mutations in fibroblast growth factor receptor 3.

Thanatophoric dysplasia (TD), the most common neonatal lethal skeletal dysplasia, affects one out of 20,000 live births. Affected individuals display features similar to those seen in homozygous achondroplasia. Mutations causing achondroplasia are in FGFR3, suggesting that mutations in this gene may cause TD. A sporadic mutation causing a Lys650Glu change in the tyrosine kinase domain of FGFR3 was found in 16 of 16 individuals with one type of TD. Of 39 individuals with a second type of TD, 22 had a mutation causing an Arg248Cys change and one had a Ser371Cys substitution, both in the extracellular region of the protein. None of these mutations were found in 50 controls showing that mutations affecting different functional domains of FGFR3 cause different forms of this lethal disorder.

Alleles↗