PubMed Health⌕ Search

Biomedical subjects

J T Hecht

Publications and source records attributed to J T Hecht.

At least 73 records · Page 4Linked to original sources
PubMed1994

Evidence, from family studies, for linkage disequilibrium between TGFA and a gene for nonsyndromic cleft lip with or without cleft palate.

The inheritance of alleles of the transforming growth factor alpha (TGFA) locus has been studied in families affected with cleft lip with or without cleft palate (CL/P), by using the transmission/disequilibrium test described by Spielman and colleagues. Only heterozygous parents with an affected child can be included in this test, but within such families a significantly greater frequency of C2 alleles were transmitted to affected children than would be expected by chance. There was no evidence that the total number of C2 alleles transmitted to affected and unaffected children differed significantly from random segregation. These data provide evidence from within families that a gene for susceptibility to CL/P is in significant linkage disequilibrium with the C2 allele of the TGFA locus.

Alleles↗
PubMed1993

Familial interstitial deletion 11(p11.12p12) associated with parietal foramina, brachymicrocephaly, and mental retardation.

Parietal foramina may be an isolated autosomal dominant trait or found in syndromes. We report on two related individuals who have multiple anomalies with parietal foramina and the deletion of 11(p11.12p12) due to the inheritance of a derivative chromosome 11 from an insertional translocation dir ins (13;11)(q14.1; p11.12p12). Results of initial chromosome analyses on the proposita and her maternal half-uncle were reported as normal. However, the clinical manifestations and family history suggested a chromosomal cause and cytogenetic studies were performed on the proposita's mother. A derivative chromosome 13 was initially identified and further evaluation documented a derivative 11 as the reciprocal product. This family illustrates the importance of performing chromosome studies on the normal intervening relatives in families with multiple affected individuals with mental retardation and minor anomalies as one of the two reciprocal products may be more easily detectable in a balanced carrier. Additionally, the finding of del(11)(p11.12p12) may provide a map location for a syndrome which includes parietal foramina.

Abnormalities, Multiple↗
PubMed1993

Linkage of typical pseudoachondroplasia to chromosome 19.

Pseudoachondroplasia (PSACH) is an autosomal dominant dwarfing condition associated with disproportionate short stature, marked joint deformities, and early onset osteoarthritis. Previous linkage studies have excluded linkage to cartilage and noncartilagenous extracellular matrix candidate genes. Here, we report mapping the pseudoachondroplasia gene to chromosome 19. Maximum lod scores of 4.70, 4.15, and 4.86 at theta = 0.00 were found for D19S212, D19S215, and D19S49, respectively. Multipoint analysis suggests the following order: D19S253-D19S199-(D19S212/PSACH/D19S215)-++ +D19S222-D19S49.

Achondroplasia↗
PubMed1993

A type X collagen mutation causes Schmid metaphyseal chondrodysplasia.

The expression of type X collagen is restricted to hypertrophic chondrocytes in regions undergoing endochondral ossification, such as growth plates. The precise function of type X collagen is unknown but the tissue-specific expression prompted us to examine the gene in hereditary disorders of cartilage and bone growth (osteochondrodysplasias). We have identified a 13 base pair deletion in one type X collagen allele segregating with autosomal dominant Schmid metaphyseal chondrodysplasia in a large Mormon kindred (lod score = 18.2 at theta = 0). The mutation produces a frameshift which alters the highly conserved C-terminal domain of the alpha 1(X) chain and reduces the length of the polypeptide by nine residues. This mutation may prevent association of the mutant polypeptide during trimer formation, resulting in a decreased amount of normal protein.

Alleles↗
PubMed1993

Nonsyndromic cleft lip and palate: no evidence of linkage to HLA or factor 13A.

Nonsyndromic cleft lip with or without cleft palate (CLP) is a common craniofacial anomaly, the etiology of which is not known. Population studies have shown that a large proportion of cases occur sporadically. Recently, segregation analyses applied to CLP families have demonstrated that an autosomal dominant/codominant gene(s) may cause clefting in cases. Associations of autosomal dominant CLP and nonsyndromic cleft palate (CP) with HLA and F13A genes on chromosome 6p have been suggested previously. Linkage to these two areas on chromosome 6p were tested in 12 autosomal dominant families with CLP. With a LOD score of -2 or less for exclusion, no evidence of linkage was found to four chromosome 6p markers. Multipoint analysis showed no evidence of a clefting locus in this region spanning 54 cM on chromosome 6p in these CLP families.

Chromosomes, Human, Pair 6↗
PubMed1992

Exclusion of human proteoglycan link protein (CRTL1) and type II collagen (COL2A1) genes in pseudoachondroplasia.

Patients with pseudoachondroplasia have a skeletal dysplasia with marked short stature. The most common cause of this condition is an autosomal dominant mutation, although autosomal recessive inheritance has been reported. Linkage to 2 cartilage-specific candidate genes, type II collagen (COL2A1) and proteoglycan link protein genes (CRTL1), was tested in 9 autosomal dominant families with pseudoachondroplasia. Tight linkage to these candidate genes was excluded with LOD scores for COL2A1 of -2.45 at theta = 0.05 and for CRTL1 of -7.28 at theta = 0.001. Discordant inheritance of the disease phenotype with each of these genes was also observed. Thus, these 2 candidate genes can be excluded as the cause of disease in these families.

Collagen↗
PubMed1992

Growth hormone therapy in achondroplasia.

A pilot study was carried out to examine the safety and efficacy of recombinant human growth hormone for growth-promoting therapy of achondroplasia. The data suggest that the agent in doses used to treat non-GH-deficient forms of short stature (0.3 mg/kg/wk) modestly increases overall height velocity in some children with achondroplasia. The effect was seen mainly in children with the lowest growth velocities prior to treatment. No untoward effects were noted. Several questions were raised that require further study.

Achondroplasia↗
PubMed1992

SSCP and segregation analysis of the human type X collagen gene (COL10A1) in heritable forms of chondrodysplasia.

Type X collagen is a homotrimeric, short chain, nonfibrillar collagen that is expressed exclusively by hypertrophic chondrocytes at the sites of endochondral ossification. The distribution and pattern of expression of the type X collagen gene (COL10A1) suggests that mutations altering the structure and synthesis of the protein may be responsible for causing heritable forms of chondrodysplasia. We investigated whether mutations within the human COL10A1 gene were responsible for causing the disorders achondroplasia, hypochondroplasia, pseudoachondroplasia, and thanatophoric dysplasia, by analyzing the coding regions of the gene by using PCR and the single-stranded conformational polymorphism technique. By this approach, seven sequence changes were identified within and flanking the coding regions of the gene of the affected persons. We demonstrated that six of these sequence changes were not responsible for causing these forms of chondrodysplasia but were polymorphic in nature. The sequence changes were used to demonstrate discordant segregation between the COL10A1 locus and achondroplasia and pseudoachondroplasia, in nuclear families. This lack of segregation suggests that mutations within or near the COL10A1 locus are not responsible for these disorders. The seventh sequence change resulted in a valine-to-methionine substitution in the carboxyl-terminal domain of the molecule and was identified in only two hypochondroplasic individuals from a single family. Segregation analysis in this family was inconclusive, and the significance of this substitution remains uncertain.

Base Sequence↗
PubMed1992

Xeroderma pigmentosum and Cockayne syndrome: overlapping clinical and biochemical phenotypes.

Two siblings are described whose clinical presentation of cutaneous photosensitivity and central nervous system dysfunction is strongly reminiscent of the DeSanctis-Cacchione syndrome (DCS) variant of xeroderma pigmentosum. An extensive clinical evaluation supported a diagnosis of DCS and documented previously unreported findings. In vitro fibroblast studies showed UV sensitivity that was two to three times that of normal controls. However, neither a post-UV-irradiation DNA excision-repair defect indicative of XP nor a semiconservative DNA replication defect indicative of XP variant was found. Rather, a failure of RNA synthesis to recover to normal levels after UV exposure was observed, a biochemical abnormality seen in Cockayne syndrome (CS), one of the premature-aging syndromes with clinical UV sensitivity. These patients, therefore, clinically have XP, but their biochemical characteristics suggest CS. The reason(s) for the severe neurologic disease, in light of the relatively mild cutaneous abnormalities, is unclear. Other cases with unusual fibroblast responses to irradiation have been noted in the literature and, along with the data from our patients, reinforce the notion of the complexity of DNA maintenance and repair.

Child↗
PubMed1991

Cognitive and motor skills in achondroplastic infants: neurologic and respiratory correlates.

Thirteen infants with achondroplasia underwent psychometric testing as part of a comprehensive neurologic assessment. As a group, mental development was average and motor development was delayed, although a wide range of scores was obtained. Foramen magnum measurements were correlated with respiratory dysfunction, abnormal somatosensory evoked potentials, and delayed motor development. Abnormal polysomnogram outcome was associated with reduced mental capacity. In light of the reported increased frequency of respiratory dysfunction in achondroplasia, these findings warrant careful attention and further study.

Achondroplasia↗
PubMed1991

Molecular analysis of overlapping chromosomal deletions in patients with Langer-Giedion syndrome.

We have obtained lymphoblastoid cell lines from three patients with Langer-Giedion syndrome who have overlapping deletions in 8q24.1. To isolate the deletion chromosomes from their normal homologs, patient cell lines were fused with hamster cells and hybrid cells were selected for retention of human chromosome 8. These hybrid cell lines were screened for the presence of chromosome 8 by fluorescence in situ hybridization and by Southern blot hybridization. We have hybridized 31 recombinant DNA clones derived from the 8q22-qter region to Southern blots of the hybrid cell lines; 8 were found to lie within the deletion of at least one patient. One clone identified sequences that were missing from one copy of chromosome 8 in all three patients. These clones help to further define the deletions in these patients and will serve as starting points for detailed characterization of the region.

Animals↗
PubMed1991

Analysis of the chondroitin sulfate proteoglycan core protein (CSPGCP) gene in achondroplasia and pseudoachondroplasia.

Achondroplasia and pseudoachondroplasia are autosomal dominant skeletal dysplasias resulting in short-limbed dwarfism. Histologic and ultrastructural studies of the cartilage in pseudoachondroplasia and in homozygous achondroplasia have suggested a structural abnormality in chondroitin sulfate proteoglycan (CSPG), a major structural protein in the extra-cellular matrix. The gene encoding CSPG core protein (CSPGCP) is thus a logical "candidate gene" for analysis in these conditions. cDNA probes encoding CSPGCP were used to identify restriction fragment length polymorphisms (RFLPs) in DNA from a panel of control individuals. No gross alterations at the CSPGCP locus were noted in DNA from 37 individuals with achondroplasia and 5 individuals with pseudoachondroplasia. In addition, allelic frequencies of the RFLPs were not significantly different among controls and patients with either condition. In one three-generation family with achondroplasia, close linkage of the CSPGCP locus and the skeletal dysplasia was excluded using a Bgl II polymorphism. Similarly, in a three-generation family with pseudoachondroplasia, the CSPGCP gene was not tightly linked to the disease phenotype. These results indicate that mutations at the chondroitin sulfate proteoglycan core protein locus do not cause achondroplasia or pseudoachondroplasia in these families.

Achondroplasia↗