Deletion mutations of the Bs-alpha gene in patients with Albright hereditary osteodystrophy: Possible mutation hot-spot in exon 7
- NIDK, NIH, Bethesda, MD (United States)
- Indiana Univ., Indianapolis (United States)
- Univ. of Wuerzberg (Germany); and others
Albright hereditary osteodystrophy (AHO) is an autosomal dominant disease characterized by short stature, centripetal obesity, subcutaneous ossifications and focal brachydactyly. Patients with this disorder may have these features alone (pseudopseudohypoparathyroidism) or these features in association with resistance to multiple hormones which raise intracellular cAMP (pseudohypoparathyroidism, PHP). In most kindreds, affected members have decreased function of the G protein Gs and decreased levels of the Gs{alpha}-subunit. Heterozygous inactivating mutations of the Gs{alpha} gene have been previously identified in AHO. Exons 2-13 of the Gs{alpha} gene and their splice junctions were PCR-amplified and the products analyzed by temperature gradient gel electrophoresis (TGGE) and direct sequencing. Using this approach, a new heterozygous 2 bp deletion in exon 4 creating a premature stop codon was identified in 5 affected members of a previously reported family. The mutation was not present in an unaffected family member. We also have identified a previously reported 4 bp deletion in the coding region of exon 7 in 2 further unrelated sporadic cases of PHP. In one case, the mutation was absent in her siblings and in both parents, confirming that this is a de novo mutation in this patient. This specific 4 bp deletion has now been reported in 4 PHP patients, at least 3 of whom are unrelated. These results suggest that this region of the Gs{alpha} gene may be a hot-spot for deletions.
- OSTI ID:
- 134777
- Report Number(s):
- CONF-941009-; ISSN 0002-9297; TRN: 95:005313-1516
- Journal Information:
- American Journal of Human Genetics, Vol. 55, Issue Suppl.3; Conference: 44. annual meeting of the American Society of Human Genetics, Montreal (Canada), 18-22 Oct 1994; Other Information: PBD: Sep 1994
- Country of Publication:
- United States
- Language:
- English
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