Mutations in SOX9, the gene responsible for campomelic dysplasia and autosomal sex reversal
- St. George`s Hospital Medical School, London (United Kingdom); and others
Campomelic dysplasia (CD) is a skeletal malformation syndrome frequently accompanied by 46,XY sex reversal. A mutation-screening strategy using SSCP was employed to identify mutations in SOX9, the chromosome 17q24 gene responsible for CD and autosomal sex reversal in man. We have screened seven CD patients with no cytologically detectable chromosomal aberrations and two CD patients with chromosome 17 rearrangements for mutations in the entire open reading frame of SOX9. Five different mutations have been identified in six CD patients: two missense mutations in the SOX9 putative DNA binding domain (high mobility group, or HMG, box); three frameshift mutations and a splice-acceptor mutation. An identical frameshift mutation is found in two unrelated 46,XY patients, one exhibiting a male phenotype and the other displaying a female phenotype (XY sex reversal). All mutations found affect a single allele, which is consistent with a dominant mode of inheritance. No mutations were found in the SOX9 open reading frame of two patients with chromosome 17q rearrangements, suggesting that the translocations affect SOX9 expression. These findings are consistent with the hypothesis that CD results from haploinsufficiency of SOX9. 27 refs., 3 figs., 3 tabs.
- OSTI ID:
- 209893
- Journal Information:
- American Journal of Human Genetics, Vol. 57, Issue 5; Other Information: PBD: Nov 1995
- Country of Publication:
- United States
- Language:
- English
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Related Subjects
BASIC STUDIES
HUMAN CHROMOSOME 17
GENETIC MAPPING
CHROMOSOMAL ABERRATIONS
PATIENTS
HEREDITARY DISEASES
PHENOTYPE
SKELETAL DISEASES
CONGENITAL MALFORMATIONS
UROGENITAL SYSTEM DISEASES
GENES
MUTATION FREQUENCY
GENE MUTATIONS
SPLICING
STRUCTURE-ACTIVITY RELATIONSHIPS
SCREENING
DOMINANT MUTATIONS