A novel germ line mutation in SOX9 causes familial campomelic dysplasia and sex reversal.

Familial 46,XY sex reversal without campomelic dysplasia caused by a deletion upstream of the SOX9 gene.

BACKGROUND 46,XY sex reversal is a rare disorder and familial cases are even more rare. The purpose of the present study was to determine the molecular basis for a family with three affected siblings who had 46,XY sex reversal. METHODS DNA was extracted from three females with 46,XY sex reversal, two normal sisters, and both unaffected parents. All protein coding exons of the SRY and NR5A1 ge...

Mutational analysis of the SOX9 gene in campomelic dysplasia and autosomal sex reversal: lack of genotype/phenotype correlations.

It has previously been shown that, in the heterozygous state, mutations in the SOX9 gene cause campomelic dysplasia (CD) and the often associated autosomal XY sex reversal. In 12 CD patients, 10 novel mutations and one recurrent mutation were characterized in one SOX9 allele each, and in one case, no mutation was found. Four missense mutations are all located within the high mobility group (HMG...

Evidence to exclude SOX9 as a candidate gene for XY sex reversal without skeletal malformation.

The skeletal malformation syndrome campomelic dysplasia (CMD1) is caused by mutations within the SOX9 gene or chromosomal rearrangement breakpoints outside SOX9. Approximately three quarters of cases of CMD1 in XY subjects show complete or partial sex reversal. As some mutations cause CMD1 alone and others cause CMD1 and sex reversal, it is conceivable that some mutations might cause sex revers...

Screening of the 1 Mb SOX9 5' control region by array CGH identifies a large deletion in a case of campomelic dysplasia with XY sex reversal.

Novel SOX9 expression during human pancreas development correlates to abnormalities in Campomelic dysplasia

Haploinsufficiency of SOX9, which encodes a homeodomain transcription factor, results in Campomelic dysplasia. Classical features of this disorder (e.g. skeletal dysplasia and 46,XY sex reversal) are in concordance with SOX9 expression profiles during human embryonic development. We report the robust expression of SOX9 throughout the pancreas during human embryogenesis, at levels of detection e...