Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9.
A human autosomal XY sex reversal locus, SRA1, associated with the skeletal malformation syndrome campomelic dysplasia (CMPD1), has been placed at distal 17q. The SOX9 gene, a positional candidate from the chromosomal location and expression pattern reported for mouse Sox9, was isolated and characterized. SOX9 encodes a putative transcription factor structurally related to the testis-determining factor SRY and is expressed in many adult tissues, and in fetal testis and skeletal tissue. Inactivating mutations on one SOX9 allele identified in nontranslocation CMPD1-SRA1 cases point to haploinsufficiency for SOX9 as the cause for both campomelic dysplasia and autosomal XY sex reversal. The 17q breakpoints in three CMPD1 translocation cases map 50 kb or more from SOX9.
Wagner
T
T
Institute of Human Genetics, University of Freiburg, Federal Republic of Germany.
Wirth
J
J
Meyer
J
J
Zabel
B
B
Held
M
M
Zimmer
J
J
Pasantes
J
J
Bricarelli
F D
FD
Keutel
J
J
Hustert
E
E
Wolf
U
U
Tommerup
N
N
Schempp
W
W
Scherer
G
G
D000595:Amino Acid Sequence; D001483:Base Sequence; D002356:Cartilage / Q000033:anatomy & histology; D002874:Chromosome Mapping; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D003001:Cloning, Molecular; D004268:DNA-Binding Proteins / Q000235:genetics; D012734:Disorders of Sex Development / Q000235:genetics*; D005260:Female; D005333:Fetus; D005360:Fibula / Q000033:anatomy & histology; D005819:Genetic Markers; D006609:High Mobility Group Proteins / Q000096:biosynthesis / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D009687:Nuclear Proteins; D010009:Osteochondrodysplasias / Q000235:genetics*; D010375:Pedigree; D012333:RNA, Messenger / Q000302:isolation & purification; D011994:Recombinant Proteins / Q000096:biosynthesis; D055758:SOX9 Transcription Factor; D017422:Sequence Analysis, DNA; D051876:Sex-Determining Region Y Protein; D013737:Testis / Q000033:anatomy & histology; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics*; D014158:Transcription, Genetic; D014178:Translocation, Genetic
D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006609:High Mobility Group Proteins; D009687:Nuclear Proteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D055758:SOX9 Transcription Factor; C527932:SOX9 protein, human; C497745:SRY protein, human; D051876:Sex-Determining Region Y Protein; C527933:Sox9 protein, mouse; D014157:Transcription Factors