常染色体性反转和弯肢侏儒症是由与SRY相关的基因SOX9及其周围的突变引起的。

Autosomal sex reversal and campomelic dysplasia are caused by mutations in and around the SRY-related gene SOX9.

作者信息

Wagner T, Wirth J, Meyer J, Zabel B, Held M, Zimmer J, Pasantes J, Bricarelli F D, Keutel J, Hustert E, Wolf U, Tommerup N, Schempp W, Scherer G

机构信息

Institute of Human Genetics, University of Freiburg, Federal Republic of Germany.

出版信息

Cell. 1994 Dec 16;79(6):1111-20. doi: 10.1016/0092-8674(94)90041-8.

DOI:10.1016/0092-8674(94)90041-8

PMID:8001137

Abstract

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.

摘要

一个与骨骼发育不良综合征（CMPD1）相关的人类常染色体XY性反转位点SRA1已被定位到17号染色体长臂远端。根据小鼠Sox9报道的染色体位置和表达模式，分离并鉴定了作为位置候选基因的SOX9基因。SOX9编码一种假定的转录因子，其结构与睾丸决定因子SRY相关，在许多成年组织以及胎儿睾丸和骨骼组织中表达。在非易位CMPD1 - SRA1病例中鉴定出的一个SOX9等位基因的失活突变表明，SOX9单倍剂量不足是导致骨骼发育不良和常染色体XY性反转的原因。三例CMPD1易位病例中的17号染色体长臂断点位于距SOX9基因50 kb或更远的位置。