Zanaria E, Bardoni B, Dabovic B, Calvari V, Fraccaro M, Zuffardi O, Camerino G
Università di Pavia, Italy.
Philos Trans R Soc Lond B Biol Sci. 1995 Nov 29;350(1333):291-6. doi: 10.1098/rstb.1995.0164.
Male to female sex reversal has been observed in individuals with duplications of the short arm of the X chromosome. The study of Xp duplicated patients demonstrated that sex reversal results from the presence of two active copies of the DSS (dosage sensitive sex reversal) locus. A double dosage of DSS disrupts testis formation whereas its absence is compatible with a male phenotype, suggesting a role for DSS in ovarian development and as a link between ovary and testis formation. DSS was localized to a 160 kb region of Xp21, overlapping the adrenal hypoplasia congenita locus. The search for expressed sequences in the DSS critical region led to the identification of two types of genes: the DAM family and DAX-1, an atypical member of the nuclear receptor superfamily. Although no function is currently known for DAM genes, functional deficiency for DAX-1 has been shown to be responsible for adrenal hypoplasia congenita and hypogonadotropic hypogonadism. The search for the DSS gene(s) is still open and both the DAM genes and DAX-1 represent DSS candidate genes.
在X染色体短臂重复的个体中观察到了男性向女性的性反转。对Xp重复患者的研究表明，性反转是由于存在两个活性拷贝的DSS（剂量敏感性性反转）位点所致。DSS的双倍剂量会破坏睾丸形成，而其缺失则与男性表型相符，这表明DSS在卵巢发育中起作用，并作为卵巢和睾丸形成之间的联系。DSS定位于Xp21的一个160 kb区域，与先天性肾上腺发育不全位点重叠。在DSS关键区域寻找表达序列导致鉴定出两种类型的基因：DAM家族和DAX-1，后者是核受体超家族的一个非典型成员。尽管目前尚不清楚DAM基因的功能，但已证明DAX-1的功能缺陷是先天性肾上腺发育不全和低促性腺激素性性腺功能减退的原因。对DSS基因的搜索仍在进行中，DAM基因和DAX-1都是DSS候选基因。
