Calvari V, Bertini V, De Grandi A, Peverali G, Zuffardi O, Ferguson-Smith M, Knudtzon J, Camerino G, Borsani G, Guioli S
Dipartimento Patologia Umana ed Ereditaria, Università degli Studi di Pavia, Italy.
Genomics. 2000 May 1;65(3):203-12. doi: 10.1006/geno.2000.6160.
Male to female sex reversal has been described in patients with deletions of chromosome 9p, and a region critical for sex reversal has been localized to p24.3, at the tip of the chromosome (TD9). It was proposed that the sex reversal may arise by haploinsufficiency for a gene localized to the minimum deletion. The 9p24.3 genes DMRT1 and DMRT2 are the favorite TD9 candidates to date, in virtue of their sequence similarity to doublesex and mab-3, sexual regulators in Drosophila and Caenorhabditis elegans, respectively. The hypothesis of sex reversal by combined haploinsufficiency for the two genes was put forward to explain the lack of mutations in either gene in XY sex-reversed females. Here we describe a XY sex-reversed patient carrying a novel 9p deletion that extends over less than 700 kb of genomic DNA. This region defines the smallest interval for sex reversal found to date. DMRT1 and DMRT2 map outside this region. Our data do not support the hypothesis of combined haploinsufficiency for DMRT1 and DMRT2. Nevertheless, DMRT1 localizes very close to the deletion breakpoint and has a pattern of expression compatible with a role in sex determination. It therefore remains a candidate gene for 9p sex reversal.
在9号染色体短臂缺失的患者中已发现男性向女性性反转的现象，并且一个对性反转至关重要的区域已定位到染色体末端的p24.3（TD9）。有人提出，性反转可能是由于定位于最小缺失区域的一个基因单倍剂量不足所致。9p24.3基因DMRT1和DMRT2是目前最有可能的TD9候选基因，因为它们的序列分别与果蝇和秀丽隐杆线虫中的性别调节因子doublesex和mab - 3相似。有人提出，由于XY性反转女性中这两个基因均未发现突变，因此可能是这两个基因联合单倍剂量不足导致性反转。在此，我们描述了一名XY性反转患者，其携带一个新的9号染色体短臂缺失，缺失区域小于700 kb的基因组DNA。该区域确定了迄今为止发现的最小性反转区间。DMRT1和DMRT2定位于该区域之外。我们的数据不支持DMRT1和DMRT2联合单倍剂量不足的假说。然而，DMRT1定位非常接近缺失断点，并且其表达模式与性别决定中的作用相符。因此，它仍然是9号染色体短臂性反转的候选基因。
