Endocrinology Service, Hospital de Pediatria Garrahan, Buenos Aires, Argentina.
Horm Res Paediatr. 2011;75(1):70-7. doi: 10.1159/000320029. Epub 2010 Sep 22.
Three novel heterozygous SF-1 gene mutations affecting multiple members of two unrelated families with a history of 46,XY disorders of sex development (DSD) and 46,XX ovarian insufficiency are described.
clinical and mutational analysis of the SF-1 gene in 9 subjects of two families.
family 1 had 2 affected 46,XY DSD subjects. One, born with severe perineal hypospadias, was raised as a male, and presented normal adolescence. The other, born with ambiguous genitalia, uterus, and mild testicular dysgenesis, was raised as a female. A W279X heterozygous mutation and an intronic deletion (g3314-3317delTCTC (IVS 4 + 8) was found in the SF-1 gene. In family 2, 4/6 affected siblings had 46,XY DSD or hypospadias. An affected 46,XX sister had normal sexual development but increased FSH levels. The 37-year-old affected mother had entered menopause. An Y183X heterozygous mutation was detected.
an extreme within-family phenotypic variability, ranging from severe prenatal undervirilization to normal pubertal development, was observed in 46,XY-affected siblings, indicating that other unknown factors might be involved in the phenotype. Low ovarian reserve and preserved fertility in 46,XX subjects can be observed in heterozygous SF-1 gene mutations.
三个新的 SF-1 基因突变影响了两个无关家族的多个成员，这些家族都有 46,XY 性发育障碍 (DSD) 和 46,XX 卵巢功能不全的病史。
对两个家族的 9 名受试者的 SF-1 基因进行临床和突变分析。
家族 1 有 2 名受影响的 46,XY DSD 受试者。一名出生时患有严重的会阴型尿道下裂，被抚养为男性，青春期正常。另一名出生时外生殖器、子宫和轻度睾丸发育不良，被抚养为女性。在 SF-1 基因中发现了一个 W279X 杂合突变和一个内含子缺失 (g3314-3317delTCTC (IVS 4 + 8)。在家族 2 中，4/6 名受影响的兄弟姐妹有 46,XY DSD 或尿道下裂。一名受影响的 46,XX 姐妹性发育正常，但 FSH 水平升高。37 岁的受影响母亲已进入更年期。检测到一个 Y183X 杂合突变。
在 46,XY 受影响的兄弟姐妹中观察到了一种极端的家族内表型变异性，从严重的产前雄激素不足到正常的青春期发育，表明可能涉及其他未知因素。在 SF-1 基因突变的杂合子中可以观察到 46,XX 受试者的低卵巢储备和保留生育能力。
