Curry C J, Magenis R E, Brown M, Lanman J T, Tsai J, O'Lague P, Goodfellow P, Mohandas T, Bergner E A, Shapiro L J
N Engl J Med. 1984 Oct 18;311(16):1010-5. doi: 10.1056/NEJM198410183111603.
We studied two families with an inherited deletion of the short arm of an X chromosome (Xp) in which affected male offspring have epiphyseal stippling in infancy (chondrodysplasia punctata), nasal hypoplasia, ichthyosis, and mental retardation. The presence of ichthyosis and the apparent pattern of X-linked recessive inheritance prompted investigation of the short arm of the X chromosome through studies of genetic markers and focused cytogenetic analysis. Biochemical studies suggested that there was a deletion of three genes previously mapped to the X-chromosome short arm, including the steroid sulfatase locus, the Xg locus, and the M1C2X locus. Prometaphase chromosomes demonstrated a deletion of Xp at p22.32 in the affected boys, in their obligate-carrier mothers, and in 11 of 25 women at risk as potential carriers. The women carrying the Xp deletion had normal gonadal function and fertility but were shorter than the noncarriers in their families (P less than 0.00001). These findings have implications for the genetic organization of this portion of the human X chromosome and demonstrate that small cytogenetic abnormalities may account for disorders with apparent mendelian patterns of inheritance.
我们研究了两个患有X染色体短臂（Xp）遗传性缺失的家族，其中受影响的男性后代在婴儿期有骨骺点状钙化（点状软骨发育不良）、鼻发育不全、鱼鳞病和智力发育迟缓。鱼鳞病的存在以及明显的X连锁隐性遗传模式促使我们通过基因标记研究和聚焦细胞遗传学分析对X染色体短臂进行调查。生化研究表明，三个先前定位于X染色体短臂的基因发生了缺失，包括类固醇硫酸酯酶基因座、Xg基因座和M1C2X基因座。前中期染色体显示，受影响男孩及其必然携带者母亲以及25名有潜在携带者风险的女性中有11名在p22.32处存在Xp缺失。携带Xp缺失的女性性腺功能和生育能力正常，但比其家族中的非携带者更矮（P小于0.00001）。这些发现对人类X染色体这一部分的基因组织具有启示意义，并表明小的细胞遗传学异常可能导致具有明显孟德尔遗传模式的疾病。
