Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.
Mutations in ABCA12 underlie the severe congenital skin disease harlequin ichthyosis.
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DOI：
10.1086/429844
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发表时间：
2005-05
影响因子：
9.8
通讯作者：
D. Kelsell;E. Norgett;Harriet C Unsworth;M. Teh;T. Cullup;C. Mein;P. Dopping-Hepenstal;B. Dale;G. Tadini;P. Fleckman;K. Stephens;V. Sybert;S. Mallory;B. North;D. Witt;E. Sprecher;A. Taylor;A. Ilchyshyn;C. Kennedy;H. Goodyear;C. Moss;D. Paige;J. Harper;B. Young;I. Leigh;R. Eady;E. O’Toole
中科院分区：
文献类型：
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作者：
D. Kelsell;E. Norgett;Harriet C Unsworth;M. Teh;T. Cullup;C. Mein;P. Dopping-Hepenstal;B. Dale;G. Tadini;P. Fleckman;K. Stephens;V. Sybert;S. Mallory;B. North;D. Witt;E. Sprecher;A. Taylor;A. Ilchyshyn;C. Kennedy;H. Goodyear;C. Moss;D. Paige;J. Harper;B. Young;I. Leigh;R. Eady;E. O’Toole
花斑鱼鳞病（HI）是最严重的和经常致命的形式隐性先天性鱼鳞病。虽然脂质转运，蛋白磷酸酶活性和分化的缺陷已被描述，HI的临床和细胞表型的遗传基础尚未确定。通过使用单核苷酸多态性芯片技术和纯合性定位，在5例HI患者的染色体区域2q35中观察到一个共同的纯合性区域。ABCA12基因的测序，其中地图内的纯合性定位定义的最小区域，揭示了疾病相关的突变，包括大的基因内缺失和移码缺失的11个筛选的12个HI的个人。由于HI表皮显示异常的层状颗粒形成，ABCA 12可能在层状颗粒的形成和脂质向细胞间隙的排放中起关键作用，这将解释在这种疾病中观察到的表皮屏障缺陷。这一发现为早期产前诊断铺平了道路。此外，ABCA 12的功能研究将导致更好地理解表皮分化和屏障形成。
Harlequin ichthyosis (HI) is the most severe and frequently lethal form of recessive congenital ichthyosis. Although defects in lipid transport, protein phosphatase activity, and differentiation have been described, the genetic basis underlying the clinical and cellular phenotypes of HI has yet to be determined. By use of single-nucleotide-polymorphism chip technology and homozygosity mapping, a common region of homozygosity was observed in five patients with HI in the chromosomal region 2q35. Sequencing of the ABCA12 gene, which maps within the minimal region defined by homozygosity mapping, revealed disease-associated mutations, including large intragenic deletions and frameshift deletions in 11 of the 12 screened individuals with HI. Since HI epidermis displays abnormal lamellar granule formation, ABCA12 may play a critical role in the formation of lamellar granules and the discharge of lipids into the intercellular spaces, which would explain the epidermal barrier defect seen in this disorder. This finding paves the way for early prenatal diagnosis. In addition, functional studies of ABCA12 will lead to a better understanding of epidermal differentiation and barrier formation.