Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form
Germline mosaicism in keratitis-ichthyosis-deafness syndrome: pre-natal diagnosis in a familial lethal form
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DOI：
10.1111/j.1399-0004.2009.01339.x
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发表时间：
2010-06-01
影响因子：
3.5
通讯作者：
Hadj-Rabia, S.
中科院分区：
文献类型：
--
作者：
Sbidian, E.;Feldmann, D.;Hadj-Rabia, S.
角膜炎-鱼鳞病-耳聋（KID）综合征是一种常染色体显性先天性外胚层缺陷，以皮肤病变、听力损失和角膜炎相关为特征。大多数病例似乎是零星的。KID综合征主要与编码连接蛋白26的GJB2基因突变有关。最近，在两名无关的白种人患者中报道了一种致命的疾病，发生在生命的第一年。这种罕见的致命形式是由GJB2基因的G45E突变引起的。我们在这里报告了与G45E突变有关的致命形式的KID综合征的第一个产前分子遗传学诊断。在同一家庭中，非洲非近亲健康父母所生的其他三个兄弟姐妹也出现这种情况，导致对最后一次怀孕进行产前诊断。分子分析证实了胎儿致命型KID的诊断。这些结果确定了种系嵌合体在KID综合征中的作用，值得仔细的遗传咨询。此外，对我们的病例和文献的分析使我们能够定义一个特征性的严重新生儿表型，包括面部畸形，严重角化伴大量局灶性皮肤角化过度伴红皮病，指甲营养不良，完全无毛和包皮缺失。
Keratitis-ichthyosis-deafness (KID) syndrome is an autosomal dominant congenital ectodermal defect characterized by the association of skin lesions, hearing loss and keratitis. Most of the cases appear to be sporadic. KID syndrome is mostly related to mutations of GJB2 gene encoding connexin-26. Recently, a lethal form of the disease during the first year of life has been reported in two unrelated Caucasian patients. This rare lethal form is caused by the G45E mutation of GJB2 gene. We here report the first pre-natal molecular genetic diagnosis of the lethal form of KID syndrome relating to a G45E mutation. In the same family, the occurrence of this condition in three other siblings born to African non-consanguineous healthy parents lead to perform pre-natal diagnosis for this last pregnancy. Molecular analysis confirms the diagnosis of the lethal form of KID for the fetus. These results establish the role of germline mosaicism in KID syndrome and warrant careful genetic counseling. Furthermore, analysis of our cases and the literature allowed us to define a characteristic severe neonatal phenotype including facial dysmorphy, severe cornification with massive focal hyperkeratosis of the skin with erythroderma, dystrophic nails, complete atrichia and absence of foreskin.