PDF(Pubmed)
Abstract：
HELIX syndrome (Hypohidrosis-Electrolyte disturbances-hypoLacrimia-Ichthyosis-Xerostomia) (MIM#617671) (ORPHA:528105), described in 2017, is due to an abnormal claudin 10 b protein, secondary to pathogenic CLDN10 variants. So far, only ten families have been described. We aim to describe the phenotype in the first Spanish family identified, highlight the skin anomalies as an important clue, and expand the genotypic spectrum. Two adult brothers from consanguineous parents with suspected ectodermal dysplasia (ED) since early childhood were re-evaluated. A comprehensive phenotypic exam and an aCGH + SNP4 × 180 K microarray followed by Sanger sequencing of the CLDN10 gene were performed. They presented hypohidrosis, xerosis, mild ichthyosis, plantar keratosis, palm hyperlinearity, alacrima, and xerostomia. In adulthood, they also developed a salt-losing nephropathy with hypokalemia and hypermagnesemia. The molecular study in both patients revealed a novel pathogenic homozygous deletion of 8 nucleotides in exon 2 of the CLDN10 gene [CLDN10 (NM_0006984.4): c.322_329delGGCTCCGA, p.Gly108fs*] leading to a premature truncation of the protein. Both parents were heterozygous carriers. Hypohidrosis, ichthyosis, and plantar keratosis associated with alacrima and xerostomia should raise suspicion for HELIX syndrome, which also includes nephropathy and electrolyte disturbances in adults. Given the potential for ED misdiagnosis in infancy, it is important to include the CLDN10 gene in a specific genodermatosis next-generation sequencing (NGS) panel to provide early diagnosis, accurate management, and genetic counseling.
摘要：
HELIX综合征（少汗症-电解质紊乱-低氧血症-鱼鳞病-口干症）（MIM＃617671）（ORPHA：528105），在2017年描述，是由于claudin10b蛋白异常，继发于致病性CLDN10变体。到目前为止,只描述了十个家庭。我们的目的是描述第一个西班牙家族的表型，突出皮肤异常作为重要线索，并扩大基因型谱。重新评估了两名来自近亲父母的成年兄弟，他们自童年以来就怀疑患有外胚层发育不良（ED）。进行了全面的表型检查和aCGHSNP4×180K微阵列，然后对CLDN10基因进行Sanger测序。他们表现为多汗症，干燥症,轻度鱼鳞病,足底角化病,手掌超线性,假象,还有口干症.成年后,他们还发展了一种伴有低钾血症和高镁血症的失盐肾病。两名患者的分子研究揭示了CLDN10基因外显子2中8个核苷酸的新致病性纯合缺失[CLDN10（NM_0006984.4）：c.322_329delGGCTCCGA，p.Gly108fs*]导致蛋白质过早截短。父母双方都是杂合携带者。多汗症,鱼鳞病,足底角化病与唇裂和口干症相关应引起对HELIX综合征的怀疑，其中还包括成人肾病和电解质紊乱。考虑到婴儿期ED误诊的可能性，重要的是将CLDN10基因包括在特定的遗传性皮肤病下一代测序（NGS）面板中，以提供早期诊断，精准管理,和遗传咨询。
