Identification of novel mutations in the ABCA12 gene, c.1857delA and c.5653-5655delTAT, causing harlequin ichthyosis

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• 作者：Johannes Follmann ; Doris Macchiella ; Catharina Whybra ; Eva Mildenberger ; Cornelia Poarangan ; Ulrich Zechner ; Oliver Bartsch
• 关键词：ABCA12 ; ATP-binding cassette ; subfamily A ; member 12 ; bp ; base pair ; HI ; harlequin ichthyosis ; NCBI ; National Center for Biotechnology Information ; no ; number ; OMIM ; Online Mendelian Inheritance in Man ; 3D ; three-dimensional ; UniProt ; Universal Protein Re
• 刊名：Gene
• 出版年：2013
• 出版时间：1 December, 2013
• 年：2013
• 卷：531
• 期：2
• 页码：510-513
• 全文大小：414 K

文摘

Harlequin ichthyosis (HI) is a severe autosomal recessive developmental disorder of the skin that is frequently but not always fatal in the first few days of life. In HI, mutations in both ABCA12 gene alleles must have a severe impact on protein function and most mutations are truncating. The presence of at least one nontruncating mutation (predicting a residual protein function) usually causes a less severe congenital ichthyosis (lamellar ichthyosis or congenital ichthyosiform erythroderma). Here we report on a girl with severe HI diagnosed by prenatal ultrasound at 33 5/7 week gestation. Ultrasound findings included ectropion, eclabium, deformed nose, hands and feet, joint contractures, hyperechogenic amniotic fluid and polyhydramnion. After birth, palliative treatment was provided and she died on her first day of life. Sequence analysis of the ABCA12 gene identified two novel mutations, c.1857delA (predicting p.Lys619*) in exon 15 and c.5653-5655delTAT (predicting p.1885delTyr) in exon 37, each in heterozygous state. The c.5653-5655delTAT mutation is not truncating, but the deleted tyrosine at position 1885 is perfectly conserved among vertebrates and molecular studies evaluated the mutation as probably disease causing and damaging.