The sound of silence: autosomal recessive congenital ichthyosis caused by a synonymous mutation in ABCA12

作者：Goldsmith Tomer; Fuchs Telem Dana; Israeli Shirli; Sarig Ofer; Padalon Brauch Gilly; Bergman Reuven; Indelman Margarita; Sprecher Eli^*; Nou**eck Janna

来源：Experimental Dermatology, 2013, 22(4): 251-254.

DOI：10.1111/exd.12110

• ABCA12
• ichthyosis
• mutation
• silent
• splicing

Autosomal recessive congenital ichthyosis refers to a heterogeneous group of cornification disorders of major impact on patients%26apos; life. The disease has been linked so far to mutations in 8 distinct genes. We report a consanguineous family of Arab Muslim origin with several members displaying a severe form of congenital ichthyosiform erythroderma. Using a panel of polymorphic microsatellite markers, we identified a region of homozygosity shared by all patients on 2q34, in a region harbouring the ABCA12 gene. Direct sequencing of genomic DNA derived from a patient failed to reveal any obviously pathogenic change in the coding sequence of this gene. In contrast, cDNA sequence analysis revealed the existence of a 163-bp-long deletion in exon 24, thus pointing to a splicing defect. Careful reanalysis of the genomic DNA sequence revealed apart from several known single-nucleotide polymorphisms, a hitherto unreported homozygous synonymous mutation in exon 24 (c.3456G%26gt;A; p.S1152S), which was found to lead to the formation of a novel splicing acceptor site. Synonymous mutations have been shown to uncommonly cause inherited disorders in humans. Here, we present the first example of a congenital form of ichthyosis resulting from such a genetic defect.

• 出版日期2013-4