Hum Mutat 2017 Apr 01;384:373-377. doi: 10.1002/humu.23171.

Heterozygous Pathogenic Variant in DACT1 Causes an Autosomal-Dominant Syndrome with Features Overlapping Townes-Brocks Syndrome.

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A heterozygous nonsense variant was identified in dapper, antagonist of beta-catenin, 1 (DACT1) via whole-exome sequencing in family members with imperforate anus, structural renal abnormalities, genitourinary anomalies, and/or ear anomalies. The DACT1 c.1256G>A;p.Trp419* variant segregated appropriately in the family consistent with an autosomal dominant mode of inheritance. DACT1 is a member of the Wnt-signaling pathway, and mice homozygous for null alleles display multiple congenital anomalies including absent anus with blind-ending colon and genitourinary malformations. To investigate the DACT1 c.1256G>A variant, HEK293 cells were transfected with mutant DACT1 cDNA plasmid, and immunoblotting revealed stability of the DACT1 p.Trp419* protein. Overexpression of DACT1 c.1256G>A mRNA in Xenopus embryos revealed a specific gastrointestinal phenotype of enlargement of the proctodeum. Together, these findings suggest that the DACT1 c.1256G>A nonsense variant is causative of a specific genetic syndrome with features overlapping Townes-Brocks syndrome.

???displayArticle.pubmedLink??? 28054444
???displayArticle.pmcLink??? PMC5390682
???displayArticle.link??? Hum Mutat
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Species referenced: Xenopus
Genes referenced: dact1
GO keywords: urogenital system development [+]

???displayArticle.disOnts??? Townes-Brocks syndrome
???displayArticle.omims??? TOWNES-BROCKS SYNDROME 1; TBS1
References [+] :