4.7 Article

Biallelic variant in DACH1, encoding Dachshund Homolog 1, defines a novel candidate locus for recessive postaxial polydactyly type A

Journal

GENOMICS
Volume 113, Issue 4, Pages 2495-2502

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.ygeno.2021.05.015

Keywords

Postaxial polydactyly (PAP); Cilia; Limb anomaly; Whole exome sequencing; DACH1 gene; Missense variant

Funding

  1. King Abdullah International Medical Research Centre (KAIMRC) [RC19/352/R]

Ask authors/readers for more resources

Polydactyly or hexadactyly often involves various gene variants, and this study reveals the significant role of the DACH1 gene in human digit development, which remains largely unexplored.
Polydactyly or hexadactyly is characterized by an extra digit/toe with or without a bone. Currently, variants in ten genes have been implicated in the non-syndromic form of polydactyly. DNA from a single affected individual having bilateral postaxial polydactyly was subjected to whole exome sequencing (WES), followed by Sanger sequencing. Homology modeling was performed for the identified variant and advance microscopy imaging approaches were used to reveal the localization of the DACH1 protein at the base of primary cilia. A disease-causing biallelic missense variant (c.563G > A; p.Cys188Tyr; NM_080760.5) was identified in the DACH1 gene segregating perfectly within the family. Structural analysis using homology modeling of the DACH1 protein revealed secondary structure change that might result in loss of function or influence downstream interactions. Moreover, siRNA-mediated depletion of DACH1 showed a key role of DACH1 in ciliogenesis and cilia function. This study provides the first evidence of involvement of the DACH1 gene in digits development in humans and its role in primary cilia. This signifies the importance and yet unexplored role of DACH1.

Authors

I am an author on this paper
Click your name to claim this paper and add it to your profile.

Reviews

Primary Rating

4.7
Not enough ratings

Secondary Ratings

Novelty
-
Significance
-
Scientific rigor
-
Rate this paper

Recommended

No Data Available
No Data Available