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Published on: August 20, 2019
WNT10A missense mutation associated with a complete odonto-onycho-dermal dysplasia syndrome
Sadia Nawaz1, Joakim Klar, Muhammad Wajid
1Human Molecular Genetics Laboratory, Health Biotechnology Division, National Institute for Biotechnology and Genetic Engineering, Faisalabad, Pakistan.
Abstract:
Wnt signalling is one of a few pathways that are crucial for controlling genetic programs during embryonic development as well as in adult tissues. WNT10A is expressed in the skin and epidermis and it has shown to be critical for the development of ectodermal appendages. A nonsense mutation in WNT10A was recently identified in odonto-onycho-dermal dysplasia (OODD; MIM 257980), a rare syndrome characterised by severe hypodontia, nail dystrophy, smooth tongue, dry skin, keratoderma and hyperhydrosis of palms and soles. We identified a large consanguineous Pakistani pedigree comprising six individuals affected by a complete OODD syndrome. Autozygosity mapping using SNP array analysis showed that the affected individuals are homozygous for the WNT10A gene region. Subsequent mutation screening showed a homozygous c.392C>T transition in exon 3 of WNT10A, which predicts a p.A131V substitution in a conserved alpha-helix domain. We report here on the first inherited missense mutation in WNT10A with associated ectodermal features.
Insights
A novel WNT10A gene mutation causes odonto-onycho-dermal dysplasia (OODD), a rare genetic disorder affecting ectodermal appendages. This study identifies the first inherited missense mutation in WNT10A linked to OODD syndrome.
Area of Science:
- Genetics
- Developmental Biology
- Dermatology
Background:
- Wnt signaling pathways are essential for embryonic development and adult tissue maintenance.
- WNT10A plays a critical role in the development of ectodermal appendages, including skin and hair.
- Odonto-onycho-dermal dysplasia (OODD) is a rare syndrome characterized by dental, nail, and skin abnormalities.
Purpose of the Study:
- To investigate the genetic basis of OODD in a Pakistani family.
- To identify mutations in the WNT10A gene associated with OODD syndrome.
Main Methods:
- Autozygosity mapping using SNP array analysis to identify homozygous regions in affected individuals.
- Mutation screening of the WNT10A gene in the identified Pakistani pedigree.
- Genetic analysis to pinpoint specific mutations and their predicted protein alterations.
Main Results:
- A large consanguineous Pakistani family with six individuals affected by OODD syndrome was identified.
- Affected individuals were homozygous for the WNT10A gene region.
- A novel homozygous missense mutation (c.392C>T; p.A131V) in exon 3 of WNT10A was identified in all affected individuals.
Conclusions:
- The study reports the first inherited missense mutation in WNT10A associated with OODD syndrome.
- This finding expands the known spectrum of WNT10A mutations and their clinical manifestations.
- The identified mutation provides new insights into the role of WNT10A in ectodermal development.
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