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Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan

We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the vari...

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Autores principales: Pedurupillay, Christeen Ramane J., Landsend, Erlend Christoffer Sommer, Vigeland, Magnus Dehli, Ansar, Muhammad, Frengen, Eirik, Misceo, Doriana, Strømme, Petter
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999829/
https://www.ncbi.nlm.nih.gov/pubmed/27472364
http://dx.doi.org/10.3390/genes7080041
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author Pedurupillay, Christeen Ramane J.
Landsend, Erlend Christoffer Sommer
Vigeland, Magnus Dehli
Ansar, Muhammad
Frengen, Eirik
Misceo, Doriana
Strømme, Petter
author_facet Pedurupillay, Christeen Ramane J.
Landsend, Erlend Christoffer Sommer
Vigeland, Magnus Dehli
Ansar, Muhammad
Frengen, Eirik
Misceo, Doriana
Strømme, Petter
author_sort Pedurupillay, Christeen Ramane J.
collection PubMed
description We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan.
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spelling pubmed-49998292016-09-01 Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan Pedurupillay, Christeen Ramane J. Landsend, Erlend Christoffer Sommer Vigeland, Magnus Dehli Ansar, Muhammad Frengen, Eirik Misceo, Doriana Strømme, Petter Genes (Basel) Case Report We report on two brothers with visual impairment, and non-syndromic alopecia in the elder proband. The parents were first-degree Pakistani cousins. Whole exome sequencing of the elder brother and parents, followed by Sanger sequencing of all four family members, led to the identification of the variants responsible for the two phenotypes. One variant was a homozygous nonsense variant in the inhibitory subunit of the cone-specific cGMP phosphodiesterase gene, PDE6H:c.35C>G (p.Ser12*). PDE6H is expressed in the cones of the retina, which are involved in perception of color vision. This is the second report of a homozygous PDE6H:c.35C>G variant causing incomplete achromatopsia (OMIM 610024), thus strongly supporting the hypothesis that loss-of-function variants in PDE6H cause this visual deficiency phenotype. The second variant was a homozygous missense substitution in the lysophosphatidic acid receptor 6, LPAR6:c.188A>T (p.Asp63Val). LPAR6 acts as a G-protein-coupled receptor involved in hair growth. Biallelic loss-of-function variants in LPAR6 cause hypotrichosis type 8 (OMIM 278150), with or without woolly hair, a form of non-syndromic alopecia. Biallelic LPAR6:c.188A>T was previously described in five families from Pakistan. MDPI 2016-07-27 /pmc/articles/PMC4999829/ /pubmed/27472364 http://dx.doi.org/10.3390/genes7080041 Text en © 2016 by the authors; licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC-BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Case Report
Pedurupillay, Christeen Ramane J.
Landsend, Erlend Christoffer Sommer
Vigeland, Magnus Dehli
Ansar, Muhammad
Frengen, Eirik
Misceo, Doriana
Strømme, Petter
Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title_full Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title_fullStr Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title_full_unstemmed Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title_short Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan
title_sort segregation of incomplete achromatopsia and alopecia due to pde6h and lpar6 variants in a consanguineous family from pakistan
topic Case Report
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4999829/
https://www.ncbi.nlm.nih.gov/pubmed/27472364
http://dx.doi.org/10.3390/genes7080041
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