title: Segregation of Incomplete Achromatopsia and Alopecia Due to PDE6H and LPAR6 Variants in a Consanguineous Family from Pakistan.
abstract: 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.
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. p.j.c.ramane@medisin.uio.no.|Faculty of Medicine, University of Oslo, Oslo 0316, Norway. p.j.c.ramane@medisin.uio.no.
authors.forename: Christeen Ramane J
authors.initials: CR
authors.lastname: Pedurupillay
authors.affiliation: Department of Ophthalmology, Oslo University Hospital, Oslo 0450, Norway. erllan@ous-hf.no.
authors.forename: Erlend Christoffer Sommer
authors.initials: EC
authors.lastname: Landsend
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. magnusdv@medisin.uio.no.
authors.forename: Magnus Dehli
authors.initials: MD
authors.lastname: Vigeland
authors.affiliation: Department of Genetic Medicine and Development, University of Geneva, Geneva 1211, Switzerland. Muhammad.Ansar@unige.ch.
authors.forename: Muhammad
authors.initials: M
authors.lastname: Ansar
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. eirik.frengen@medisin.uio.no.|Faculty of Medicine, University of Oslo, Oslo 0316, Norway. eirik.frengen@medisin.uio.no.
authors.forename: Eirik
authors.initials: E
authors.lastname: Frengen
authors.affiliation: Department of Medical Genetics, Oslo University Hospital, Oslo 0450, Norway. doriana.misceo@medisin.uio.no.|Faculty of Medicine, University of Oslo, Oslo 0316, Norway. doriana.misceo@medisin.uio.no.
authors.forename: Doriana
authors.initials: D
authors.lastname: Misceo
authors.affiliation: Faculty of Medicine, University of Oslo, Oslo 0316, Norway. petter.stromme@medisin.uio.no.|Women and Children's Division, Department of Clinical Neurosciences for Children, Oslo University Hospital, Oslo 0450, Norway. petter.stromme@medisin.uio.no.
authors.forename: Petter
authors.initials: P
authors.lastname: Strømme
keywords: LPAR6; PDE6H; achromatopsia; alopecia; phosphodiesterase (PDE)