Novel Mutation and Three Other Sequence Variants Segregating with Phenotype at Keratoconus 13q32 Susceptibility Locus

Overview

Journal Eur J Hum Genet

Specialty Genetics

Date 2011 Nov 3

PMID 22045297

Citations 39

Authors

Marta Czugala

Justyna A Karolak

Dorota M Nowak

Piotr Polakowski

Jose Pitarque

Andrea Molinari

Malgorzata Rydzanicz

Bassem A Bejjani

Beatrice Y J T Yue

Jacek P Szaflik

Marzena Gajecka

Affiliations

Soon will be listed here.

Abstract

Keratoconus (KTCN), a non-inflammatory corneal disorder characterized by stromal thinning, represents a major cause of corneal transplantations. Genetic and environmental factors have a role in the etiology of this complex disease. Previously reported linkage analysis revealed that chromosomal region 13q32 is likely to contain causative gene(s) for familial KTCN. Consequently, we have chosen eight positional candidate genes in this region: MBNL1, IPO5, FARP1, RNF113B, STK24, DOCK9, ZIC5 and ZIC2, and sequenced all of them in 51 individuals from Ecuadorian KTCN families and 105 matching controls. The mutation screening identified one mutation and three sequence variants showing 100% segregation under a dominant model with KTCN phenotype in one large Ecuadorian family. These substitutions were found in three different genes: c.2262A>C (p.Gln754His) and c.720+43A>G in DOCK9; c.2377-132A>C in IPO5 and c.1053+29G>C in STK24. PolyPhen analyses predicted that c.2262A>C (Gln754His) is possibly damaging for the protein function and structure. Our results suggest that c.2262A>C (p.Gln754His) mutation in DOCK9 may contribute to the KTCN phenotype in the large KTCN-014 family.

Citing Articles

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