Premium
Association between a common missense variant in LOXL3 gene and the risk of non‐syndromic cleft palate
Author(s) -
Khan Mohammad Faisal J.,
Little Julian,
Mossey Peter A.,
SteegersTheunissen Régine P.M.,
Bonsi Martina,
Bassi Andreasi Rita,
Rubini Michele
Publication year - 2018
Publication title -
congenital anomalies
Language(s) - English
Resource type - Journals
eISSN - 1741-4520
pISSN - 0914-3505
DOI - 10.1111/cga.12288
Subject(s) - missense mutation , genetics , heterozygote advantage , genotype , penetrance , transmission disequilibrium test , biology , gene , medicine , mutation , single nucleotide polymorphism , phenotype
To investigate possible association between functional common variants in the lysyl oxidase like 3 gene and non‐syndromic cleft palate we selected a common missense variant p.Ile615Phe (rs17010021), which was predicted to have a probably damaging effect on the lysyl oxidase like 3 enzyme. We genotyped 258 non‐syndromic cleft palate case‐parent triads of European origin and tested genetic association using the transmission disequilibrium test and log‐linear regression analyses of genotypic relative risks and of parent‐of‐origin effects. The observed genotype frequency in parents was in Hardy–Weinberg equilibrium. Compared with wild‐type Ile/Ile homozygotes, the relative risks for Phe/Phe homozygote infants was 6.87 ( P value 3.0 × 10 −3 ), while that for Ile/Phe heterozygotes was not significant. Assuming an autosomal recessive model, the relative risks for Phe/Phe genotype resulted 10.54 ( P value 2.9 × 10 −5 ), with a 3.6% population attributable risk. No parent‐of‐origin effect was observed. The identification in lysyl oxidase like 3 of a missense variant which under a recessive model associates with 10‐fold increased risk of non‐syndromic cleft palate supports the hypothesis that the genetic etiology of this congenital anomaly includes relatively uncommon recessive variants with moderate penetrance and located in genes which are also involved in syndromes that include cleft palate as part of the phenotype. Our findings require functional validation and replication in a larger independent genetic association study.