Association of IFT88 Gene Variants with Nonsyndromic Cleft Lip with or Without Cleft Palate

Overview

Journal Birth Defects Res

Specialties Reproductive Medicine
Toxicology

Date 2019 Apr 7

PMID 30953423

Citations 2

Authors

Amanda Barba

Christian Urbina

Lorena Maili

Matthew R Greives

Steven J Blackwell

John B Mulliken

Brett Chiquet

Susan H Blanton

Jacqueline T Hecht

Ariadne Letra

Affiliations

Soon will be listed here.

Abstract

Background: Nonsyndromic cleft lip with or without cleft palate (NSCLP) is a common birth defect with multifactorial etiology. Genetic studies have identified numerous gene variants in association with NSCLP. IFT88 (intraflagellar transport 88) has been suggested to play a major role in craniofacial development, as Ift88 mutant mice exhibit cleft palate and mutations in IFT88 were identified in individuals with NSCLP.

Objective: To investigate the association of IFT88 single nucleotide gene variants (SNVs) with NSCLP in a large family data set consisting of non-Hispanic white (NHW) and Hispanic families.

Methods: Nine SNVs in/nearby IFT88 were genotyped in 482 NHW families and 301 Hispanic NSCLP families. Genotyping was performed using TaqMan® chemistry. Single- and pairwise-SNV association analyses were performed for all families stratified by ethnicity and family history of NSCLP using the family-based association test (FBAT), and association in the presence of linkage (APL). Bonferroni correction was used to adjust for multiple testing and p values ≤.0055 were considered statistically significant.

Results: Significant association was found between IFT88 rs9509311 and rs2497490 and NSCLP in NHW all families (p = .004 and .005, respectively), while nominal associations were found for rs7998361 and rs9509307 (p < .05). Pairwise association analyses also showed nominal associations between NSCLP in both NHW and Hispanic data sets (p < .05). No association was found between individual variants in IFT88 and NSCLP in Hispanics.

Conclusions: Our results suggest that variation in IFT88 may contribute to NSCLP risk, particularly in multiplex families from a non-Hispanic white population.

Citing Articles

Ciliary and Non-Ciliary Roles of IFT88 in Development and Diseases.

Wang X, Yin G, Yang Y, Tian X Int J Mol Sci. 2025; 26(5).

PMID: 40076734 PMC: 11901018. DOI: 10.3390/ijms26052110.

Onodera S, Azuma T Int J Mol Sci. 2023; 24(16).

PMID: 37629084 PMC: 10454035. DOI: 10.3390/ijms241612903.

Evidence for craniofacial enhancer variation underlying nonsyndromic cleft lip and palate.

Morris V, Hashmi S, Zhu L, Maili L, Urbina C, Blackwell S Hum Genet. 2020; 139(10):1261-1272.

PMID: 32318854 PMC: 7487053. DOI: 10.1007/s00439-020-02169-9.

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