CRISPLD2 Variants Including a C471T Silent Mutation May Contribute to Nonsyndromic Cleft Lip With or Without Cleft Palate

Ariadne LETRA; Renato MENEZES; Eduardo E CASTILLA; Iêda M ORIOLI; Andrew E CZEIZEL; Lian Ma; Brett T CHIQUET; Jacqueline T HECHT; Alexandre R VIEIRA; Mary L MARAZITA; Margaret E COOPER; Renata F FONSECA; Stephen TROPP; Manika GOVIL; Jose M GRANJEIRO; Sandra R IMOEHL; M Adela Mansilla; Jeffrey C MURRAY

doi:10.1597/09-227

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CRISPLD2 Variants Including a C471T Silent Mutation May Contribute to Nonsyndromic Cleft Lip With or Without Cleft Palate

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CRISPLD2 Variants Including a C471T Silent Mutation May Contribute to Nonsyndromic Cleft Lip With or Without Cleft Palate

Ariadne LETRA, Renato MENEZES, Eduardo E CASTILLA, Iêda M ORIOLI, Andrew E CZEIZEL, Lian Ma, Brett T CHIQUET, Jacqueline T HECHT, Alexandre R VIEIRA, Mary L MARAZITA, …

The Cleft palate-craniofacial journal, Vol.48(4), pp.363-370

2011

DOI: 10.1597/09-227

PMCID: PMC3000893

PMID: 20815724

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https://www.ncbi.nlm.nih.gov/pmc/articles/3000893View

Open Access

Abstract

Objective To assess the association between nonsyndromic (NS) cleft lip with or without cleft palate (CL(P)) and single-nucleotide polymorphisms (SNPs) within the CRISPLD2 gene (cysteine-rich secretory protein LCCL domain containing 2). Design Four SNPs within the CRISPLD2 gene domain (rs1546124, rs8061351, rs2326398, rs4783099) were genotyped to test for association via family-based association methods. Participants A total of 5826 individuals from 1331 families in which one or more family member is affected with CL(P). Results Evidence of association was seen for SNP rs1546124 in U.S. (p = .02) and Brazilian (p = .04) Caucasian cohorts. We also found association of SNP rs1546124 with cleft palate alone (CP) in South Americans (Guatemala and ECLAMC) and combined Hispanics (Guatemala, ECLAMC, and Texas Hispanics; p = .03 for both comparisons) and with both cleft lip with cleft palate (CLP; p = .04) and CL(P) (p = .02) in North Americans. Strong evidence of association was found for SNP rs2326398 with CP in Asian populations (p = .003) and with CL(P) in Hispanics (p = .03) and also with bilateral CL(P) in Brazilians (p = .004). In Brazilians, SNP rs8061351 showed association with cleft subgroups incomplete CL(P) (p = .004) and unilateral incomplete CL(P) (p = .003). Prediction of SNP functionality revealed that the C allele in the C471T silent mutation (overrepresented in cases with CL(P) presents two putative exonic splicing enhancer motifs and creates a binding site AP-2 alpha, a transcription factor involved in craniofacial development. Conclusions Our results support the hypothesis that variants in the CRISPLD2 gene may be involved in the etiology of NS CL(P).

Biological and medical sciences

Medical sciences

Facial bones, jaws, teeth, parodontium: diseases, semeiology

Otorhinolaryngology. Stomatology

Non tumoral diseases

Details

Title: Subtitle: CRISPLD2 Variants Including a C471T Silent Mutation May Contribute to Nonsyndromic Cleft Lip With or Without Cleft Palate
Creators: Ariadne LETRA - Department of Oral Biology and Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Renato MENEZES - Department of Oral Biology and Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Eduardo E CASTILLA - Department of Genetics, FIOCRUZ, Rio de Janeiro, Brazil
Iêda M ORIOLI - Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Andrew E CZEIZEL - Foundation for the Community Control of Hereditary Diseases, Budapest, Hungary
Lian Ma - School of Stomatology, Beijing University, Beijing, China
Brett T CHIQUET - Department of Pediatrics and Pediatric Research Center, University of Texas Medical School, Houston, Texas, United States
Jacqueline T HECHT - Department of Pediatrics and Pediatric Research Center, University of Texas Medical School, Houston, Texas, United States
Alexandre R VIEIRA - Department of Oral Biology, Center for Craniofacial and Dental Genetics, and Department of Pediatric Dentistry, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Mary L MARAZITA - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine; Department of Human Genetics, Graduate School of Public Health; and Department of Psychiatry and Clinical and Translational Sciences Institute, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Margaret E COOPER - Department of Oral Biology and Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Renata F FONSECA - Department of Genetics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil
Stephen TROPP - Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Manika GOVIL - Department of Oral Biology and Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States
Jose M GRANJEIRO - Department of Cell and Molecular Biology, Universidade Federal Fluminense, Niterói, Brazil
Sandra R IMOEHL - College of Dentistry, University of Iowa, Iowa City, Iowa, United States
M Adela Mansilla - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Jeffrey C MURRAY - Department of Pediatrics, University of Iowa, Iowa City, Iowa, United States
Resource Type: Journal article
Publication Details: The Cleft palate-craniofacial journal, Vol.48(4), pp.363-370
DOI: 10.1597/09-227
PMID: 20815724
PMCID: PMC3000893
NLM abbreviation: Cleft Palate Craniofac J
ISSN: 1055-6656
eISSN: 1545-1569
Publisher: American Cleft Palate-Craniofacial Association; Chapel Hill, NC
Language: English
Date published: 2011
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Iowa Institute of Human Genetics
Record Identifier: 9984025416302771

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