CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate

Ariadne Letra, Renato Menezes, Margaret E. Cooper, Renata F. Fonseca, Stephen Tropp, Manika Govil, Jose M. Granjeiro, Sandra R. Imoehl, M. Adela Mansilla, Jeffrey C. Murray, Eduardo E. Castilla, Iêda M. Orioli, E. Czeizel, Lian Ma, Brett T. Chiquet, Jacqueline T. Hecht, Alexandre R. Vieira, Mary L. Marazita

Research output: Contribution to journalArticle

19 Citations (Scopus)

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).

Original languageEnglish
Pages (from-to)363-370
Number of pages8
JournalCleft Palate-Craniofacial Journal
Volume48
Issue number4
DOIs
Publication statusPublished - Jul 2011

Fingerprint

Cleft Lip
Cleft Palate
Single Nucleotide Polymorphism
Hispanic Americans
Guatemala
Silent Mutation
Genes
Cysteine
Transcription Factors
Alleles
Binding Sites

Keywords

  • Cleft lip
  • Cleft palate
  • CRISPLD2 gene
  • Subphenotypes

ASJC Scopus subject areas

  • Otorhinolaryngology
  • Oral Surgery

Cite this

Letra, A., Menezes, R., Cooper, M. E., Fonseca, R. F., Tropp, S., Govil, M., ... Marazita, M. L. (2011). CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. Cleft Palate-Craniofacial Journal, 48(4), 363-370. https://doi.org/10.1597/09-227

CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. / Letra, Ariadne; Menezes, Renato; Cooper, Margaret E.; Fonseca, Renata F.; Tropp, Stephen; Govil, Manika; Granjeiro, Jose M.; Imoehl, Sandra R.; Mansilla, M. Adela; Murray, Jeffrey C.; Castilla, Eduardo E.; Orioli, Iêda M.; Czeizel, E.; Ma, Lian; Chiquet, Brett T.; Hecht, Jacqueline T.; Vieira, Alexandre R.; Marazita, Mary L.

In: Cleft Palate-Craniofacial Journal, Vol. 48, No. 4, 07.2011, p. 363-370.

Research output: Contribution to journalArticle

Letra, A, Menezes, R, Cooper, ME, Fonseca, RF, Tropp, S, Govil, M, Granjeiro, JM, Imoehl, SR, Mansilla, MA, Murray, JC, Castilla, EE, Orioli, IM, Czeizel, E, Ma, L, Chiquet, BT, Hecht, JT, Vieira, AR & Marazita, ML 2011, 'CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate', Cleft Palate-Craniofacial Journal, vol. 48, no. 4, pp. 363-370. https://doi.org/10.1597/09-227
Letra, Ariadne ; Menezes, Renato ; Cooper, Margaret E. ; Fonseca, Renata F. ; Tropp, Stephen ; Govil, Manika ; Granjeiro, Jose M. ; Imoehl, Sandra R. ; Mansilla, M. Adela ; Murray, Jeffrey C. ; Castilla, Eduardo E. ; Orioli, Iêda M. ; Czeizel, E. ; Ma, Lian ; Chiquet, Brett T. ; Hecht, Jacqueline T. ; Vieira, Alexandre R. ; Marazita, Mary L. / CRISPLD2 variants including a C471T silent mutation may contribute to nonsyndromic cleft lip with or without cleft palate. In: Cleft Palate-Craniofacial Journal. 2011 ; Vol. 48, No. 4. pp. 363-370.
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AU - Letra, Ariadne

AU - Menezes, Renato

AU - Cooper, Margaret E.

AU - Fonseca, Renata F.

AU - Tropp, Stephen

AU - Govil, Manika

AU - Granjeiro, Jose M.

AU - Imoehl, Sandra R.

AU - Mansilla, M. Adela

AU - Murray, Jeffrey C.

AU - Castilla, Eduardo E.

AU - Orioli, Iêda M.

AU - Czeizel, E.

AU - Ma, Lian

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