Rare Variants in the Epithelial Cadherin Gene Underlying the Genetic Etiology of Nonsyndromic Cleft Lip with or without Cleft Palate

2015 ◽  
Vol 36 (11) ◽  
pp. 1029-1033 ◽  
Author(s):  
Luciano Abreu Brito ◽  
Guilherme Lopes Yamamoto ◽  
Soraia Melo ◽  
Carolina Malcher ◽  
Simone Gomes Ferreira ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Rare Variants ◽  
Genetic Etiology ◽  
Epithelial Cadherin

SUMO1 as a candidate gene for non-syndromic cleft lip with or without cleft palate: No evidence for the involvement of common or rare variants in Central European patients

2011 ◽  
Vol 75 (1) ◽  
pp. 49-52 ◽  
Author(s):  
Nilma Almeida de Assis ◽  
Stefanie Nowak ◽  
Kerstin U. Ludwig ◽  
Heiko Reutter ◽  
Jennifer Vollmer ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Candidate Gene ◽  
Cleft Lip ◽  
Rare Variants ◽  
Central European

scholarly journals Mutations in the Epithelial Cadherin-p120-Catenin Complex Cause Mendelian Non-Syndromic Cleft Lip with or without Cleft Palate

2018 ◽  
Vol 102 (6) ◽  
pp. 1143-1157 ◽  
Author(s):  
Liza L. Cox ◽  
Timothy C. Cox ◽  
Lina M. Moreno Uribe ◽  
Ying Zhu ◽  
Chika T. Richter ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
P120 Catenin ◽  
Epithelial Cadherin

scholarly journals Loss-of-Function GRHL3 Variants Detected in African Patients with Isolated Cleft Palate

2017 ◽  
Vol 97 (1) ◽  
pp. 41-48 ◽  
Author(s):  
M.A. Eshete ◽  
H. Liu ◽  
M. Li ◽  
W.L. Adeyemo ◽  
L.J.J Gowans ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
De Novo ◽  
Phosphorylation Site ◽  
Dominant Negative ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Sumoylation Site ◽  
Genetic Etiology

In contrast to the progress that has been made toward understanding the genetic etiology of cleft lip with or without cleft palate, relatively little is known about the genetic etiology for cleft palate only (CPO). A common coding variant of grainyhead like transcription factor 3 ( GRHL3) was recently shown to be associated with risk for CPO in Europeans. Mutations in this gene were also reported in families with Van der Woude syndrome. To identify rare mutations in GRHL3 that might explain the missing heritability for CPO, we sequenced GRHL3 in cases of CPO from Africa. We recruited participants from Ghana, Ethiopia, and Nigeria. This cohort included case-parent trios, cases and other family members, as well as controls. We sequenced exons of this gene in DNA from a total of 134 nonsyndromic cases. When possible, we sequenced them in parents to identify de novo mutations. Five novel mutations were identified: 2 missense (c.497C>A; p.Pro166His and c.1229A>G; p.Asp410Gly), 1 splice site (c.1282A>C p.Ser428Arg), 1 frameshift (c.470delC; p.Gly158Alafster55), and 1 nonsense (c.1677C>A; p.Tyr559Ter). These mutations were absent from 270 sequenced controls and from all public exome and whole genome databases, including the 1000 Genomes database (which includes data from Africa). However, 4 of the 5 mutations were present in unaffected mothers, indicating that their penetrance is incomplete. Interestingly, 1 mutation damaged a predicted sumoylation site, and another disrupted a predicted CK1 phosphorylation site. Overexpression assays in zebrafish and reporter assays in vitro indicated that 4 variants were functionally null or hypomorphic, while 1 was dominant negative. This study provides evidence that, as in Caucasian populations, mutations in GRHL3 contribute to the risk of nonsyndromic CPO in the African population.

scholarly journals Genetic etiology of cleft lip and cleft palate

2020 ◽  
Vol 7 (4) ◽  
pp. 328-348
Author(s):  
AN Mahamad Irfanulla Khan ◽  
◽  
CS Prashanth ◽  
N Srinath ◽  
◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Genetic Etiology

22q11.2 Deletion Syndrome in Colombian Patients With Syndromic Cleft Lip and/or Palate

2018 ◽  
Vol 56 (1) ◽  
pp. 116-122 ◽  
Author(s):  
Suleima Carpeta ◽  
Tatiana Pineda ◽  
Maria Claudia Martínez ◽  
Gloria Osorio ◽  
Gloria Liliana Porras-Hurtado ◽  
...  
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Chromosomal Abnormalities ◽  
22Q11.2 Deletion Syndrome ◽  
Clinical Findings ◽  
Deletion Syndrome ◽  
Chromosomal Deletion ◽  
Genetic Etiology ◽  
22Q11.2 Deletion ◽  
Dependent Probe

The objective of this work was to identify 22q11.2 chromosomal deletion in patients with cleft lip and/or cleft palate and suggestive syndromic phenotype in Colombian patients. We studied 49 patients with cleft lip and/or cleft palate, exhibiting additional clinical findings linked to 22q11.2 deletion syndrome. All patients underwent high-resolution G-banded karyotyping, multiplex ligation-dependent probe amplification, and clinical evaluation by a geneticist. Seven patients presented 22q11.2 deletion and 2 patients had other chromosomal abnormalities. In conclusion, this study contributes with new data for genetic etiology in syndromic conditions of oral fissures.

scholarly journals Accumulation of Rare Coding Variants in Genes Implicated in Risk of Human Cleft Lip with or without Cleft Palate

2019 ◽  
Author(s):  
Nicholas J. Marini ◽  
Kripa Asrani ◽  
Wei Yang ◽  
Jasper Rine ◽  
Gary M Shaw
Keyword(s):  
Cleft Palate ◽  
Cleft Lip ◽  
Rare Variants ◽  
Fold Increase ◽  
Loss Of Function ◽  
Craniofacial Malformation ◽  
Gene Level ◽  
Multiple Case ◽  
Genetic And Environmental Factors ◽  
Coding Variants

ABSTRACTCleft lip with/without cleft palate (CLP) is a common craniofacial malformation with complex etiologies, reflecting both genetic and environmental factors. Most of the suspected genetic risk for CLP has yet to be identified. To further classify risk loci and estimate the contribution of rare variants, we sequenced the exons in 49 candidate genes in 323 CLP cases and 211 non-malformed controls. Our findings indicated that rare, protein-altering variants displayed markedly higher burdens in CLP cases at relevant loci. First, putative loss-of-function mutations (nonsense, frameshift) were significantly enriched among cases: 13 of 323 cases (~4%) harbored such alleles within these 49 genes, versus one such change in controls (p = 0.01). Second, in gene-level analyses, the burden of rare alleles showed greater case-association for several genes previously implicated in cleft risk. For example, BHMT displayed a 10-fold increase in protein-altering variants in CLP cases (p = 0.03), including multiple case occurrences of a rare frameshift mutation (K400fs). Other loci with greater rare, coding allele burdens in cases were in signaling pathways relevant to craniofacial development (WNT9B, BMP4, BMPR1B) as well as the methionine cycle (MTRR). We conclude that rare coding variants may confer risk for isolated CLP.

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