Faculty, Staff and Student Publications
Language
English
Publication Date
10-1-2023
Journal
American Journal of Medical Genetics Part A
DOI
10.1002/ajmg.a.63336
PMID
37350193
PMCID
PMC10528230
PubMedCentral® Posted Date
10-1-2024
PubMedCentral® Full Text Version
Author MSS
Abstract
Exome sequencing (ES) is now a relatively straightforward process to identify causal variants in Mendelian disorders. However, the same is not true for ES in families where the inheritance patterns are less clear, and a complex etiology is suspected. Orofacial clefts (OFCs) are highly heritable birth defects with both Mendelian and complex etiologies. The phenotypic spectrum of OFCs may include overt clefts and several subclinical phenotypes, such as discontinuities in the orbicularis oris muscle (OOM) in the upper lip, velopharyngeal insufficiency (VPI), microform clefts or bifid uvulas. We hypothesize that expanding the OFC phenotype to include these phenotypes can clarify inheritance patterns in multiplex families, making them appear more Mendelian. We performed exome sequencing to find rare, likely causal genetic variants in 31 multiplex OFC families, which included families with multiple individuals with OFCs and individuals with subclinical phenotypes. We identified likely causal variants in COL11A2, IRF6, SHROOM3, SMC3, TBX3, and TP63 in six families. Although we did not find clear evidence supporting the subclinical phenotype hypothesis, our findings support a role for rare variants in the etiology of OFCs.
Keywords
Humans, Cleft Palate, Cleft Lip, Phenotype, Exome Sequencing, Interferon Regulatory Factors
Published Open-Access
yes
Recommended Citation
Diaz Perez, Kimberly K; Chung, Sydney; Head, S Taylor; et al., "Rare Variants Found in Multiplex Families With Orofacial Clefts: Does Expanding the Phenotype Make a Difference?" (2023). Faculty, Staff and Student Publications. 4181.
https://digitalcommons.library.tmc.edu/uthmed_docs/4181