Journal article
Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?
American journal of medical genetics. Part A, Vol.191(10), pp.2558-2570
10/2023
DOI: 10.1002/ajmg.a.63336
PMCID: PMC10528230
PMID: 37350193
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.
Details
- Title: Subtitle
- Rare variants found in multiplex families with orofacial clefts: Does expanding the phenotype make a difference?
- Creators
- Kimberly K Diaz Perez - Emory University School of MedicineSydney Chung - Emory UniversityS Taylor Head - Emory UniversityMichael P Epstein - Emory UniversityJacqueline T Hecht - The University of Texas Health Science CenterGeorge L Wehby - University of IowaSeth M Weinberg - University of PittsburghJeffrey C Murray - University of IowaMary L Marazita - University of PittsburghElizabeth J Leslie - Emory University
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.191(10), pp.2558-2570
- DOI
- 10.1002/ajmg.a.63336
- PMID
- 37350193
- PMCID
- PMC10528230
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Grant note
- Howard Hughes Medical Institute NIH HHS
- Language
- English
- Electronic publication date
- 06/23/2023
- Date published
- 10/2023
- Academic Unit
- Preventive and Community Dentistry; Anatomy and Cell Biology; Health Management and Policy; Stead Family Department of Pediatrics; Epidemiology; Economics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984438859102771
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