Journal article
A Novel Mutation in FOXC1 in a Lebanese Family with Congenital Heart Disease and Anterior Segment Dysgenesis: Potential Roles for NFATC1 and DPT in the Phenotypic Variations
Frontiers in cardiovascular medicine, Vol.4, pp.58-58
09/20/2017
DOI: 10.3389/fcvm.2017.00058
PMCID: PMC5611365
PMID: 28979898
Abstract
Congenital heart diseases (CHDs) are still the leading cause of death in neonates. Anterior segment dysgenesis is a broad clinical phenotype that affects the normal development of the eye, leading in most of the cases to glaucoma which is still a major cause of blindness for children and adolescents. Despite tremendous insights gained from genetic studies, a clear genotype–phenotype correlation is still difficult to draw. In Lebanon, a small country with still a high rate of consanguineous marriages, there are little data on the epidemiology of glaucoma amongst children with or without CHD. We carried out whole exome sequencing (WES) on a family with anterior segment dysgenesis, and CHD composed of three affected children with glaucoma, two of them with structural cardiac defects and three healthy siblings. The results unravel a novel mutation in
FOXC1
(p. R127H) segregating with the phenotype and inherited from the mother, who did not develop glaucoma. We propose a digenic model for glaucoma in this family by combining the
FOXC1
variant with a missense variant inherited from the father in the dermatopontin (
DPT
) gene. We also unravel a novel
NFATC1
missense mutation predicted to be deleterious and present only in the patient with a severe ocular and cardiac phenotype. This is the first report on
FOXC1
using WES to genetically characterize a family with both ocular and cardiac malformations. Our results support the usage of such technology to have a better genotype–phenotype picture for Mendelian-inherited diseases for which expressivity and penetrance are still not answered.
Details
- Title: Subtitle
- A Novel Mutation in FOXC1 in a Lebanese Family with Congenital Heart Disease and Anterior Segment Dysgenesis: Potential Roles for NFATC1 and DPT in the Phenotypic Variations
- Creators
- Athar Khalil - American University of BeirutChristiane Al-Haddad - , , , , , , , , , ,Hadla Hariri - American University of BeirutKamel Shibbani - American University of BeirutFadi Bitar - American University of BeirutMazen Kurban - Columbia UniversityGeorges Nemer - American University of BeirutMariam Arabi - American University of Beirut
- Resource Type
- Journal article
- Publication Details
- Frontiers in cardiovascular medicine, Vol.4, pp.58-58
- Publisher
- Frontiers Media S.A
- DOI
- 10.3389/fcvm.2017.00058
- PMID
- 28979898
- PMCID
- PMC5611365
- ISSN
- 2297-055X
- eISSN
- 2297-055X
- Language
- English
- Date published
- 09/20/2017
- Academic Unit
- Cardiology; Stead Family Department of Pediatrics
- Record Identifier
- 9984702825702771
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