Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy
Rev. invest. clín
;
73(3): 132-137, May.-Jun. 2021. graf
Artículo
en Inglés
|
LILACS-Express
| LILACS
| ID: biblio-1280449
ABSTRACT
ABSTRACT Background:
Fukuyama congenital muscular dystrophy (FCMD) is the most common form of a group of autosomal recessive disorders characterized by altered α-dystroglycan glycosylation and caused by FKTN gene mutations. However, mutations of this gene may cause a broad range of phenotypes, including Walker-Warburg syndrome, muscle-brain-eye disease, FCMD, limb-girdle muscular dystrophy without mental retardation, and cardiomyopathy with no or minimal skeletal muscle weakness.Objective:
Our purpose was to describe two siblings who died at a young age with dilated cardiomyopathy (DCM), no muscle weakness, or atrophy, and were homozygous for a FKTN missense mutation.Methods:
Site-directed next-generation sequencing (NGS) was performed. Pathogenicity of variants of interest was established according to the American College of Medical Genetics (ACMG) criteria, and all available first-degree relatives were screened for mutations by Sanger sequencing.Results:
NGS revealed a homozygous FKTN variant in the index case (p.Gly424Ser, rs752358445), classified as likely pathogenic by ACMG criteria. Both parents and an unaffected brother were heterozygous carriers. Since the siblings had no apparent skeletal muscle weakness or central nervous system involvement, FKTN mutations were not initially suspected.Conclusions:
This is the first report demonstrating that heterozygous individuals for the FKTN p.Gly424Ser mutation were healthy, while two homozygous brothers suffered severe DCM, strongly suggesting that this FKTN mutation is a rare cause of autosomal recessive DCM.
Texto completo:
Disponible
Índice:
LILACS (Américas)
País/Región como asunto:
México
Idioma:
Inglés
Revista:
Rev. invest. clín
Asunto de la revista:
Medicina
Año:
2021
Tipo del documento:
Artículo
País de afiliación:
México
Institución/País de afiliación:
Instituto Nacional de Cardiología Ignacio Chávez/MX
/
Instituto Nacional de Medicina Genómica/MX
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