Novel mutation in the fukutin gene in an Egyptian family with Fukuyama congenital muscular dystrophy and microcephaly

Ismail, Samira; Schaffer, Ashleigh E.; Rosti, Rasim Özgür; Gleeson, Joseph G.; Zaki, Maha S.

doi:10.1016/j.gene.2014.01.070

Cited by 6 publications

(3 citation statements)

References 31 publications

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“…It should be pointed out that we found 2 human orthologs, FCMD and KLF8 , of the common regulators LEU3 and SUM1 respectively, associated with human disorders. The protein encoded by FCMD gene regulates the migration and assembly of neurons during cortical histogenesis, and mutations in this gene may lead to Fukuyama congenital muscular dystrophy [42] . Abnormal expression of the KLF8 has been implicated in mental retardation [43] .…”

Section: Resultsmentioning

confidence: 99%

Global Genetic Determinants of Mitochondrial DNA Copy Number

Zhang

Singh

2014

PLoS ONE

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Many human diseases including development of cancer is associated with depletion of mitochondrial DNA (mtDNA) content. These diseases are collectively described as mitochondrial DNA depletion syndrome (MDS). High similarity between yeast and human mitochondria allows genomic study of the budding yeast to be used to identify human disease genes. In this study, we systematically screened the pre-existing respiratory-deficient Saccharomyces cerevisiae yeast strains using fluorescent microscopy and identified 102 nuclear genes whose deletions result in a complete mtDNA loss, of which 52 are not reported previously. Strikingly, these genes mainly encode protein products involved in mitochondrial protein biosynthesis process (54.9%). The rest of these genes either encode protein products associated with nucleic acid metabolism (14.7%), oxidative phosphorylation (3.9%), or other protein products (13.7%) responsible for bud-site selection, mitochondrial intermembrane space protein import, assembly of cytochrome-c oxidase, vacuolar protein sorting, protein-nucleus import, calcium-mediated signaling, heme biosynthesis and iron homeostasis. Thirteen (12.7%) of the genes encode proteins of unknown function. We identified human orthologs of these genes, conducted the interaction between the gene products and linked them to human mitochondrial disorders and other pathologies. In addition, we screened for genes whose defects affect the nuclear genome integrity. Our data provide a systematic view of the nuclear genes involved in maintenance of mitochondrial DNA. Together, our studies i) provide a global view of the genes regulating mtDNA content; ii) provide compelling new evidence toward understanding novel mechanism involved in mitochondrial genome maintenance and iii) provide useful clues in understanding human diseases in which mitochondrial defect and in particular depletion of mitochondrial genome plays a critical role.

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Section: Resultsmentioning

confidence: 99%

Global Genetic Determinants of Mitochondrial DNA Copy Number

Zhang

Singh

2014

PLoS ONE

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“…On the other hand, although the molecular mechanisms of FKTN mutations associated with DCM are unclear, fukutin function may be partially preserved in skeletal muscle of patients with minimal or late-onset muscle weakness. Further analyses are needed to clarify the function of fukutin in the glycosylation of α-DG in different organs 6,2,10,11,17 .…”

Section: Discussionmentioning

confidence: 99%

“…FCMD is also a severe phenotype with severe congenital muscle wasting, structural brain alterations, cognitive impairment, and epilepsy. The clinical course is helplessly progressive, and death occurs at an average age of 16 years 2,3 . Limb-girdle muscular dystrophy without cognitive impairment is milder 4 , and cardiomyopathy with no or minimal skeletal muscle weakness is the mildest phenotype 5,6 .…”

Section: Introductionmentioning

confidence: 99%

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy

Villarreal-Molina

Rosas-Madrigal

López-Mora

et al. 2021

RIC

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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, limbgirdle 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.

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Mutations in genes associated with either myopathy or noncompaction

Finsterer

Stöllberger

2018

Herz

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Novel mutation in the fukutin gene in an Egyptian family with Fukuyama congenital muscular dystrophy and microcephaly

Cited by 6 publications

References 31 publications

Global Genetic Determinants of Mitochondrial DNA Copy Number

Global Genetic Determinants of Mitochondrial DNA Copy Number

Homozygous Fukutin Missense Mutation in Two Mexican Siblings with Dilated Cardiomyopathy

Mutations in genes associated with either myopathy or noncompaction

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