A novel MFSD8 mutation in a Russian patient with neuronal ceroid lipofuscinosis type 7: a case report

BMC Medical Genetics
Anastasiya Aleksandrovna KozinaValery Vladimirovich Ilinsky

Abstract

Neuronal ceroid lipofuscinoses (NCLs) are the most common autosomal recessive neurodegenerative disorders in children. Clinical manifestations include progressive cognitive decline, motor impairment, ataxia, visual loss, seizures and early death. To date more than 440 NCL-causing mutations in 13 genes are known. We report clinical and genetic characteristics of a 5-year-old girl affected by ceroid lipofuscinosis type 7 (NCL7). She had progressive motor and mental deterioration since the age of 2,5 years. Later she developed progressive vision loss, stereotypies, action myoclonus and epilepsy. By the age of 5 years she stopped walking. Based on symptoms, diagnosis of Rett syndrome was suggested, but no abnormalities were detected in MeCP2. We identified a novel homozygous mutation in MFSD8 gene (c.525 T > A, p.Cys175Ter). To our knowledge, this is the first report of MFSD8 gene mutation in a Russian patient with variant late-infantile NCL. Our results enlarge mutational spectrum of ceroid lipofuscinosis type 7 and demonstrate tremendous diagnosis value of exome sequencing for pediatric NCLs. Also we confirmed that NCL should be suspected in patients with Rett-like phenotype at onset and negative MECP2 mutation.

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Citations

Apr 23, 2019·Ophthalmic Genetics·Davood Zare-AbdollahiHamid Reza Khorram Khorshid
May 16, 2020·Molecular Genetics & Genomic Medicine·Anastasiya A KozinaValery V Ilinsky
Jan 22, 2021·BMJ Case Reports·Bhanudeep SinganamallaNaveen Sankhyan

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Methods Mentioned

BETA
exome sequencing

Software Mentioned

Clinvar
ExAC
PolyPhen
snpEff
1000 Genomes Browser
SIFT
Cutadapt
GATK
BWA MEM
GATK HaplotypeCaller

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