We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
Neuronal ceroid lipofuscinosis in the Russian population: Two novel mutations and the prevalence of heterozygous carriers.
- Authors
Kozina, Anastasiya A.; Okuneva, Elena G.; Baryshnikova, Natalia V.; Kondakova, Olga B.; Nikolaeva, Ekaterina A.; Fedoniuk, Inessa D.; Mikhailova, Svetlana V.; Krasnenko, Anna Y.; Stetsenko, Ivan F.; Plotnikov, Nikolay A.; Klimchuk, Olesia I.; Popov, Yaroslav V.; Surkova, Ekaterina I.; Shatalov, Peter A.; Rakitko, Alexander S.; Ilinsky, Valery V.
- Abstract
Background: Neuronal ceroid lipofuscinoses (NCLs) are a group of neurodegenerative disorders characterized by an accumulation of lipofuscin in the body's tissues. NCLs are associated with variable age of onset and progressive symptoms including seizures, psychomotor decline, and loss of vision. Methods: We describe the clinical and molecular characteristics of four Russian patients with NCL (one female and three males, with ages ranging from 4 to 5 years). The clinical features of these patients include cognitive and motor deterioration, seizures, stereotypies, and magnetic resonance imaging signs of brain atrophy. Exome sequencing was performed to identify the genetic variants of patients with NCL. Additionally, we tested 6,396 healthy Russians for NCL alleles. Results: We identified five distinct mutations in four NCL‐associated genes of which two mutations are novel. These include a novel homozygous frameshift mutation in the CLN6 gene, a compound heterozygous missense mutation in the KCTD7 gene, and previously known mutations in KCTD7, TPP1, and MFSD8 genes. Furthermore, we estimated the Russian population carrier frequency of pathogenic and likely pathogenic variants in 13 genes associated with different types of NCL. Conclusion: Our study expands the spectrum of mutations in lipofuscinosis. This is the first study to describe the molecular basis of NCLs in Russia and has profound and numerous clinical implications for diagnosis, genetic counseling, genotype–phenotype correlations, and prognosis.
- Subjects
RUSSIA; NEURONAL ceroid-lipofuscinosis; GENETIC mutation; FRAMESHIFT mutation; GENETIC counseling; CEREBRAL atrophy; RECESSIVE genes; DISEASE vectors
- Publication
Molecular Genetics & Genomic Medicine, 2020, Vol 8, Issue 7, p1
- ISSN
2324-9269
- Publication type
Academic Journal
- DOI
10.1002/mgg3.1228