[P1-201] A novel CLN5 mutation in a Chinese late infantile neuronal ceroid lipofuscinosis family
Late infantile neuronal ceroid lipofuscinosis (LINCLs) is a childhood autosomal recessive hereditary disease characterized by accumulation of ceroid or lipofuscin-like autofluorescent materials in neurons and other cell types. There have been reports of several genes related to LINCLs, one of these genes, CLN5, a soluble lysosomal glycoprotein, results in variant forms of LINCLs (vLINCLs).
Here we report two siblings diagnosed with LINCLs born to non-consanguineous Chinese parents. The patients present with progressive decline in motor and cognitive functions, seizures, ataxia and intelligence retardation. Magnetic resonance imaging of the brain showed pronounced cerebellar atrophy. Electroencephalogram was abnormal. Electron microscopic examination of skin showed fingerprint bodies store in sweat gland epithelial cells. A whole genome sequencing, generated with DNA from the two patients and their parents, the patients contained a homozygous mutation: CLN5.c718 719delAT, p.Met240Valfs*13, and their parents are heterozygotes. This mutation has not been reported yet. CLN5.c718 719delAT is predicted to produce a frameshift mutation and premature stop codon resulting in a truncated protein. LINCLs is a rare disease besides in Finland, and there is no effective treatment exists at present. So prevention and early diagnosis is more crucial. Genetic testing is useful for definitive diagnosis. Our findings expand the mutation spectrum of CLN5 and enrich genotype–phenotype correlations. At the same time, it is helpful to study pathogenic mechanism of CLN5 mutation further.
Here we report two siblings diagnosed with LINCLs born to non-consanguineous Chinese parents. The patients present with progressive decline in motor and cognitive functions, seizures, ataxia and intelligence retardation. Magnetic resonance imaging of the brain showed pronounced cerebellar atrophy. Electroencephalogram was abnormal. Electron microscopic examination of skin showed fingerprint bodies store in sweat gland epithelial cells. A whole genome sequencing, generated with DNA from the two patients and their parents, the patients contained a homozygous mutation: CLN5.c718 719delAT, p.Met240Valfs*13, and their parents are heterozygotes. This mutation has not been reported yet. CLN5.c718 719delAT is predicted to produce a frameshift mutation and premature stop codon resulting in a truncated protein. LINCLs is a rare disease besides in Finland, and there is no effective treatment exists at present. So prevention and early diagnosis is more crucial. Genetic testing is useful for definitive diagnosis. Our findings expand the mutation spectrum of CLN5 and enrich genotype–phenotype correlations. At the same time, it is helpful to study pathogenic mechanism of CLN5 mutation further.