Clinico- investigative profile of 7 genetically confirmed cases of neuronal ceroid lipofuscinosis: Indian perspective

Abstract

To describe a cohort of genetically confirmed Neuronal Ceroid Lipofuscinoses (NCL) from a tertiary-care institute from India. A retrospective study on genetically confirmed NCL's (2017–2019). A total of 7 patients were classified into 5 subgroups based on protein and gene defect. CLN7-NCL = 2 patients, mean age of onset 3.5 years, both males, clinically had developmental delay and regression following a febrile illness. One patient had spasmus nutans and bulls eye maculopathy. Homozygous 5′ splice site variation in intron 9, c.863 + 1G > A (5′ splice site) of the MFSD8 gene(chr4:128854139C > T) was detected in one patient and deletion of exon 1 to 3 in MFSD8 gene in the other. CLN6-NCL = 2 patients, mean age of onset 9.5 years, M:F = 1:1, had developmental delay, seizures and progressive extrapyramidal manifestations. Homozygous mutations in CLN6 gene at Exon 4 c.425A > G(p.Tyr142Cys); and Exon 2 c.103G > A(p.Asp35Asn) respectively. CLN1-NCL = 1 patient, age of onset 1.5 years boy, had developmental delay, regression, hypertonia and retinitis pigmentosa. Neuroimaging showed diffuse cortical atrophy. Compound heterozygous mutations in PPT1 gene at Exon 7 c.674 T > C(p.Phe225Ser) and Exon 7 c.651_671 del(p.Asn218_Lys224del) was present. CLN3-NCL = 1, age of onset 8 years, male, had progressive vision loss, cognitive decline with autistic features. Neuroimaging showed cerebellar and cerebral atrophy. Compound heterozygous mutations noted in Intron 9 c.534-2A > G(splice site) and Exon 10 c.565G > T(p.Gly189Trp) of CLN3 gene respectively. CLN8 = 1, age of onset 5 years with regression, cerebellar and visual symptoms, genetically had homozygous mutation in CLN8 gene[c.208C > T(p.Arg70Cys)]. This study describes a cohort of genetically confirmed NCL's from our centre and demonstrates the genetic heterogeneity.