preprints.org > life sciences > genetics > doi: 10.20944/preprints202107.0661.v1

Preprint Case Report Version 1 Preserved in Portico This version is not peer-reviewed

Version 1 : Received: 27 July 2021 / Approved: 29 July 2021 / Online: 29 July 2021 (14:01:16 CEST)

We report diagnosis of Neuronal Ceroid Lipofuscinosis Type 2 (CLN2), a rare, hereditary neurodegenerative disease of childhood, in a four and a half year old girl, the first child of non-consanguineous parents with no family history. Despite extensive efforts by the parents, her clinical condition remained undiagnosed and without management, until recently. Our published “Bottom-up Approach”, based on comprehensive and multidisciplinary clinical, pathological, radiographical and genetic evaluations, played key role in diagnosis of the disease. Detailed analyses involving Next Generation Sequencing confirmed a missense variation NC_00011.10:g.6616374C>T (NP_000382.3:p.Arg339Gln; rs765380155) in exon 8 of TPP1 gene. In silico analyses predicted it to be highly pathogenic. Further family screening (including her both unaffected parents and asymptomatic, one year old younger sister) of the identified variation through Sanger Sequencing, revealed a perfect autosomal recessive segregation in the family. This study is the first case report on classic CLN2 from Jammu and Kashmir-India. This study is also indicating the effectiveness of our “Bottom-up Approach” in understanding rare disorders in low resource regions and the importance of timely diagnosis. Like in the proband, had diagnosis been established a bit early, the family might have benefitted at least with reference to their second child through counselling programmes.

CLN2; epilepsy; Jammu and Kashmir; loss of ambulation; neuronal ceroid lipofuscinoses type 2; neuroregression; seizures; TPP1

LIFE SCIENCES, Genetics