Mutation Detection in Ceroid Lipofuscinoses Neuronal 2 (CLN2) Gene in Egyptian Patients

Abstract

Neuronal ceroid lipofuscinoses are the most common autosomal recessive neurodegenerative disorders in children, with a world-wide incidence ranges from 1:100.000 to 1:1.000.000 live births. More than 400 NCL mutations have been reported in 13 CLN genes, most of them have been related to classic and variant late infantile NCL. In the present study, mutation detection rate was as low as 23% (3/13 families). Mutation screening of the coding regions of 6 CLN genes (CLN1, CLN2, CLN3, CLN5, CLN6 and CLN8) of 17 patients from 13 families in Egypt revealed 3 different mutations (Q177R, R62C and I154del) in 4 patients; 2 were siblings, of Yemeni origin and 2 were unrelated Egyptian patients. Q177R located on exon 5 of CLN1 gene and detected in the two Yemeni siblings, patients (1&2) derived from family (F1). It was a novel missense mutation, that hasn't been reported in any of the available public databases (polyphene-2 program, dpSNAP, 1000genome project and SIFT functional analysis software). R62C and I154del are previously reported mutations in the CLN6 gene. R62C is a missense mutation, located on exon 2 and described in patient 3 from family (F2), while I154del is 3-bp deletion, located on exon 4 and described in patient 4 derived from families (F3).

Keywords: Neuronal ceroid lipofuscinoses(NCL), late infantile NCL, missense, deletion.