First description of novel compound heterozygous mutations in HYCC1: clinical evaluations and molecular analysis in patient with hypomyelinating leukodystrophy-5 with retrospective view.

Hypomyelinating leukodystrophy-5 (HLD5) is a rare autosomal recessive hypomyelination disorder characterized by congenital cataract, progressive neurologic impairment, and myelin deficiency in the central and peripheral nervous system, caused by mutations in the HYCC1 gene. Here we report a 23-year-old girl with HLD5 from unrelated families. Molecular analysis was performed using sequence screening of the HYCC1 gene. In addition, in silico prediction tools and molecular investigation were used to predict the structural effect of the mutations. Results showed a novel compound heterozygous mutation in the HYCC1 gene. Moreover, in silico tools and 3D structural modeling revealed that c.521C > A (p.Ala174Glu) and c.652C > G (p.Gln218Glu) mutations could affect the structure, stability, and conformational analyses in the N-ter domain of the Hyccin protein. We also, we compared the phenotype of our patient with those of previously reported cases with HLD5 syndrome and our findings indicate the absence of reliable genotype-phenotype correlations. To the best of our knowledge, this is the first report describing a Tunisian HLD5 patient with compound heterozygous mutations (c.521C > A (p.Ala174Glu) and c.652C > G (p.Gln218Glu)) in HYCC1 gene.