SCIENTIFIC ORGANIZATION:
Center for Brain Neurobiology and Neurogenetics, Institute of Cytology and Genetics, Siberian Branch of the Russian Academy of Sciences, Novosibirsk, Russia; Vavilov Institute of General Genetics of the Russian Academy of Sciences, Moscow, Russia; Department of Psychiatry, Brudnick Neuropsychiatric Research Institute, University of Massachusetts Medical School, Worcester, USA

REPORT FORM:
«Poster report»

AUTHOR(S)
OF THE REPORT:
Protasova M.S., Grigorenko A.P., Tyajelova T.V., Gusev F.E., Andreeva T.V., Reshetov D.A., Kuznetsova I.L., Klyushnikov S.N., Illarioshkin S.N., Rogaev E.I.

TALKING POINTS:

X-linked congenital cerebellar ataxia is a heterogeneous disease that occurs generally in newborn men and is characterized by developmental delay, difficulties in coordination resulted from hypoplasia of cerebellum. We examine 13 relatives from one large family from Eastern Russian province of Buryatia and 4 unrelated small families from other regions, previously described by S.N. Illarioshkin group. Genetic analysis was performed by whole genome Illumina high throughput sequencing and subsequent SNP and structural variation calling and annotation using GATK, SnpEff, Pindel tools. Missense mutation in ABCB7 gene on X-chromosome, resulted in a substitution of highly conserved Gly 682 to Ser, was identified in affected individuals. In addition we found a deletion of genomic region harboring portion of cooper-transporter ATP7A gene, including the region encoding the first metal-binding domain. Both mutations were confirmed to present in hemizygous state in all affected men of the Buryat family. We assume that abnormality in one of these genes or both these genes, which are closely linked on X-chromosome, leads ultimately to manifestation of the specific neurological phenotype in male carriers.

The work was supported by the Government of the Russian Federation (№ 14.B25.31.0033).