J Pediatr Genet 2019; 08(02): 058-062
DOI: 10.1055/s-0039-1684008
Original Article
Georg Thieme Verlag KG Stuttgart · New York

Ataxia with Oculomotor Apraxia Type 4 with PNKP Common “Portuguese” and Novel Mutations in Two Belarusian Families

Galina E. Rudenskaya
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Andrey V. Marakhonov
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Olga A. Shchagina
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Ekaterina R. Lozier
2  Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation
,
Elena L. Dadali
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Irina A. Akimova
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Nika V. Petrova
1  Department of Genetic Counseling, Research Centre for Medical Genetics, Moscow, Russian Federation
,
Fedor A. Konovalov
2  Independent Clinical Bioinformatics Laboratory, Moscow, Russian Federation
› Author Affiliations
Further Information

Publication History

25 December 2018

21 February 2019

Publication Date:
27 March 2019 (eFirst)

Abstract

Ataxia with oculomotor apraxia type 4 (AOA4) is a rare autosomal recessive, PNKP-related disorder delineated in 2015 in Portugal. We diagnosed AOA4 by next generation sequencing (NGS) followed by Sanger's sequencing in three boys from two unrelated Belarusian families. In both families, one of the heterozygous PNKP mutations was c.1123G>T, common in Portuguese patients; biallelic mutations, c.1270_1283dup14 and c.1029+2T>C, respectively, were novel. These are the first reported AOA4 Slavic cases and the first with a “Portuguese” PNKP mutation outside Portugal. Distinction in two brothers was microcephaly but their disease was not severe in contrast to PNKP-related “microcephaly, seizures, and developmental delay” and reported cases with features of both phenotypes.

Authors' Contribution

Authors G.E.R. and A.V.M. have designed the study; authors G.E.R., O.A.S., E.L.D., I.A.A., N.V.P. have collected data for the study; authors G.E.R., A.V.M., O.A.S., E.R.L., F.A.K. have done data analysis; and authors G.E.R., A.V.M. have prepared the manuscript.


Supplementary Material