https://www.ncbi.nlm.nih.gov/pubmed/30772474

2019 Feb 14. pii: S1769-7212(18)30902-9. doi: 10.1016/j.ejmg.2019.02.003. [Epub ahead of print]

ATM mutation spectrum in Russian children with ataxia-telangiectasia.

Suspitsin E¹, Sokolenko A², Bizin I³, Tumakova A⁴, Guseva M⁴, Sokolova N⁵, Vakhlyarskaya S⁶, Kondratenko I⁶, Imyanitov E⁷.

Author information

1: St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia. Electronic address: evgeny.suspitsin@gmail.com.
2: St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.
3: N.N. Petrov Institute of Oncology, St.-Petersburg, Russia.
4: St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia.
5: First City Children Hospital, St.-Petersburg, Russia.
6: Russian Children Clinical Hospital, N.N. Pirogov National Research Medical University, Moscow, Russia.
7: St.-Petersburg Pediatric Medical University, St.-Petersburg, Russia; N.N. Petrov Institute of Oncology, St.-Petersburg, Russia; I.I. Mechnikov North-Western Medical University, St.-Petersburg, Russia; St.-Petersburg State University, St.-Petersburg, Russia.

Abstract

Ataxia-telangiectasia (AT) is a severe autosomal recessive orphan disease characterized by a number of peculiar clinical manifestations. Genetic diagnosis of AT is complicated due to a large size of the causative gene, ATM. We used next-generation sequencing (NGS) technology for the ATM analysis in 17 children with the clinical diagnosis of AT. Biallelic mutations in the ATM gene were identified in all studied subjects; these lesions included one large gene rearrangement, which was reliably detected by NGS and validated by multiplex ligation-dependent probe amplification (MLPA). There was a pronounced founder effect, as 17 of 30 (57%) pathogenic ATM alleles in the patients of Slavic origin were represented by three recurrent mutations (c.5932G > T, c.450_453delTTCT, and c.1564_1565delGA). These data have to be taken into account while considering the genetic diagnosis and screening for ataxia-telangiectasia syndrome.

KEYWORDS:

Ataxia-telangiectasia; Founder effect; Mutation

PMID:: 30772474
DOI:: 10.1016/j.ejmg.2019.02.003