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Eur J Med Genet. 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.

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

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