Ann Lab Med.  2013 May;33(3):217-220. 10.3343/alm.2013.33.3.217.

Identification of ATM Mutations in Korean Siblings with Ataxia-Telangiectasia

• Huh HJ
• Cho KH
• Lee JE
• Kwon MJ
• Ki CS
• Lee PH

• KMID: 1781331
• DOI: http://doi.org/10.3343/alm.2013.33.3.217

Abstract

Ataxia-telangiectasia (A-T) is a rare autosomal recessive neurodegenerative disorder. It is characterized by early-onset, progressive cerebellar ataxia, oculomotor apraxia, choreoathetosis, conjunctival telangiectasias, immunodeficiency, and an increased risk of malignancy. Although A-T is known to be the most common cause of progressive cerebellar ataxia in childhood, there have been no confirmed cases in Korea. We report the clinical and genetic findings of Korean siblings who presented with limb and truncal ataxia, oculomotor apraxia, choreoathetosis, and telangiectasias of the eyes. Sequence analysis of the ataxia-telangiectasia mutated (ATM) gene revealed a known missense mutation (c.8546G>C; p.Arg2849Pro) and a novel intronic variant of intron 17 (c.2639-19_2639-7del13). Reverse-transcription PCR and sequencing analysis revealed that the c.2639-19_2639-7del13 variant causes a splicing aberration that potentiates skipping exon 18. Because A-T is quite rare in Korea, the diagnosis of A-T in Korean patients can be delayed. We recommend that a diagnosis of A-T should be suspected in Korean patients exhibiting the clinical features of A-T.

Keyword

Ataxia; Ataxia telangiectasia; Ataxia telangiectasia mutated protein; Korea

MeSH Terms

Asian Continental Ancestry Group/*genetics
Ataxia Telangiectasia/diagnosis/*genetics
Ataxia Telangiectasia Mutated Proteins/*genetics
Child
Female
Heterozygote
Humans
Introns
Male
Mutation, Missense
Pedigree
Republic of Korea
Reverse Transcriptase Polymerase Chain Reaction
Sequence Analysis, DNA
Siblings
Ataxia Telangiectasia Mutated Proteins

Figure

• 

  Fig. 1 (A) Pedigree of the family with A-T and (B-C) genomic DNA sequence analysis of the ATM gene in the proband and his siblings. (B) The patient was identified as being compound heterozygous for mutations of the ATM gene. The solid arrow indicates overlapping peaks at nucleotide position 8,546 because of a heterozygous G>C transition (c.8546G>C, p.Arg2849Pro). (C) The open arrow indicates the presence of successive double peaks at nucleotide position 2,639-19, suggesting the deletion of 13 base pairs (c.2639-19_2639-7delGAGTGCTTTTTAT).Abbreviations: A-T, ataxia-telangiectasia; ATM, ataxia-telangiectasia mutated.

• 

  Fig. 2 RT-PCR sequencing of the ATM gene. (A) Electrophoresis of RT-PCR products using the primer pair described in the Case Report demonstrates an additional band (954 bp), as well as the expected band (1,154 bp), in the proband. The density of the aberrant band is much stronger in the proband than in controls. (B) Sequencing of the RT-PCR products demonstrated the aberrant skipping of exon 18.Abbreviations: RT-PCR, reverse-transcription polymerase chain reaction; ATM, ataxia-telangiectasia mutated.

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