title: Identification of ATM mutations in Korean siblings with ataxia-telangiectasia.
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.
authors.affiliation: Department of Laboratory Medicine and Genetics, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea.
authors.forename: Hee Jae
authors.initials: HJ
authors.lastname: Huh
authors.forename: Kyoo-Ho
authors.initials: KH
authors.lastname: Cho
authors.forename: Ji Eun
authors.initials: JE
authors.lastname: Lee
authors.forename: Min-Jung
authors.initials: MJ
authors.lastname: Kwon
authors.forename: Chang-Seok
authors.initials: CS
authors.lastname: Ki
authors.forename: Phil Hyu
authors.initials: PH
authors.lastname: Lee
mesh_terms: D044466:Asian People / Q000235:genetics*; D001260:Ataxia Telangiectasia / Q000175:diagnosis / Q000235:genetics*; D064007:Ataxia Telangiectasia Mutated Proteins / Q000235:genetics*; D002648:Child; D005260:Female; D006579:Heterozygote; D006801:Humans; D007438:Introns; D008297:Male; D020125:Mutation, Missense; D010375:Pedigree; D056910:Republic of Korea; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017422:Sequence Analysis, DNA; D035781:Siblings
chemical_list: D064007:Ataxia Telangiectasia Mutated Proteins
keywords: Ataxia; Ataxia telangiectasia; Ataxia telangiectasia mutated protein; Korea