講演情報
[O23-5]複合ヘテロ接合性ABCA2バリアントによる知的障害を呈する症例
○井上 優太1, 土田 奈緒美1,2, Ae Kim Chong3, de Oliveira Stephen Bruno3, Augusto Araujo Castro Matheus3, Sayuri Honjo Rachel3, Romeo Bertola Debora3, 内山 由理1,2, 濱中 耕平1, 藤田 京志1, 輿水 江里子1, 三澤 計治1, 宮武 聡子1,4, 水口 剛1, 松本 直通1 (1.横浜市立大学 医学研究科 遺伝学, 2.横浜市立大学附属病院 難病ゲノム診断科, 3.Clinical Genetics Unit, Instituto da Crianca, Hospital das Clinicas HCFMUSP, Faculdade de Medicina, Universidade de Sao Paulo, Sao Paulo, Brazil, 4.横浜市立大学附属病院 遺伝子診療科)
ABCA2 at 9q34.3 encodes ATP Binding Cassette Subfamily A Member 2. ABCA2 variants lead to intellectual developmental disorder with poor growth and with or without seizures or ataxia (IDPOGSA, MIM#618808) in an autosomal recessive fashion. Recently, five homozygous ABCA2 truncating variants have been reported in 8 patients from 5 families. Most reported patients showed intellectual disability and developmental delay. Some patients had ataxia and dysarthria. In this study, we identified novel compound heterozygous ABCA2 variants by whole-exome sequencing in a 24-year-old Korean female patient with intellectual disability and hypernasal speech. These variants included a maternally inherited nonsense variant and a paternally inherited intronic variant. The intronic variant is a rare variant registered in gnomAD with an allele frequency of 0.005359%. Two in-silico tools (SpliceAI and SpliceRover) predict splicing alteration. RT-PCR using lymphoblastoid cells derived from the patient showed two aberrant transcripts (frameshift variant of 68 bp deletion and in-frame 5 amino acids insertion). These aberrant transcripts were confirmed to be subjected to nonsense-mediated mRNA decay. We also evaluated the clinical features of our case. Phenotype-genotype correlation of ABCA2-related syndrome will be discussed.