Abstract
The gene for ATP binding cassette subfamily A member 2 (ABCA2) is located at chromosome 9q34.3. Biallelic ABCA2 variants lead to intellectual developmental disorder with poor growth and with or without seizures or ataxia (IDPOGSA). In this study, we identified novel compound heterozygous ABCA2 variants (NM_001606.5:c.[5300–17C>A];[6379C>T]) by whole exome sequencing in a 28-year-old Korean female patient with intellectual disability. These variants included intronic and nonsense variants of paternal and maternal origin, respectively, and are absent from gnomAD. SpliceAI predicted that the intron variant creates a cryptic acceptor site. Reverse transcription-PCR using RNA extracted from a lymphoblastoid cell line of the patient confirmed two aberrant transcripts. Her clinical features are compatible with those of IDPOGSA.
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Data availability
The data of this study are not publicly available due to concerns regarding patient anonymity. Requests to access the data should be directed to the corresponding author. Only anonymized data are available to researchers upon request.
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Acknowledgements
We would like to thank the patient and her family for their participation in this study. We are also grateful to Ms. Sayaka Sugimoto, Ms. Mai Sato, Ms. Nobuko Watanabe, Ms. Kaori Takabe, and Mr. Takafumi Miyama at the Department of Human Genetics, Yokohama City University Graduate School of Medicine for their excellent technical assistance. We thank Rachel James, PhD, from Edanz (https://jp.edanz.com/ac) for editing a draft of this manuscript.
Funding
This work was supported by the Japan Agency for Medical Research and Development (AMED) (grant numbers JP23ek0109674, JP23ek0109549, JP23ek0109617, JP23ek0109648 to N. Matsumoto); the Japan Society for the Promotion of Science (JSPS) KAKENHI Grant-in-Aid for Scientific Research (grant numbers JP20K17936 and JP22K15901 to A. Fujita, JP23H02829 to S. Miyatake, JP23H02877 to T. Mizuguchi, JP22K15901 to K. Hamanaka, JP23K07229 to Y. Uchiyama, JP23K15353 to N. Tsuchida, and JP21K07869 to E. Koshimizu); the Takeda Science Foundation (T. Mizuguchi and N. Matsumoto); and Kawano Masanori Memorial Public Interest Incorporated Foundation for Promotion of Pediatrics (S. Miyatake).
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Inoue, Y., Tsuchida, N., Kim, C.A. et al. Novel compound heterozygous ABCA2 variants cause IDPOGSA, a variable phenotypic syndrome with intellectual disability. J Hum Genet 69, 163–167 (2024). https://doi.org/10.1038/s10038-024-01219-8
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DOI: https://doi.org/10.1038/s10038-024-01219-8
