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- Title
A founder Alu insertion in RP1 gene in Japanese patients with retinitis pigmentosa.
- Authors
Nishiguchi, Koji Miura; Fujita, Kosuke; Ikeda, Yasuhiro; Kunikata, Hiroshi; Koyanagi, Yoshito; Akiyama, Masato; Abe, Toshiaki; Wada, Yuko; Sonoda, Koh-Hei; Nakazawa, Toru
- Abstract
Purpose: To screen for the 328 bp Alu insertion (c.4052_4053ins328, p.Tyr1352Alafs) in RP1 in a group of retinitis pigmentosa (RP) patients who had been previously identified with a heterozygous deleterious mutation in the gene. Study design: Prospective, clinical and experimental study. Methods: The Alu insertion in RP1 was screened with an optimized PCR-based method in 26 RP patients with a heterozygous deleterious mutation (nonsense or frameshift) in RP1 that had been identified in a preceding genetic study. The genetic location of the previously identified mutation and its inheritance pattern were assessed. Results: Out of 26 RP patients with a heterozygous deleterious mutation in RP1, 5 (19.2%) were found to carry an additional heterozygous Alu insertion, presumably resulting in a compound heterozygous state. This included 3 patients who had been previously diagnosed as autosomal dominant RP based on genetic findings. They were re-diagnosed as having an autosomal recessive disease following our new findings. In all patients identified with the Alu insertion, the other mutations found in the preceding study were outside the defined region in exon 4 (encoding amino acids 677 to 917) in which truncation mutations have been suggested to exert a dominant negative effect. Conclusion: The founder Alu insertion in RP1 is an important cause of autosomal recessive RP in Japanese patients and can be missed in standard targeted resequencing. Screening optimized for this mutation is warranted, particularly in patients with a heterozygous deleterious mutation outside the defined region in exon 4 of RP1.
- Subjects
RETINITIS pigmentosa; GENETIC mutation; AMINO acids; RECESSIVE genes; GENES
- Publication
Japanese Journal of Ophthalmology, 2020, Vol 64, Issue 4, p346
- ISSN
0021-5155
- Publication type
Article
- DOI
10.1007/s10384-020-00732-5