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19.03.2020 | Laboratory Investigation

A founder Alu insertion in RP1 gene in Japanese patients with retinitis pigmentosa

Zeitschrift:
Japanese Journal of Ophthalmology
Autoren:
Koji Miura Nishiguchi, Kosuke Fujita, Yasuhiro Ikeda, Hiroshi Kunikata, Yoshito Koyanagi, Masato Akiyama, Toshiaki Abe, Yuko Wada, Koh-Hei Sonoda, Toru Nakazawa
Wichtige Hinweise
Corresponding Author: Koji M Nishiguchi

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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.

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Literatur
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