ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

Satoshi Katagiri; Yuya Negishi; Kei Mizobuchi; Mitsuyoshi Urashima; Tadashi Nakano; Takaaki Hayashi

doi:10.1155/2017/1079687

ABCC6 Gene Analysis in 20 Japanese Patients with Angioid Streaks Revealing Four Frequent and Two Novel Variants and Pseudodominant Inheritance

J Ophthalmol. 2017:2017:1079687. doi: 10.1155/2017/1079687. Epub 2017 Aug 20.

Authors

Satoshi Katagiri¹, Yuya Negishi^{1

2}, Kei Mizobuchi¹, Mitsuyoshi Urashima², Tadashi Nakano¹, Takaaki Hayashi^{1

3}

Affiliations

¹ Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
² Division of Molecular Epidemiology, The Jikei University School of Medicine, Tokyo, Japan.
³ Department of Ophthalmology, Katsushika Medical Center, The Jikei University School of Medicine, Tokyo, Japan.

Abstract

Purpose: To report the spectrum of ABCC6 variants in Japanese patients with angioid streaks (AS).

Patients and methods: This was a single-center cohort study. The medical records of 20 patients with AS from 18 unrelated Japanese families were retrospectively reviewed. Screening of the ABCC6 gene (exons 1 to 31) was performed using PCR-based Sanger sequencing.

Results: Eight ABCC6 variants were identified as candidate disease-causing variants. These eight variants included five known variants (p.Q378X, p.R419Q, p.V848CfsX83, p.R1114C, and p.R1357W), one previously reported variant (p.N428S) of unknown significance, and two novel variants (c.1939C>T [p.H647Y] and c.3374C>T [p.S1125F]); the three latter variants were determined to be variants of significance. The following four variants were frequently identified: p.V848CfsX83 (14/40 alleles, 35.0%), p.Q378X (7/40 alleles, 17.5%), p.R1357W (6/40 alleles, 15.0%), and p.R419Q (4/40 alleles, 10.0%). The ABCC6 variants were identified in compound heterozygous or homozygous states in 13 of 18 probands. Two families showed a pseudodominant inheritance pattern. Pseudoxanthoma elasticum was seen in 15 of 17 patients (88.2%) who underwent dermatological examination.

Conclusions: We identified disease-causing ABCC6 variants that were in homozygous or compound heterozygous states in 13 of 18 families (72.2%). Our results indicated that ABCC6 variants play a significant role in patients with AS in the Japanese population.