Trigenic ADH5/ALDH2/ADGRV1 mutations in myelodysplasia with Usher syndrome

• Published in: Heliyon 2021-08, Vol.7 (8), p.e07804-e07804, Article e07804
• Main Authors: Kinoshita, Shintaro, Ando, Miki, Ando, Jun, Ishii, Midori, Furukawa, Yoshiki, Tomita, Osamu, Azusawa, Yoko, Shirane, Shuichi, Kishita, Yoshihito, Yatsuka, Yukiko, Eguchi, Hidetaka, Okazaki, Yasushi, Komatsu, Norio
• Format: Article
• Language: English
• Subjects: ADH5/ALDH/ADGRV1 variants; Myelodysplastic syndrome; Trigenic mutations; Trio-next generation sequencing; Usher syndrome
• ISSN: 2405-8440; 2405-8440
• DOI: 10.1016/j.heliyon.2021.e07804

Trio-next generation sequencing is useful to identify undiagnosed inherited diseases. We have attended a patient with trigenic ADH5/ALDH2/ADGRV1 pathogenic variants, which caused two distinct diseases, myelodysplastic syndrome and Usher syndrome. Whole genome sequencing of peripheral blood from the patient and his parents were applied to identify disease-causing genes. Sanger sequencing was performed to validate the identified ADH5/ALDH2/ADGRV1 variants. Our results identified disease-associated variants in ADGRV1 (disease inheritance autosomal recessive) and in ADH5 (disease inheritance also autosomal recessive) and a variant in ALDH2 (disease inheritance autosomal dominant). Although the variants identified in ADH5 and ALDH2 have been reported, their co-existence in association with disease-causing variation in a third gene has not. They broaden the spectrum of ADGRV1 in Usher syndrome. Findings on next generation sequencing guided rapid and accurate diagnosis, resulting in patient-tailored therapeutic intervention. •Trigenic ADH5 / ALDH2 / ADGRV1 ​variants in myelodysplastic syndrome with Usher syndrome were identified.•Two novel pathogenic frameshift variants in ​ADGRV1 ​in compound heterozygous state with Usher syndrome type II were described.•Findings on next generation sequencing guided rapid and accurate diagnosis, resulting in patient-tailored therapy. ADH5/ALDH/ADGRV1 variants, Myelodysplastic syndrome, Trigenic mutations, Trio-next generation sequencing, Usher syndrome.