Trigenic ADH5/ALDH2/ADGRV1 mutations in myelodysplasia with Usher syndrome. Issue 8 (August 2021)

• Record Type: Journal Article
• 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
• Is Part Of: Heliyon. Volume 7:Issue 8(2021)
• Publication Date: 2021-08
• Subjects: ADH5/ALDH/ADGRV1 variants -- Myelodysplastic syndrome -- Trigenic mutations -- Trio-next generation sequencing -- Usher syndrome; Research -- Periodicals; Medical sciences -- Periodicals; Natural history -- Periodicals; Social sciences -- Periodicals; Earth sciences -- Periodicals; Physical sciences -- Periodicals; 507.2
• DOI: 10.1016/j.heliyon.2021.e07804
• Languages: English
• ISSNs: 2405-8440

Abstract

Abstract: 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. Highlights: 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. Abstract : ADH5/ALDH/ADGRV1 variants, Myelodysplastic syndrome, Trigenic mutations, Trio-next generation sequencing, Usher syndrome.