Trigenic ADH5/ALDH2/ADGRV1 mutations in myelodysplasia with Usher syndrome.
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.
['Kinoshita|Shintaro|S|', 'Ando|Miki|M|', 'Ando|Jun|J|', 'Ishii|Midori|M|', 'Furukawa|Yoshiki|Y|', 'Tomita|Osamu|O|', 'Azusawa|Yoko|Y|', 'Shirane|Shuichi|S|', 'Kishita|Yoshihito|Y|', 'Yatsuka|Yukiko|Y|', 'Eguchi|Hidetaka|H|', 'Okazaki|Yasushi|Y|', 'Komatsu|Norio|N|']
Usher syndrome Trio-next generation sequencing Myelodysplastic syndrome ADH5/ALDH/ADGRV1 variants Trigenic mutations