The first Japanese family of CDH3‐related hypotrichosis with juvenile macular dystrophy

Molecular Genetics & Genomic Medicine

Akihiko Asahina¹  Yozo Ishiuji¹  Shuhei Kameya²  Daiki Kubota²  Takaaki Hayashi³  Tadashi Nakano³  Kei Mizobuchi³  Satoshi Katagiri³ 

[1] Department of Dermatology The Jikei University School of Medicine Tokyo Japan;Department of Ophthalmology Nippon Medical School Chiba Hokusoh Hospital Chiba Japan;Department of Ophthalmology The Jikei University School of Medicine Tokyo Japan;

关键词: CDH3;    electroretinography;    hypotrichosis;    Japanese;    macular dystrophy;    retina;   

DOI  :  10.1002/mgg3.1688

来源: DOAJ

【 摘 要 】

Abstract Background Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare autosomal recessive inherited disorder caused by biallelic variants in the CDH3 gene encoding P‐cadherin. Here, we report two Japanese sibling patients with HJMD. Methods Whole‐exome sequencing (WES) was performed to identify disease‐causing variants. In addition, ophthalmic and dermatological examinations were performed to classify the phenotype of each patient. Results The WES analysis revealed novel compound heterozygous CDH3 variants [c.123_129dupAGGCGCG (p.Glu44fsX26) and c.2280+1G>T] in both patients; the unaffected, nonconsanguineous parents each exhibited one of the variants. Both patients showed the same clinical findings. Ophthalmologically, they exhibited progressive loss of visual acuity and chorioretinal macular atrophy, as examined with fundoscopy, fundus autofluorescence imaging, and optical coherence tomography. Full‐field electroretinography, assessing generalized retinal function, revealed nearly normal amplitudes of both rod‐ and cone‐mediated responses. Multifocal electroretinography, reflecting macular function, showed extremely decreased responses in the central area, corresponding to the chorioretinal atrophy. Dermatological examination revealed diffuse thinning of the scalp hair, which was sparse and fragile. Conclusion This is the first report of Japanese patients with HJMD and novel compound heterozygous truncating variants in CDH3. Our findings can expand the knowledge and understanding of CDH3‐related HJMD, which could be helpful to ophthalmologists and dermatologists.

【 授权许可】

Unknown