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The first Japanese family of CDH3-related hypotrichosis with juvenile macular dystrophy
Takaaki Hayashi1,2, Satoshi Katagiri1, Daiki Kubota3
1Department of Ophthalmology, The Jikei University School of Medicine, Tokyo, Japan.
Insights
Two Japanese siblings with Hypotrichosis with juvenile macular dystrophy (HJMD) were identified with novel CDH3 gene variants. This rare disorder causes progressive vision loss and hair thinning.
Area of Science:
- Genetics
- Ophthalmology
- Dermatology
Background:
- Hypotrichosis with juvenile macular dystrophy (HJMD) is a rare, autosomal recessive inherited disorder.
- It is caused by biallelic variants in the CDH3 gene, which encodes P-cadherin.
Observation:
- Two Japanese siblings presented with HJMD, exhibiting progressive vision loss and macular atrophy.
- Ophthalmic examinations revealed chorioretinal atrophy, while dermatological exams showed sparse, fragile scalp hair.
Findings:
- Whole-exome sequencing identified novel compound heterozygous CDH3 variants [c.123_129dupAGGCGCG (p.Glu44fsX26) and c.2280+1G>T] in both patients.
- Electroretinography confirmed severely reduced macular function correlating with atrophy, despite near-normal generalized retinal function.
Implications:
- This study reports the first Japanese patients with HJMD and novel CDH3 variants.
- The findings expand the understanding of CDH3-related HJMD, aiding ophthalmologists and dermatologists in diagnosis and management.
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.
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