CDHR1 mutations in retinal dystrophies.

Area of Science:

• Ophthalmology
• Genetics
• Molecular Biology

Background:

• Inherited retinal dystrophies, including retinitis pigmentosa (RP), cone-rod dystrophy (CRD), and cone dystrophy (CD), significantly impact vision.
• The CDHR1 gene has been implicated in rare cases of these conditions, but its full mutational spectrum and associated clinical presentations remain incompletely understood.

Purpose of the Study:

• To investigate the role of the CDHR1 gene in patients presenting with autosomal recessive RP, CRD, or CD.
• To identify and characterize novel pathogenic variants within the CDHR1 gene and correlate them with clinical findings.

Main Methods:

• Ophthalmic examinations were conducted on 13 subjects (7 sporadic, 6 familial).
• Next-generation sequencing targeted 105 genes for mutation screening; homozygosity mapping and candidate gene analysis were used in one family.
• Bioinformatic analyses and minigene assays were employed to assess variant pathogenicity.

Main Results:

• Eleven distinct, novel CDHR1 variants were identified in nine index cases, all consistent with autosomal recessive inheritance.
• In silico predictions and minigene assays confirmed the pathogenic potential of identified variants, including two non-canonical splice site mutations causing missplicing.
• The study expands the known spectrum of CDHR1 mutations and associated retinal dystrophy phenotypes.

Conclusions:

• Mutations in the CDHR1 gene represent a rare but significant cause of inherited retinal dystrophies.
• This research broadens the understanding of CDHR1's contribution to visual impairment and highlights the importance of genetic analysis in diagnosing these conditions.