Work

Concurrent inheritance of achromatopsia and MMAT syndrome in a pedigree: Genetic and clinical insights

Year: 2025

Type: article

Abstract: BACKGROUND: Achromatopsia is a rare type of retinal dystrophy presenting with decreased visual acuity, pendular nystagmus, photophobia, impaired color discrimination, and central scotoma. In this study, we investigated achromatopsia in a proband and his family. METHODS: Whole-exome sequencing identified two novel variants in PDE6H and ADAMTS18. The presence of the variants was confirmed by Sanger sequencing and it was further utilized to determine the zygosity status of other family members. Lastly, the clinical presentations of the patients were thoroughly assessed. RESULTS: We identified two novel variants in two genes among six patients from a pedigree: PDE6H (NM_006205.3):c.35C > G (p.SER12TER) and ADAMTS18 (NM_199355.4):c.3139C > T (p.ARG1047TER). The proband and two of his sisters were homozygous for the variant in PDE6H and heterozygous for the other one. The siblings complained of decreased visual acuity, impaired color discrimination, photophobia, and myopia. Ellipsoid zone disruption and pendular nystagmus were also noted in two and three of the patients, respectively. Two affected patients were heterozygous for the variant identified in PDE6H and homozygous for the variant detected in ADAMTS18. These two are the second generation of the family, born to non-consanguineous parents. Both presented with microcornea, myopia, and telecanthus. Punctual atresia and strabismus were also noted. CONCLUSION: Pathogenic variants in PDE6H and ADAMTS18 can cause a broad range of ophthalmic disorders. We suggest that the study of rare congenital genetic diseases in developing countries should be prioritized due to the differences in their environments and the issues care givers are confronted with when trying to face them.

Source: European Journal of Medical Genetics

DOI: 10.1016/j.ejmg.2025.105045