Molecular and clinical characterization of Thai patients with achromatopsia: identification of three novel disease-assoc
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ORIGINAL PAPER
Molecular and clinical characterization of Thai patients with achromatopsia: identification of three novel diseaseassociated variants in the CNGA3 and CNGB3 genes Worapoj Jinda . Aekkachai Tuekprakhon . Wanna Thongnoppakhun . Chanin Limwongse . Adisak Trinavarat . La-ongsri Atchaneeyasakul
Received: 1 May 2020 / Accepted: 17 August 2020 Ó Springer Nature B.V. 2020
Abstract Purpose Achromatopsia (ACHM) is an autosomal recessive cone disorder characterized by pendular nystagmus, photophobia, reduced visual acuity, and partial or total absence of color vision. Mutations in six genes (CNGA3, CNGB3, GNAT2, PDE6C, PDE6H, and ATF6) have been reported in ACHM. There is no information on these disease-associated genes in Thai population. This study aimed to investigate the molecular and clinical characteristics in Thai patients with ACHM. Methods Seven unrelated Thai patients with ACHM were recruited. Detailed ophthalmologic examination was performed. Polymerase chain reaction (PCR)Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10792-020-01559-2) contains supplementary material, which is available to authorized users. W. Jinda W. Thongnoppakhun C. Limwongse Division of Medical Genetics Research and Laboratory, Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
coupled single-strand conformation polymorphism (SSCP) screening followed by Sanger sequencing was used to identify sequence variants in all exons and splice junctions of three genes (CNGA3, CNGB3, and GNAT2). The pathogenicity of the detected variants was interpreted. Segregation analysis was performed to determine variant sharing in available family members. Results Four patients displayed different SSCP migration patterns. Sequence analysis revealed a reported pathogenic and a novel disease-associated variant in the CNGA3 gene. For the CNGB3 gene, we found two novel disease-associated variants and a reported variant of uncertain significance (VUS). Segregation analysis confirmed that the variants identified in each patient were present in the heterozygous state in their corresponding family members,
A. Trinavarat L. Atchaneeyasakul (&) Department of Ophthalmology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand e-mail: [email protected]
A. Tuekprakhon Clinical Molecular Pathology Laboratory, Department of Clinical Pathology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand C. Limwongse Division of Medical Genetics, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
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which was consistent with an autosomal recessive mode of inheritance. Conclusions This study demonstrated the first molecular and clinical characterization of ACHM in Thai patients. The identification of disease-associated genes in a specific population leads to a personalized gene therapy benefiting those
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