ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant

• DOI: 10.1016/j.ejmg.2023.104801
• Publication Date: 2023-06-18T05:25:19Z
• Authors: Fahimeh Piryaei; Rezvan Pakmanesh; Maryam Salehirad; Soheila Akbari; Masoud Edizadeh; Hamidreza Khodadadi
• Keywords: Male; Mutation; Humans; Anophthalmos; Microphthalmos; Child; Blindness; Aldehyde Oxidoreductases; 3. Good health; Pedigree

Microphthalmia (MCOP) is a group of rare developmental malformations of eye with often reduced size of the eyeball, leading to blindness. Affecting about 1 in 7000 live births, MCOP can occur due to either environmental or genetic factors. Isolated microphthalmia-8 (MCOP8) has been proved to be caused by autosomal recessive mutations of the ALDH1A3 gene (MIM*600463) encoding aldehyde dehydrogenase 1 family, member A3. Herein, we report an 8-year-old boy with vision problems since birth from a first-cousin consanguineous parents. The main symptoms of the patient included severe bilateral microphthalmia, cyst in the left eye and blindness. The child developed behavioral disorders at the age of 7. It should be noted that there is no family history of the disease. To identify the genetic factor underlying the pathogenesis in this case Whole Exome Sequencing (WES) was performed and followed by Sanger sequencing. A novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene was detected by WES in the proband. Further prenatal diagnosis is highly suggested to the family for the future pregnancies.