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ALDH1A3-related congenital microphthalmia-8 due to a novel frameshift variant
Fahimeh Piryaei1, Rezvan Pakmanesh2, Maryam Salehirad2
1Department of Molecular Medicine and Genetics, School of Medicine, Hamadan University of Medical Sciences, Hamadan, Iran.
Abstract:
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.
Insights
Microphthalmia-8, a severe eye malformation, is linked to ALDH1A3 gene mutations. This study identifies a novel ALDH1A3 variant in a child with congenital microphthalmia, emphasizing the need for genetic counseling.
Area of Science:
- Genetics
- Ophthalmology
- Developmental Biology
Background:
- Microphthalmia (MCOP) is a rare congenital eye malformation affecting approximately 1 in 7000 live births, leading to blindness.
- Isolated microphthalmia-8 (MCOP8) is an autosomal recessive condition linked to mutations in the ALDH1A3 gene.
Observation:
- A case report of an 8-year-old boy with severe bilateral microphthalmia, a left eye cyst, and blindness since birth.
- The patient, from a consanguineous family with no prior history of the condition, also developed behavioral disorders at age 7.
Findings:
- Whole Exome Sequencing (WES) identified a novel pathogenic variant, c.1441delA (p.M482Cfs*8), in the ALDH1A3 gene in the proband.
- Sanger sequencing confirmed the presence of this variant, establishing a genetic link to the patient's severe microphthalmia.
Implications:
- This finding expands the mutational spectrum of the ALDH1A3 gene in MCOP8.
- Prenatal diagnosis is recommended for this family in future pregnancies to detect MCOP8 early.
- Understanding the genetic basis of MCOP is crucial for diagnosis, counseling, and potential therapeutic strategies.
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