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A Novel Homozygote Pathogenic Variant in the Diaph1 Gene Associated With Seizures, Cortical Blindness, and Microcephaly Syndrome (Scbms): Report of a Family and Literature Review Publisher Pubmed



Esmaeilzadeh E1 ; Biglari S2, 3, 4 ; Mosallaei M1 ; Khorshid HRK5 ; Vahidnezhad H3, 4, 6 ; Tabatabaiefar MA2
Authors
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Authors Affiliations
  1. 1. Fetal Health Research Center, Hope Generation Foundation, Tehran, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Center for Applied Genomics, Children's Hospital of Philadelphia, Philadelphia, PA, United States
  4. 4. Department of Pediatrics, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, United States
  5. 5. Genetics Research Center, University of Social Welfare and Rehabilitation Science, Tehran, Iran
  6. 6. Division of Human Genetics, Children's Hospital of Philadelphia, Philadelphia, PA, United States

Source: Molecular Genetics and Genomic Medicine Published:2024


Abstract

Objective: Mammalian Diaphanous-Related Formin (mDia1), which is encoded by the DIAPH1 gene, serves as essential for the regulation of cell morphology and cytoskeletal organization. The role of DIAPH1 in brain development has been extensively established. This study aims to evaluate the clinical, neuroradiological, and genetic characteristics of patients with DIAPH1-related disease and determine probable genotype–phenotype relationships. Methods: In the current study, exome sequencing was performed to identify the genetic basis of the clinical presentation in an Iranian 7-year-old boy. Validation of the detected variant was done by Sanger sequencing. Furthermore, we performed a comprehensive review of the literature. Results: Here, we detected a novel homozygous c.1285C> T (p.Gln429*) pathogenic variant in the patient. In silico analysis with prediction software tools identified this variant as a probable source of damage. Twenty cases from seven studies were found after a review of the literature. The patients' main symptoms were a developmental delay, microcephaly, and seizures. The mean age of onset for patients in the group of 20 patients with a known age of onset was 2.3 months (SD = 1.6). Of the variants identified, c.2769del, c.684+1G>A, and c.2332C> T were identified in 72% of the patients. Conclusion: Considering the variant's position in the gene and the encoding protein, a pathogenic effect is predicted for the variant. So, the patient's clinical manifestation is probably caused by this pathogenic variant. Moreover, by studying clinical manifestations in all molecularly confirmed reported cases, provided a comprehensive overview of clinical presentation, and attempted to find a genotype–phenotype correlation. © 2024 The Author(s). Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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