Volume 13, Issue 1 (Feb 2025)
Res Mol Med (RMM) 2025, 13(1): 53-58 |
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Jalali H, Rajabi M, Rahimi M, Mahdavi M R. Identification of a Novel GNAI1 Variant (c.593T>A) Associated With Neurodevelopmental Disorder in an Iranian Family. Res Mol Med (RMM) 2025; 13 (1) :53-58
URL: http://rmm.mazums.ac.ir/article-1-602-en.html
URL: http://rmm.mazums.ac.ir/article-1-602-en.html
1- Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran.
2- Social Welfare Center, Mazandaran University of Medical Sciences, Sari, Iran.
3- Sinaye Mehr Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
4- Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. ,Mahdavi899@gmail.com
2- Social Welfare Center, Mazandaran University of Medical Sciences, Sari, Iran.
3- Sinaye Mehr Research Center, Mazandaran University of Medical Sciences, Sari, Iran.
4- Thalassemia Research Center, Hemoglobinopathy Institute, Mazandaran University of Medical Sciences, Sari, Iran. ,
Abstract: (823 Views)
Background: Neurodevelopmental disorders (NDDs) encompass a broad spectrum of conditions with diverse genetic and clinical presentations. Despite advances in sequencing technologies, many cases remain genetically unexplained, particularly those with variable phenotypes.
Materials and Methods: In this study, we report a novel heterozygous variant in the GNAI1 gene (c.593T>A; p.Met198Lys) in a 36-year-old man identified through whole-exome sequencing (WES). The presence of variant was also detected in three affected members of his family via sanger sequencing method using specific primers.
Results: Unlike previously reported GNAI1 mutations, which are typically de novo and associated with severe developmental delays, hypotonia, epilepsy, and dysmorphic features, the affected individuals in this family exhibited only mild intellectual disability. Sanger sequencing confirmed co-segregation of the variant with the disease phenotype, supporting an autosomal dominant inheritance pattern. In silico analyses classified the variant as likely pathogenic.
Conclusion: Given the clinical overlap between GNAI1-related NDDs and other single-gene disorders, such as GNB1, PPP3CA, and TANC2, this case highlights the importance of next-generation sequencing in uncovering elusive genetic etiologies and expands the phenotypic and inheritance spectrum of GNAI1-associated disorders.
Materials and Methods: In this study, we report a novel heterozygous variant in the GNAI1 gene (c.593T>A; p.Met198Lys) in a 36-year-old man identified through whole-exome sequencing (WES). The presence of variant was also detected in three affected members of his family via sanger sequencing method using specific primers.
Results: Unlike previously reported GNAI1 mutations, which are typically de novo and associated with severe developmental delays, hypotonia, epilepsy, and dysmorphic features, the affected individuals in this family exhibited only mild intellectual disability. Sanger sequencing confirmed co-segregation of the variant with the disease phenotype, supporting an autosomal dominant inheritance pattern. In silico analyses classified the variant as likely pathogenic.
Conclusion: Given the clinical overlap between GNAI1-related NDDs and other single-gene disorders, such as GNB1, PPP3CA, and TANC2, this case highlights the importance of next-generation sequencing in uncovering elusive genetic etiologies and expands the phenotypic and inheritance spectrum of GNAI1-associated disorders.
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