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Griscelli Syndrome Type 1: A Novel Pathogenic Variant, and Review of Literature Publisher Pubmed



Khorram E1 ; Tabatabaiefar MA1 ; Yaghini O2 ; Khorrami M1 ; Yazdani V3 ; Fakhr F1 ; Amini M4 ; Kheirollahi M1
Authors
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Authors Affiliations
  1. 1. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Pediatrics, School of Medicine, Growth and Development Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Department of Biology, Islamic Azad University, East Tehran Branch, Tehran, Iran
  4. 4. Department of Medical Genetics, School of Medicine, Tehran University of Medical Sciences, Tehran, Iran

Source: Molecular Genetics and Genomics Published:2023


Abstract

Griscelli syndrome type 1 (GS1) is a rare inherited autosomal recessive disease caused by a deleterious variant in the MYO5A gene and characterized by general hypopigmentation, neurological symptoms, motor disability, hypotonia, and vision abnormality. Only nine pathogenic variants in the MYO5A gene have been confirmed in association with the GS1. All of the reported pathogenic variants are truncating. Herein, two siblings from a consanguineous Iranian family with abnormal pigmentation and neurological symptoms were referred for genetic counseling. Whole-exome sequencing (WES) revealed a novel homozygous truncating variant c.1633_1634delAA (p.Asn545Glnfs*10) in the MYO5A gene, which was completely co-segregated with the phenotype in all affected and unaffected family members. Computational analysis and protein modeling demonstrated the deleterious effects of this variant on the structure and function of the protein. The variant, according to ACMG guidelines, was classified as pathogenic. Besides the novelty of the identified variant, our patients manifested more severe clinical symptoms and presented distal hyperlaxity in all four limbs, which was a new finding. In conclusion, we expanded the mutational and phenotypic spectrum of the GS1. 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. © 2023, The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.
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