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Bi-Allelic Loss of Function Variant in the Nrcam Gene Is Associated With Motor-Predominant Axonal Polyneuropathy; the Second Report Publisher Pubmed



Elahi Z1, 2 ; Soveyzi M1 ; Nafissi S3, 4 ; Nilipour Y5 ; Goleyjanimoghadam M1 ; Keshavarz E6 ; Kariminejad A2 ; Najmabadi H1, 2 ; Fattahi Z1, 2
Authors
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Authors Affiliations
  1. 1. Genetics Research Center, University of Social Welfare and Rehabilitation Sciences, Tehran, Iran
  2. 2. Kariminejad-Najmabadi Pathology & Genetics Center, Tehran, Iran
  3. 3. Neuromuscular Research Center, Tehran University of Medical Sciences, Tehran, Iran
  4. 4. Department of Neurology, Shariati Hospital, Tehran University of Medical Sciences, Tehran, Iran
  5. 5. Pediatric Pathology Research Center, Research Institute for Children's Health, Mofid Children Hospital, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  6. 6. Department of Radiology, Mahdiyeh Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Molecular Genetics and Genomic Medicine Published:2023


Abstract

Background: The role of biallelic variants in the NRCAM gene underlying a neurodevelopmental disorder has been defined recently. The phenotype is mainly recognized by varying severity of global developmental delay/intellectual disability, hypotonia, spasticity, and peripheral neuropathy. Methods: Here, we describe a patient with an initial diagnosis of motor-predominant axonal polyneuropathy or a form of distal SMA. Whole-exome sequencing (WES), in parallel with WES-based CNV detection and assessment of homozygosity runs, was performed to identify this patient's possible genetic cause. Results: Whole exome sequencing revealed a homozygous variant, c.73C > T (p.Gln25*), in the NRCAM gene, while the patient manifests a mild range of phenotypes compared to NRCAM-related disorder. He presented only motor-predominant axonal polyneuropathy with no other signs of central nervous system involvement. Conclusions: This study is the second report of an association between biallelic NRCAM gene variants and a Mendelian disorder. The obtained clinical data, together with the molecular findings in this patient, expands the clinical and molecular spectrum of NRCAM-related disorder and highlights its phenotypic complexity. Although patients with loss of function variants in this gene have previously presented severe clinical features, we show that type of the pathogenic variant does not necessarily determine the severity of this phenotype. © 2023 The Authors. Molecular Genetics & Genomic Medicine published by Wiley Periodicals LLC.
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