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Novel Tecpr2 Variant in Two Cases of Hereditary Sensory and Autonomic Neuropathy Type 9: Insights From Genetic Characterization and Comprehensive Literature Review Publisher Pubmed



Moeinafshar A1, 2 ; Tehrani Fateh S1, 2 ; Hashemigorji F3 ; Karimzadeh P4 ; Gholibeglou E5 ; Rostami M1 ; Sadeghi H6 ; Miryounesi M1, 3, 6 ; Ghasemi MR1, 6
Authors
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Authors Affiliations
  1. 1. Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. School of Medicine, Tehran University of Medical Sciences (TUMS), Tehran, Iran
  3. 3. Genomic Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  4. 4. Pediatric Neurology Department, School of Medicine, Mofid Children’s Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Biology, Science and Research Branch, Islamic Azad University, Tehran, Iran
  6. 6. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: BMC Neurology Published:2024


Abstract

Background: Hereditary sensory and autonomic neuropathy type 9 (HSAN9) is a rare genetic disorder caused by genetic alterations in the TECPR2 locus and is characterized by developmental and intellectual disability, respiratory dysfunction, gastroesophageal reflux disease (GERD), and sensory and autonomic dysfunction, which are shared among the HSAN family. Methods: Whole-exome sequencing (WES) was performed on samples from both probands, and the relevant genetic variants were confirmed in their families using Sanger sequencing. Additionally, a comprehensive literature review was conducted on previously reported cases of HSAN9, and the clinical and genetic data were assessed to provide insight into the genetic and clinical characteristics of the disease. Results: We identified two new cases of HSAN9 with a shared novel variant of TECPR2 (NM_014844.5), c.1568del: p.Ser523PhefsTer12, classified as pathogenic according to ACMG guidelines. The probands showed characteristics of GERD, respiratory dysfunction, gait abnormalities, and developmental and speech delay, and both cases were deceased as a result of severe respiratory infection. The results of the literature review included 34 cases from 9 studies, revealing a wide range of genetic and clinical characteristics. Conclusions: Our study identified two new cases of HSAN9 with a novel variant in TECPR2, confirmed by WES. The clinical characteristics of the patients as well as the conduction of a comprehensive literature review are crucial in the early diagnosis and management of the disease and establishment of genotype-phenotype correlations. © The Author(s) 2024.
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