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The First Iranian Patient With You-Hoover-Fong Syndrome and a Review of the Literature on 27 Cases: Expanding the Genotypic and Phenotypic Spectrum Publisher



Shokrollahi N1 ; Tehrani Fateh S2 ; Nouri M1 ; Behnam A1 ; Moghimi P3, 4 ; Sadeghi H5 ; Mirfakhraie R5 ; Roudgari H4 ; Jamshidi S4 ; Miryounesi M4, 5 ; Ghasemi MR4, 5
Authors
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Authors Affiliations
  1. 1. School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  2. 2. School of Medicine, Tehran University of Medical Sciences, Tehran, Iran
  3. 3. School of Medicine, Islamic Azad University Tehran Medical Sciences, Tehran, Iran
  4. 4. Center for Comprehensive Genetic Services, Shahid Beheshti University of Medical Sciences, Tehran, Iran
  5. 5. Department of Medical Genetics, Faculty of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

Source: Neurological Sciences Published:2024


Abstract

Background: The ultra-rare autosomal recessive genetic disorder, You-Hoover-Fong Syndrome (YHFS), is caused by defects in the TELO2 gene and is characterized by intellectual disability, developmental delay, and ocular impairments. This study aims to contribute to a better understanding of YHFS by reviewing previous cases and introducing a novel variant in a new case. Methods: Whole exome sequencing (WES) was conducted on the proband to identify genetic variants, and Sanger sequencing was used to confirm variants within the family. This article presents a comprehensive collection of reported cases of YHFS, incorporating both molecular and clinical data, through an extensive literature search and analysis of English-language studies published until June 2023. Results: Using WES, a novel homozygous missense variant, c.1799A > G (p. Tyr600Cys), was identified in the TELO2 gene in a 4-year-old Iranian male patient. Novel clinical features, including choanal atresia and clubfoot, were also identified. A comprehensive literature review identified 27 patients with YHFS, with 20 variants in the TELO2 gene. Missense pathogenic variants were the most common type of pathogenic variant, and the most common features were microcephaly and intellectual impairment. Conclusion: This study presents the first case of pathogenic variants in TELO2 gene in Iran, expands the genotypic and phenotypic spectrum of YHFS and contributes to the growing body of literature pertaining to YHFS. Furthermore, our findings highlight the importance of genetic testing for non-consanguineous carrier screening, as compound heterozygosity may be a significant factor in the development of YHFS. Further research is needed to clarify the molecular mechanisms underlying YHFS pathogenesis. Graphical Abstract: (Figure presented.). © Fondazione Societa Italiana di Neurologia 2024.
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