Clinical Association of Ataxia Telangiectasia-Like Disorder 1 with an Uncertain Significance Variant in the MRE11 Gene: A Case Report

Barazandeh Shirvan, Bita; Akhondian, Javad; Layegh, Parvaneh; Hashemi, Narges; Ghayoor Karimiani, Ehsan; Rezaie, Razie; Najarzadeh Torbati, Paria; Beiraghi Toosi, Mehran

doi:10.22038/rcm.2024.81480.1500

Clinical Association of Ataxia Telangiectasia-Like Disorder 1 with an Uncertain Significance Variant in the MRE11 Gene: A Case Report

Document Type : Case report

Authors

Bita Barazandeh Shirvan ¹

Javad Akhondian ²

Parvaneh Layegh ³

Narges Hashemi ⁴

Ehsan Ghayoor Karimiani ⁵

Razie Rezaie ⁶

Paria Najarzadeh Torbati ⁷

mehran beiraghi toosi ⁸

¹ Neuroscience Research Center, Mashhad University of Medical Sciences, Mashhad, Iran.

² Department of pediatric neurology, Ghaem hospital, Mashhad University of Medical Sciences, Mashhad, Iran

³ Department of Radiology, Faculty of Medicine, Mashhad University of Medical Sciences, Mashhad, Iran.

⁴ Department of Pediatrics, School of Medicine, Mashhad University of Medical Sciences, ‎Mashhad, Iran

⁵ Next Generation Genetic Polyclinic, Mashhad, Iran. Honorary Researcher, University of Manchester, UK

⁶ Neuroscience Research Centre, Mashhad University of Medical Sciences, Mashhad, Iran Blood Transfusion Organization, Mashhad, Iran

⁷ paria22njz@gmail.com

⁸ Pediatric ward of mashhad university of medical sciences

10.22038/rcm.2024.81480.1500

Abstract

Objective: Ataxia telangiectasia-like disorder (ATLD) is a rare autosomal recessive disorder caused by mutations in the MRE11 gene. The diagnosis of patients with Ataxia telangiectasia-like disorder and Ataxia telangiectasia may be challenging due to similar clinical manifestations. In the present study, we describe a patient with a homozygous variant of uncertain significance (VUS) in the MRE11 gene that was correlated clinically with ATLD.
Methods: We performed a brain MRI scan to find the cause of the patient's ataxia. After ventriculoperitoneal shunting due to obstructive hydrocephalus, there was no clinical change; so, we carried out whole exome sequencing. Additionally, Variants were classified using several databases and predicted according to the ACMG 2015 guidelines.
Results: A 2-year-6-month-old boy with ataxia, tonic seizure, and speech delay was found during studies. The WES and in silico analysis identified a homozygous variant of uncertain significance (VUS) in the MRE11 NM_005591.4 (MRE 11): c.173 G>T (p. GIv58Val).
Conclusion: This case report highlights that genetic testing can be useful for the precise diagnosis when clinical manifestations are not associated with MRI results. Furthermore, we could categorize a variant in the MRE11 gene from VUS to likely pathogenic based on clinical features.

Keywords

Keywords: Ataxia Telangiectasia-Like Disorder

MRE11

VUS

WES