Abstract

Germline ATM gene variations result in phenotypic heterogeneity characterized by a variable degree of disease severity. We retrospectively collected clinical, genetic, and immunological data of 26 cases with A-T. Clinical manifestations included oculocutaneous telangiectasia (100%), ataxia (100%), fever, loose stools or infection (67%), cerebellar atrophy (50%), nystagmus (8%), dysarthria (15.38%), and visual impairment (8%). Genetic analysis confirmed ATM gene variations in 16 unrelated cases. The most common type of variation was stopgain variants (56%). Immunoglobulin profile indicated reduced IgA, IgG, and IgM in 94%, 50%, and 20% cases, respectively. T cell lymphopenia was observed in 80% of cases among those investigated. Unusual presentations included an EBV-associated smooth muscle tumour located in the liver in one case and Hyper IgM syndrome-like presentation in two cases. Increased immunosenescence was observed in T-cell subsets (CD4+CD57+ and CD8+CD57+). T-cell receptor excision circles (TRECs) were reduced in 3/8 (37.50%) cases.

Details

Title
Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India
Author
Rawat Amit 1 ; Tyagi Rahul 1 ; Chaudhary Himanshi 1 ; Pandiarajan Vignesh 1 ; Jindal, Ankur Kumar 1 ; Suri Deepti 1 ; Gupta, Anju 1 ; Sharma Madhubala 1 ; Arora Kanika 1 ; Bal Amanjit 2 ; Madaan Priyanka 3 ; Saini Lokesh 3 ; Sahu, Jitendra Kumar 3 ; Ogura Yumi 4 ; Kato Tamaki 4 ; Imai Kohsuke 5 ; Nonoyama Shigeaki 4 ; Singh, Surjit 1 

 Postgraduate Institute of Medical Education and Research (PGIMER), Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Chandigarh, India (GRID:grid.415131.3) (ISNI:0000 0004 1767 2903) 
 Postgraduate Institute of Medical Education and Research, Department of Histopathology, Chandigarh, India (GRID:grid.415131.3) (ISNI:0000 0004 1767 2903) 
 Post Graduate Institute of Medical Education and Research, Pediatric Neurology Unit, Department of Pediatrics, Chandigarh, India (GRID:grid.415131.3) (ISNI:0000 0004 1767 2903) 
 National Defense Medical College (Japan), Saitama, Japan (GRID:grid.416614.0) (ISNI:0000 0004 0374 0880) 
 National Defense Medical College (Japan), Saitama, Japan (GRID:grid.416614.0) (ISNI:0000 0004 0374 0880); Tokyo Medical and Dental University, Tokyo, Japan (GRID:grid.265073.5) (ISNI:0000 0001 1014 9130) 
Publication year
2022
Publication date
2022
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
ProQuest document ID
2637589393
Copyright
© The Author(s) 2022. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.