Unusual clinical manifestations and predominant stopgain ATM gene variants in a single centre cohort of ataxia telangiectasia from North India

• Published in: Scientific reports Vol. 12; no. 1; p. 4036
• Main Authors: Rawat, Amit, Tyagi, Rahul, Chaudhary, Himanshi, Pandiarajan, Vignesh, Jindal, Ankur Kumar, Suri, Deepti, Gupta, Anju, Sharma, Madhubala, Arora, Kanika, Bal, Amanjit, Madaan, Priyanka, Saini, Lokesh, Sahu, Jitendra Kumar, Ogura, Yumi, Kato, Tamaki, Imai, Kohsuke, Nonoyama, Shigeaki, Singh, Surjit
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 08.03.2022; Nature Publishing Group; Nature Portfolio
• Subjects: 631/208; 631/208/1516; 631/208/2489; 631/208/514; 631/250; 631/250/248; 631/250/249; 692/617; Ataxia; Ataxia telangiectasia; Ataxia Telangiectasia - genetics; Ataxia telangiectasia mutated protein; Ataxia Telangiectasia Mutated Proteins - genetics; Atrophy; CD4 antigen; CD57 antigen; CD8 antigen; Cerebellum; Fever; Genetic analysis; Heterogeneity; Humanities and Social Sciences; Humans; Hyper-IgM Immunodeficiency Syndrome; Immunoglobulin A; Immunoglobulin G; Immunoglobulin M; Immunosenescence; Lymphocytes T; Lymphopenia; multidisciplinary; Mutation; Nystagmus; Phenotypic variations; Retrospective Studies; Science; Science (multidisciplinary); Smooth muscle; T cell receptors; T-Lymphocyte Subsets; Tumors
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/s41598-022-08019-0

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.