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

. 2022 Mar 8;12(1):4036.
 doi: 10.1038/s41598-022-08019-0.

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

Amit Rawat#rawatamit@yahoo.com.">1, Rahul Tyagi#2, Himanshi Chaudhary2, Vignesh Pandiarajan2, Ankur Kumar Jindal2, Deepti Suri2, Anju Gupta2, Madhubala Sharma2, Kanika Arora2, Amanjit Bal3, Priyanka Madaan4, Lokesh Saini4, Jitendra Kumar Sahu4, Yumi Ogura5, Tamaki Kato5, Kohsuke Imai56, Shigeaki Nonoyama5, Surjit Singh2
Affiliations 

Affiliations

  • 1Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India. rawatamit@yahoo.com.
  • 2Allergy and Immunology Laboratory, Department of Pediatrics, Advanced Pediatric Centre, Postgraduate Institute of Medical Education and Research (PGIMER), Chandigarh, 160012, India.
  • 3Department of Histopathology, Postgraduate Institute of Medical Education and Research, Chandigarh, India.
  • 4Pediatric Neurology Unit, Department of Pediatrics, Post Graduate Institute of Medical Education and Research, Chandigarh, India.
  • 5National Defense Medical College (Japan), Saitama, Japan.
  • 6Tokyo Medical and Dental University, Tokyo, Japan.
#Contributed equally.
    • PMID: 35260754
    Free PMC article

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.