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

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.

Infections in DNA Repair Defects

“…No patient had a cytomegalovirus infection in this cohort. In addition to chronic EBV infection, EBV-associated tumors such as smooth muscle tumors in the liver and nodular sclerosing Hodgkin lymphoma and mucosa-associated lymphoid tissue (MALT Lymphoma) in the parotid gland have been reported in AT [ 12 , 22 , 23 , 24 ]. Complications associated with live-viral vaccines for polio, measles, mumps, or varicella zoster have not been reported except for one vaccine-associated poliomyelitis case [ 25 ].…”