A Clinical Conundrum with Diagnostic and Therapeutic Challenge: a Tale of Two Disorders in One Case.
Pallavi GaikwadUmair Ahmed BargirShweta ShindePranoti KiniRajesh ChaurasiaUsha YadavAmruta DhawaleMerin GeorgeNeha JodhawatPriyanka SetiaDisha VedpathakAparna DalviAnkita ParabMaya GuptaReetika Malik YadavMayuri GoriwaleBaburao VundintiNagesh BhatB K SapraMadhumati OtivRatna SharmaManisha Rajan MadkaikarPublished in: Journal of clinical immunology (2023)
Living organisms are exposed to exogenous and endogenous agents that affect genomic integrity by creating DNA double strand breaks (DSBs). These breaks are repaired by DNA repair proteins to maintain homeostasis. Defects in DNA repair pathways also affect lymphocyte development and maturation, as DSB sites are critical intermediates for rearrangements required for V(D)J recombination. Recent classifications for inborn errors of immunity (IEIs) have listed DNA repair defect genes in a separate group, which suggests the importance of these genes for adaptive and innate immunity. We report an interesting case of a young female (index P1) with mutations in two different genes, DCLRE1C and FANCA, involved in DNA repair pathways. She presented with clinical manifestations attributed to both defects. With the advent of NGS, more than one defect is increasingly identified in patients with IEIs. Familial segregation studies and appropriate functional assays help ascertain the pathogenicity of these mutations and provide appropriate management and genetic counseling.
Keyphrases
- dna repair
- dna damage
- genome wide
- dna damage response
- genome wide identification
- bioinformatics analysis
- copy number
- genome wide analysis
- gene expression
- early onset
- patient safety
- escherichia coli
- emergency department
- oxidative stress
- high throughput
- smoking cessation
- peripheral blood
- adverse drug
- human immunodeficiency virus
- antiretroviral therapy
- drug induced
- soft tissue
- candida albicans