Table 1.

DNA repair deficiency-induced immunological disorders.

Pathway	Disease	Genes	Description	Refs
V(D)J Recombination	Severe Combined Immunodeficiency (SCID)	RAG1, RAG2, DCLRE1C, PRKDC, NHEJ1, LIG4	SCID patients have T and B lymphocyte deficiency. At least 4 diseases can be distinguished by clinical phenotypes and the gene affected.	(18)
V(D)J Recombination	SCID with ARTEMIS deficiency	DCLRE1C	Subclinical immunodeficiency: reduction of naïve T cells with increased terminally differentiated T cells due to a reduction in T-cell proliferation. Some patients have reduced B-cell numbers.	(29)
			Hypomorphic mutations in DCLRE1C can cause atypical SCID, Omenn syndrome, Hyper IgM syndrome, or inflammatory bowel disease.
V(D)J Recombination	SCID with Ligase IV deficiency	LIG4	Microcephaly and neurodevelopmental delay.	(30)
			T- and B-lymphocytopenia and varying degrees of hypogammaglobulinaemia often associated with high IgM due to defective CSR. Some patients present with features of Omenn’s syndrome and autoimmunity.
V(D)J Recombination	SCID with Cernunnos-XLF deficiency	XLF	T and B-cell lymphopenia, growth retardation, microcephaly, and increased sensitivity to ionizing radiation.	(31)
V(D)J Recombination	SCID with DNA-PKcs deficiency	PRKDC	Radiosensitive, growth retardation, microcephaly, and immunodeficiency due to profound T and B cell lymphopenia.	(32, 33)
V(D)J Recombination	Ataxia Telangiectasia (A-T)	ATM	Progressive cerebellar degeneration leading to ataxia, telangiectasia*, immunoglobulin deficiency (IgA), lymphopenia (T cells), recurrent sinopulmonary infections, radiation sensitivity, premature aging, and a predisposition to cancer, especially lymphomas.	(34)
			Other abnormalities include poor growth, gonadal atrophy, delayed puberty, and insulin resistance, ataxia: abnormal control of eye movement and postural instability.
			Telangiectasia: abnormal, tortuous blood vessels
			(*telangiectasia not present in all A-T patients)
V(D)J Recombination and, CSR	Ataxia Telangiectasia-like disorder (ATLD)	MRE11	Lack of specific functional antibodies causing minimal immunodeficiency, ataxia, and dysarthria.	(35)
V(D)J Recombination	Nijmegen breakage syndrome	NBN	Progressive microcephaly presenting in utero, dysmorphic facial features, mild growth retardation, mild-to-moderate intellectual disability, and, in females, hypergonadotropic hypogonadism.	(36, 37)
			Immunodeficiency (decreased T cells and reduced IgG/IgA) and a high incidence of pediatric malignancies, mostly lymphomas and leukemias.
CSR and NHEJ	RIDDLE syndrome	RNF168	Radiosensitivity, Immunodeficiency, Dysmorphic features, and Learning difficulties, increased serum IgM and reduced IgG levels.	(38, 39)
CSR, SHM, BER	Hyper IgM Syndrome Type 5	UNG	Elevated serum IgM with low IgG and IgA, increased susceptibility to bacterial infections and lymphoid hyperplasia.	(40)
CSR and SHM	Hyper IgM Syndrome Type 2	AICDA	Elevated serum IgM levels, low IgG, low IgA. lymphoid hyperplasia, and recurrent infections.	(41)
CSR and MMR	PMS2 or MSH6 deficiency	PMS2	Elevated serum IgM and low IgG and IgA, recurrent infections, cafe-au-lait spots. Associated with Lynch Syndrome and colorectal and endometrial cancer.	(42, 43)