Renal dysfunction, rod-cone dystrophy, and sensorineural hearing loss caused by a mutation in RRM2B.

More than two decades ago, a recessive syndromic phenotype affecting kidneys, eyes, and ears, was first described in the endogamous Afrikaner population of South Africa. Using whole-exome sequencing of DNA from two affected siblings (and their carrier parents), we identified the novel RRM2B c.786G>T variant as a plausible disease-causing mutation. The RRM2B gene is involved in mitochondrial integrity, and the observed change was not previously reported in any genomic database. The subsequent screening revealed the variant in two newly presenting unrelated patients, as well as two patients in our registry with rod-cone dystrophy, hearing loss, and Fanconi-type renal disease. All patients with the c.786G>T variant share an identical 1.5 Mb haplotype around this gene, suggesting a founder effect in the Afrikaner population. We present ultrastructural evidence of mitochondrial impairment in one patient, to support our thesis that this RRM2B variant is associated with the renal, ophthalmological, and auditory phenotype.

Childhood helminth exposure is protective against inflammatory bowel disease: a case control study in South Africa.

BACKGROUND: Inflammatory bowel disease (IBD) is more common in countries with improved hygiene, suggesting that environmental exposures may be associated with its development. The primary objective of this study was to examine the association between self-reported childhood helminth infection and the development of IBD in South Africa. METHODS: Unmatched case-control study. Logistic regression was used to model associations with IBD. RESULTS: There were 88 patients with Crohn's disease (CD), 63 with ulcerative colitis (UC), and 219 control subjects. Of the 151, 93 (61.6%) IBD subjects (35 of 63 [55.6%] had UC and 58 of 88 [65.9%] had CD) reported childhood helminth exposure compared with 200 of 219 (91.3%) non-IBD subjects (P < 0.001). Helminth infection (adjusted odds ratio [AOR] = 0.2; 95% confidence interval [CI], 0.1-0.4), shared housing (AOR = 0.1; 95% CI, 0.04-0.4), and raw beef consumption (AOR = 0.2; 95% CI, 0.1-0.6) were protective, whereas urban dwelling (AOR = 4.2; 95% CI, 2.0-8.8) and parental tertiary education (AOR = 18.2; 95% CI, 3.2-103.7) were associated with CD. Helminth infection (AOR = 0.2; 95% CI, 0.1-0.6), mixed race (AOR = 0.1; 95% CI, 0.03-0.5), smoking (AOR = 0.2; 95% CI, 0.07-0.5), shared housing (AOR = 0.1; 95% CI, 0.01-0.4), and raw beef consumption (AOR = 0.1; 95% CI 0.04-0.5) were protective against UC, whereas parental tertiary education (AOR = 12.7; 95% CI, 1.0-157.4) was associated with UC. CONCLUSION: This study demonstrates a protective association of childhood helminth infection against the development of IBD and supports the "hygiene hypothesis" that improved living conditions may increase the incidence of IBD. Our epidemiologic conclusions provide support that helminths may have immunomodulatory effects which provides protection against the development of IBD later in life.