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.

Tracheoesophageal speech in a developing world community.

OBJECTIVES: To determine the tracheoesophageal speech results in a Third World medical practice; to examine the impact of socioeconomic status, literacy, and proximity to specialist services on tracheoesophageal speech; to assess whether these factors should affect patient selection for fistula speech; and to determine guidelines for voice prosthesis selection. DESIGN: Retrospective analysis. SETTING: Groote Schuur Hospital, Cape Town, South Africa, which serves a Third World community. PATIENTS: Ninety-seven consecutive patients who underwent total laryngectomy between January 1, 1996, and October 1, 1998. Patients who undergo total laryngectomy routinely have a primary tracheoesophageal fistula created for speech. MAIN OUTCOME MEASURES: Speech outcomes after total laryngectomy; tracheoesophageal speech in relation to social class, literacy, and proximity to specialist services; and experience with removable and indwelling valves. RESULTS: Fifty-nine (81%) of 73 patients acquired useful speech. Speech outcome was not affected by employment status or proximity to specialist services. Although speech was affected by literacy and housing, several illiterate shack dwellers acquired good speech. Average device life of removable prostheses was 16 weeks (>4 months in 35% [64/183]). Indwelling prostheses had an average life of 28 weeks. CONCLUSIONS: Tracheoesophageal speech results in a Third World community equate with those in the Developed World. All patients who undergo laryngectomy and have adequate manual dexterity and cognitive function should be given a trial of fistula speech. Removable voice prostheses can successfully be used as indwelling prostheses.