Localization of a gene for autosomal recessive distal renal tubular acidosis with normal hearing (rdRTA2) to 7q33-34.

Karet, F E; Finberg, K E; Nayir, A; Bakkaloglu, A; Ozen, S; Hulton, S A; Sanjad, S A; Al-Sabban, E A; Medina, J F; Lifton, R P

Karet, F E; Finberg, K E; Nayir, A; Bakkaloglu, A; Ozen, S; Hulton, S A; Sanjad, S A; Al-Sabban, E A; Medina, J F; Lifton, R P.

Afiliación

Karet FE; Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 2XY, United Kingdom. fek1000@hermes.cam.ac.uk.

Am J Hum Genet ; 65(6): 1656-65, 1999 Dec.

Article en En | MEDLINE | ID: mdl-10577919

RESUMEN

Failure of distal nephrons to excrete excess acid results in the "distal renal tubular acidoses" (dRTA). Early childhood features of autosomal recessive dRTA include severe metabolic acidosis with inappropriately alkaline urine, poor growth, rickets, and renal calcification. Progressive bilateral sensorineural hearing loss (SNHL) is evident in approximately one-third of patients. We have recently identified mutations in ATP6B1, encoding the B-subunit of the collecting-duct apical proton pump, as a cause of recessive dRTA with SNHL. We now report the results of genetic analysis of 13 kindreds with recessive dRTA and normal hearing. Analysis of linkage and molecular examination of ATP6B1 indicated that mutation in ATP6B1 rarely, if ever, accounts for this phenotype, prompting a genomewide linkage search for loci underlying this trait. The results strongly supported linkage with locus heterogeneity to a segment of 7q33-34, yielding a maximum multipoint LOD score of 8.84 with 68% of kindreds linked. The LOD-3 support interval defines a 14-cM region flanked by D7S500 and D7S688. That 4 of these 13 kindreds do not support linkage to rdRTA2 and ATP6B1 implies the existence of at least one additional dRTA locus. These findings establish that genes causing recessive dRTA with normal and impaired hearing are different, and they identify, at 7q33-34, a new locus, rdRTA2, for recessive dRTA with normal hearing.

Asunto(s)

Acidosis Tubular Renal/genética; Proteínas de Transporte de Anión; Antiportadores; Mapeo Cromosómico; Cromosomas Humanos Par 7/genética; Genes Recesivos/genética; Audición/fisiología; Acidosis Tubular Renal/fisiopatología; Adenosina Trifosfatasas/genética; Adulto; Niño; Preescolar; Cromosomas Humanos Par 2/genética; Consanguinidad; Análisis Mutacional de ADN; Femenino; Audición/genética; Humanos; Concentración de Iones de Hidrógeno; Lactante; Recién Nacido; Escala de Lod; Masculino; Proteínas de la Membrana/genética; Medio Oriente; Datos de Secuencia Molecular; Pakistán; Linaje; Polimorfismo Conformacional Retorcido-Simple; Proteínas SLC4A

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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Acidosis Tubular Renal / Cromosomas Humanos Par 7 / Mapeo Cromosómico / Antiportadores / Proteínas de Transporte de Anión / Genes Recesivos / Audición Tipo de estudio: Prognostic_studies Límite: Adult / Child / Child, preschool / Female / Humans / Infant / Male / Newborn País/Región como asunto: Asia Idioma: En Revista: Am J Hum Genet Año: 1999 Tipo del documento: Article País de afiliación: Reino Unido Pais de publicación: Estados Unidos

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