Clin Genet 2012 Printed in Singapore. All rights reserved  2012 John Wiley & Sons A/S CLINICAL GENETICS doi: 10.1111/j.1399-0004.2012.01891.x Short Report Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss Mohebbi N, Vargas-Poussou R, Hegemann SCA, Schuknecht B, Kistler AD, W¨ uthrich RP, Wagner CA. Homozygous and compound heterozygous mutations in the ATP6V1B1 gene in patients with renal tubular acidosis and sensorineural hearing loss. Clin Genet 2012.  John Wiley & Sons A/S, 2012 Distal renal tubular acidosis (dRTA) is characterized by the inability to excrete acid in the renal collecting ducts resulting in inappropriately alkaline urine and hyperchloremic (normal anion gap) metabolic acidosis in the context of a normal (or near-normal) glomerular filtration rate. Inborn dRTA can be due to autosomal dominant or recessive gene defects. Clinical symptoms vary from mild acidosis, incidental detection of kidney stones or renal tract calcification to severe findings such as failure to thrive, severe metabolic acidosis, and nephrocalcinosis. The majority of patients with recessive dRTA present with sensorineural hearing loss (SNHL). Few cases with abnormal widening of the vestibular aqueduct have been described with dRTA. Mutations in three different genes have been identified, namely SLC4A1, ATP6V1B1, and ATP6V0A4. Patients with mutations in the ATP6V1B1 proton pump subunit develop dRTA and in most of the cases sensorineural hearing loss early in childhood. We present two patients from two different and non-consanguineous families with dRTA and SNHL. Direct sequencing of the ATP6V1B1 gene revealed that one patient harbors two homozygous mutations and the other one is a compound heterozygous. To our knowledge, this is the first case in the literature describing homozygosity in the same dRTA gene on both alleles. Conflict of interest The authors have no conflicts of interest to disclose. N Mohebbi a,b , R Vargas-Poussou c , SCA Hegemann d , B Schuknecht e , AD Kistler b , RP W ¨ uthrich b and CA Wagner a a Institute of Physiology and Zurich Center for Integrative Human Physiology (ZIHP), University of Zurich, Zurich, Switzerland, b Division of Nephrology, University Hospital Zurich, Zurich, Switzerland, c D´ epartement de G ´ en ´ etique, Assistance Publique-H ˆ opitaux de Paris, H ˆ opital Europ ´ een Georges Pompidou, Paris, France, d Department of Otorhinolaryngology, Head & Neck Surgery, University Hospital Zurich, Zurich, Switzerland, and e Department of Neuroradiology, Institute for Medical Radiology, Zurich, Switzerland Key words: deafness – distal renal tubular acidosis – enlarged vestibular aqueduct – proton pump Corresponding author: Nilufar Mohebbi, Institute of Physiology, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland. Tel.: +41 44 63 55036; fax: +41 44 63 56814; e-mail: nmohebbi@access.uzh.ch Received 7 February 2012, revised and accepted for publication 11 April 2012 Patients Case I The 25-year-old woman was admitted at the age of 4 months to the Hospital because of vomiting and failure to thrive. The patients’ family originates from Kosovo and is not consanguineous (Fig. 1a). Distal RTA was diagnosed and treated with sodium bicarbon- ate and potassium citrate. At the age of 3.5 years, brain stem evoked response audiometry revealed bilateral SNHL and hearing aids were introduced. She showed neither episodes of kidney stones nor pyelonephri- tis. At the age of 14 years, she started suffering from occasional attacks of rotatory vertigo. High- resolution computed tomography (HR-CT) and mag- netic resonance imaging (MRI) of the temporal bones confirmed enlarged vestibular aqueduct (EVA) syn- drome on the left side (Fig. 2). She has two brothers 1