Basit et al. (2011) reported 2 unrelated consanguineous Pakistani families with autosomal recessive nonsyndromic moderate to severe hearing loss affecting all frequencies. The onset of deafness was prelingual, and there was no apparent vestibular involvement.
Santos-Cortez ... Basit et al. (2011) reported 2 unrelated consanguineous Pakistani families with autosomal recessive nonsyndromic moderate to severe hearing loss affecting all frequencies. The onset of deafness was prelingual, and there was no apparent vestibular involvement. Santos-Cortez et al. (2013) provided follow-up on the 2 Pakistani families with nonsyndromic deafness originally reported by Basit et al. (2011) (families 4338 and 4406), and described a third consanguineous Pakistani family (4284) with nonsyndromic deafness showing linkage to the DFNB89 locus. Santos-Cortez et al. (2013) noted that there were no other syndromic, vestibular, neurologic, or systemic abnormalities detected on physical examination of affected individuals in the 3 families. Air-conduction audiometry in 1 affected individual from each family showed symmetric bilateral severe to profound hearing impairment in the patients from families 4284 and 4338, and symmetric moderate to severe hearing impairment across all frequencies tested in the patient from family 4406.
Santos-Cortez et al. (2013) performed whole-exome sequencing in 1 affected individual from each of 3 consanguineous Pakistani families with nonsyndromic deafness mapping to chromosome 16q21-q23.2, 2 of which had previously been studied by Basit et al. (2011), and ... Santos-Cortez et al. (2013) performed whole-exome sequencing in 1 affected individual from each of 3 consanguineous Pakistani families with nonsyndromic deafness mapping to chromosome 16q21-q23.2, 2 of which had previously been studied by Basit et al. (2011), and identified 2 homozygous missense mutations in the KARS gene: 2 probands were homozygous for a Y173H substitution (601421.0003), and 1 was homozygous for a D377N substitution (601421.0004). Sequencing confirmed that both KARS variants segregated with disease in the respective families, and neither was found in 325 ethnically matched controls or in variant databases. Noting that compound heterozygosity for KARS mutations had previously been identified in a patient with a form of Charcot-Marie-Tooth disease (613641) and bilateral acoustic neuroma, Santos-Cortez et al. (2013) performed additional examinations in 3 affected individuals from 2 of the families but found no evidence for auditory or limb neuropathy in the DFNB89 patients.