Delmaghani et al. (2012) studied a 6-generation consanguineous Iranian family in which 3 brothers, born of first-cousin parents, had nonsyndromic prelingual sensorineural deafness. The affected sibs, aged 20 to 34 years, had severely impaired language acquisition; pure-tone audiometry ... Delmaghani et al. (2012) studied a 6-generation consanguineous Iranian family in which 3 brothers, born of first-cousin parents, had nonsyndromic prelingual sensorineural deafness. The affected sibs, aged 20 to 34 years, had severely impaired language acquisition; pure-tone audiometry showed flat audiograms, characteristic of profound hearing impairment. No auditory brain response (ABR) could be recorded even in response to 100-dB sound stimulation in any of the affected brothers, indicating defects of the cochlea or the auditory nerve. In addition, ipsilateral stapedial reflexes were absent, and transient-evoked otoacoustic emissions to probe the activity of outer hair cells could not be detected.
In an affected sib from a 6-generation consanguineous Iranian family segregating autosomal recessive nonsyndromic prelingual sensorineural deafness mapping to chromosome 21q22, Delmaghani et al. (2012) sequenced the candidate gene TMPRSS3, but did not detect any causative mutation. Whole-exome ... In an affected sib from a 6-generation consanguineous Iranian family segregating autosomal recessive nonsyndromic prelingual sensorineural deafness mapping to chromosome 21q22, Delmaghani et al. (2012) sequenced the candidate gene TMPRSS3, but did not detect any causative mutation. Whole-exome sequencing focusing on exonic and flanking intronic variants between nucleotide positions 43,341,362 and 48,084,747 (GRCh37) revealed 2 adjacent variants in the TSPEAR gene (612920.0001) for which the 3 affected brothers were homozygous and their unaffected parents and 2 unaffected sisters were heterozygous. Analysis of the TSPEAR gene in 55 other large Iranian families affected by deafness did not reveal any additional mutations.