Functional analysis of SOX10 mutations identified in Chinese patients with Kallmann syndrome

Kallmann syndrome (KS) is characterized by the association of anosmia and hypogonadotropic hypogonadism. The hypogonadotropic hypogonadism is due to deficient production, secretion or action of gonadotropin-releasing hormone (GnRH). Mutations in transcription factor SOX10 have been recently identified in patients with KS and hearing loss. In this study, we identified three novel SOX10 mutations in a cohort of Chinese KS patients by using exome sequencing. Two mutations (A44G and L80V) are in heterozygous state whereas the other one (G41V) is a homozygous mutation. The patient with a homozygous G41V mutation had impaired hearing in both ears, whereas the patient with a heterozygous L80V mutation showed subtle hearing impairment in the left ear. Functional studies indicated that all three SOX10 mutations showed reduced capacity to transactivate the MITF promoter alone or in synergy with PAX3, although they showed similar subcellular localization, and DNA binding ability. Our study further highlighted the significance of SOX10 haploinsufficiency as a genetic cause of KS with hearing problem. •We have identified three novel SOX10 mutations in a cohort of Chinese KS patients by using exome sequencing.•Two patients with SOX10 mutations showed hearing impairment.•All three SOX10 mutations showed reduced capacity to transactivate the MITF promoter alone or in synergy with PAX3.