Hypogonadotropic hypogonadism in a female patient previously diagnosed as having waardenburg syndrome due to a sox10 mutation

Excerpt

Hypogonadotropic hypogonadism (HH) is a clinically and genetically heterogeneous condition that can be associated with several additional clinical features such as anosmia, cleft palate, and hearing loss [1]. HH with anosmia is referred to as Kallmann syndrome (KS). More than 20 genes are known to underlie HH and/or KS, although mutations in these genes account for only a minor portion of the etiology of HH/KS [1‐4]. In 2013, Pingault et al. identified SOX10 mutations in seven patients with KS [5]. Furthermore, Pingault et al. found that genetic knockout of Sox10 disrupted migration of GnRH cells in murine fetuses [5]. Subsequently, Vaaralahti et al. identified an additional KS patient with a SOX10 mutation [6]. These results indicate that SOX10 mutations constitute rare genetic causes of KS. Currently, SOX10 is known as one of the causative genes of Waardenburg syndrome (WS), a rare genetic disorder characterized by hearing loss and hypopigmentation in the skin, hair, and eye [7]. Indeed, hearing impairment with or without gray/white hair was found in most of the KS cases reported by Pingault et al. and Vaaralahti et al. [5, 6]. However, detailed clinical assessment of the SOX10 mutation-positive patients and functional assays of the SOX10 mutants remain fragmentary. Thus, genetic links between HH/KS and WS have not been fully established. Here, we performed molecular and clinical analyses of a previously reported patient with WS due to a frameshift mutation in SOX10. …