Supplementary Material for: Loss-of-Function SOX10 Mutation in a Patient with Kallmann Syndrome, Hearing Loss, and Iris Hypopigmentation

<b><i>Background:</i></b> Kallmann syndrome (KS) is a clinically and genetically heterogeneous disorder consisting of hypogonadotropic hypogonadism and anosmia. KS is occasionally associated with deafness. Recently, mutations in <i>SOX10</i>, a well-known causative gene of Waardenburg syndrome (WS) characterized by deafness, skin/hair/iris hypopigmentation, Hirschsprung disease, and neurological defects, have been identified in a few patients with KS and deafness. However, the current understanding of the clinical consequences of <i>SOX10</i> mutations remains fragmentary. <b><i>Case Report:</i></b> A Japanese male patient presented with sensory deafness, blue irises, and anosmia, but no hair/skin hypopigmentation, Hirschsprung disease, or neurological abnormalities. He showed no pubertal sex development at 15.1 years of age. Blood examinations revealed low levels of FSH and testosterone. <b><i>Results:</i></b> Molecular analysis detected a de novo p.Leu145Pro mutation in <i>SOX10</i>, which has previously been reported in a patient with WS and Hirschsprung disease. The mutation was predicted to be probably damaging. The mutant protein barely exerted in vitro transactivating activity. <b><i>Conclusions:</i></b> These results highlight the significance of <i>SOX10</i> haploinsufficiency as a genetic cause of KS with deafness. Importantly, our data imply that the same <i>SOX10</i> mutations can underlie both typical WS and KS with deafness without skin/hair hypopigmentation, Hirschsprung disease, or neurological defects.