• PMID: 26228106
• Gene Name: SOX10
• Condition: Kallmann syndrome
• Association: Molecular analysis detected a de novo p.Leu145Pro mutation in SOX10, 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 transacti
• Mutation: p.Leu145Pro
• Population size: 1
• Population details: 1
• Age: 15.1 years
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Male infertility

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

Suzuki E, Izumi Y, Chiba Y, Horikawa R, Matsubara Y, Tanaka M, Ogata T, Fukami M, Naiki Y.

BACKGROUND: 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 SOX10, 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 SOX10 mutations remains fragmentary. CASE REPORT: 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. RESULTS: Molecular analysis detected a de novo p.Leu145Pro mutation in SOX10, 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. CONCLUSIONS: These results highlight the significance of SOX10 haploinsufficiency as a genetic cause of KS with deafness. Importantly, our data imply that the same SOX10 mutations can underlie both typical WS and KS with deafness without skin/hair hypopigmentation, Hirschsprung disease, or neurological defects. CI - © 2015 S. Karger AG, Basel. FAU - Suzuki, Erina AU - Suzuki E AD - Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan. FAU - Izumi, Yoko AU - Izumi Y FAU - Chiba, Yuta AU - Chiba Y FAU - Horikawa, Reiko AU - Horikawa R FAU - Matsubara, Yoichi AU - Matsubara Y FAU - Tanaka, Mamoru AU - Tanaka M FAU - Ogata, Tsutomu AU - Ogata T FAU - Fukami, Maki AU - Fukami M