title: Loss-of-Function SOX10 Mutation in a Patient with Kallmann Syndrome, Hearing Loss, and Iris Hypopigmentation.
abstract: 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.
  
  
  METHODS
  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.
authors.affiliation: Department of Molecular Endocrinology, National Research Institute for Child Health and Development, Tokyo, Japan.
authors.forename: Erina
authors.initials: E
authors.lastname: Suzuki
authors.forename: Yoko
authors.initials: Y
authors.lastname: Izumi
authors.forename: Yuta
authors.initials: Y
authors.lastname: Chiba
authors.forename: Reiko
authors.initials: R
authors.lastname: Horikawa
authors.forename: Yoichi
authors.initials: Y
authors.lastname: Matsubara
authors.forename: Mamoru
authors.initials: M
authors.lastname: Tanaka
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Ogata
authors.forename: Maki
authors.initials: M
authors.lastname: Fukami
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Naiki
mesh_terms: D002648:Child; D005091:Exons / Q000235:genetics; D005640:Follicle Stimulating Hormone / Q000097:blood; D034381:Hearing Loss / Q000150:complications / Q000235:genetics*; D006801:Humans; D017496:Hypopigmentation / Q000150:complications / Q000235:genetics; D007499:Iris Diseases / Q000150:complications / Q000235:genetics*; D017436:Kallmann Syndrome / Q000150:complications / Q000235:genetics*; D008297:Male; D020125:Mutation, Missense; D055757:SOXE Transcription Factors / Q000235:genetics*; D012741:Sexual Maturation; D013739:Testosterone / Q000097:blood
chemical_list: C527923:SOX10 protein, human; D055757:SOXE Transcription Factors; D013739:Testosterone; D005640:Follicle Stimulating Hormone