RGD Reference Report - Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness. - Rat Genome Database

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Loss-of-function mutations in SOX10 cause Kallmann syndrome with deafness.

Authors: Pingault, Veronique  Bodereau, Virginie  Baral, Viviane  Marcos, Severine  Watanabe, Yuli  Chaoui, Asma  Fouveaut, Corinne  Leroy, Chrystel  Vérier-Mine, Odile  Francannet, Christine  Dupin-Deguine, Delphine  Archambeaud, Françoise  Kurtz, François-Joseph  Young, Jacques  Bertherat, Jérôme  Marlin, Sandrine  Goossens, Michel  Hardelin, Jean-Pierre  Dodé, Catherine  Bondurand, Nadege 
Citation: Pingault V, etal., Am J Hum Genet. 2013 May 2;92(5):707-24. doi: 10.1016/j.ajhg.2013.03.024.
RGD ID: 12832748
Pubmed: PMID:23643381   (View Abstract at PubMed)
PMCID: PMC3644631   (View Article at PubMed Central)
DOI: DOI:10.1016/j.ajhg.2013.03.024   (Journal Full-text)

Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.

RGD Manual Disease Annotations    Click to see Annotation Detail View

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
SOX10HumanKallmann syndrome  IAGP DNA:mutations:cds:RGD 
Sox10RatKallmann syndrome  ISOSOX10 (Homo sapiens)DNA:mutations:cds:RGD 
Sox10MouseKallmann syndrome  ISOSOX10 (Homo sapiens)DNA:mutations:cds:RGD 

Objects Annotated

Genes (Rattus norvegicus)
Sox10  (SRY-box transcription factor 10)

Genes (Mus musculus)
Sox10  (SRY (sex determining region Y)-box 10)

Genes (Homo sapiens)
SOX10  (SRY-box transcription factor 10)

Additional Information