Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency

Frederic Laumonnier, Nathalie Ronce, Ben C.J. Hamel, Paul Thomas, James Lespinasse, Martine Raynaud, Christine Paringaux, Hans Van Bokhoven, Vera Kalscheuer, Jean Pierre Fryns, Jamel Chelly, Claude Moraine, Sylvain Briault

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212 Citations (Scopus)

Abstract

Physical mapping of the breakpoints of a pericentric inversion of the X chromosome (46,X,inv[X][p21q27]) in a female patient with mild mental retardation revealed localization of the Xp breakpoint in the IL1RAPL gene at Xp21.3 and the Xq breakpoint near the SOX3 gene (SRY [sex determining region Y]-box 3) (GenBank accession number NM_005634) at Xq26.3. Because carrier females with microdeletion in the IL1RAPL gene do not present any abnormal phenotype, we focused on the Xq breakpoint. However, we were unable to confirm the involvement of SOX3 in the mental retardation in this female patient. To validate SOX3 as an X-linked mental retardation (XLMR) gene, we performed mutation analyses in families with XLMR whose causative gene mapped to Xq26-q27. We show here that the SOX3 gene is involved in a large family in which affected individuals have mental retardation and growth hormone deficiency. The mutation results in an in-frame duplication of 33 bp encoding for 11 alanines in a polyalanine tract of the SOX3 gene. The expression pattern during neural and pituitary development suggests that dysfunction of the SOX3 protein caused by the polyalanine expansion might disturb transcription pathways and the regulation of genes involved in cellular processes and functions required for cognitive and pituitary development.

LanguageEnglish
Pages1450-1455
Number of pages6
JournalAmerican Journal of Human Genetics
Volume71
Issue number6
DOIs
Publication statusPublished - 1 Dec 2002

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Laumonnier, F., Ronce, N., Hamel, B. C. J., Thomas, P., Lespinasse, J., Raynaud, M., ... Briault, S. (2002). Transcription factor SOX3 is involved in X-linked mental retardation with growth hormone deficiency. American Journal of Human Genetics, 71(6), 1450-1455. https://doi.org/10.1086/344661