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Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.


ABSTRACT: SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5. Common features in these subjects include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions may depend on the location of the deletion and, consequently, which of the three major SOX5 protein isoforms are affected. One intragenic deletion, involving only untranslated exons, was present in a more mildly affected subject, was inherited from a healthy parent and grandparent, and is similar to a deletion found in a control cohort. Therefore, some intragenic SOX5 deletions may have minimal phenotypic effect. Based on the location of the deletions in the subjects compared to the controls, the de novo nature of most of these deletions, and the phenotypic similarities among cases, SOX5 appears to be a dosage-sensitive, developmentally important gene.

SUBMITTER: Lamb AN 

PROVIDER: S-EPMC3618980 | biostudies-literature | 2012 Apr

REPOSITORIES: biostudies-literature

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Haploinsufficiency of SOX5 at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features.

Lamb Allen N AN   Rosenfeld Jill A JA   Neill Nicholas J NJ   Talkowski Michael E ME   Blumenthal Ian I   Girirajan Santhosh S   Keelean-Fuller Debra D   Fan Zheng Z   Pouncey Jill J   Stevens Cathy C   Mackay-Loder Loren L   Terespolsky Deborah D   Bader Patricia I PI   Rosenbaum Kenneth K   Vallee Stephanie E SE   Moeschler John B JB   Ladda Roger R   Sell Susan S   Martin Judith J   Ryan Shawnia S   Jones Marilyn C MC   Moran Rocio R   Shealy Amy A   Madan-Khetarpal Suneeta S   McConnell Juliann J   Surti Urvashi U   Delahaye Andrée A   Heron-Longe Bénédicte B   Pipiras Eva E   Benzacken Brigitte B   Passemard Sandrine S   Verloes Alain A   Isidor Bertrand B   Le Caignec Cedric C   Glew Gwen M GM   Opheim Kent E KE   Descartes Maria M   Eichler Evan E EE   Morton Cynthia C CC   Gusella James F JF   Schultz Roger A RA   Ballif Blake C BC   Shaffer Lisa G LG  

Human mutation 20120401 4


SOX5 encodes a transcription factor involved in the regulation of chondrogenesis and the development of the nervous system. Despite its important developmental roles, SOX5 disruption has yet to be associated with human disease. We report one individual with a reciprocal translocation breakpoint within SOX5, eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent), and seven individuals with larger 12p12 deletions encompassing SOX5.  ...[more]

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