2. Academic Validation
  3. A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability

A noncoding, regulatory mutation implicates HCFC1 in nonsyndromic intellectual disability

  • Am J Hum Genet. 2012 Oct 5;91(4):694-702. doi: 10.1016/j.ajhg.2012.08.011.
Lingli Huang 1,  Lachlan A Jolly,  Saffron Willis-Owen,  Alison Gardner,  Raman Kumar,  Evelyn Douglas,  Cheryl Shoubridge,  Dagmar Wieczorek,  Andreas Tzschach,  Monika Cohen,  Anna Hackett,  Michael Field,  Guy Froyen,  Hao Hu,  Stefan A Haas,  Hans-Hilger Ropers,  Vera M Kalscheuer,  Mark A Corbett,  Jozef Gecz
Affiliations

Affiliation

  • 1 Genetics and Molecular Pathology, SA Pathology, North Adelaide, SA 5006, Australia.
PMID: 23000143 DOI: 10.1016/j.ajhg.2012.08.011
Abstract

The discovery of mutations causing human disease has so far been biased toward protein-coding regions. Having excluded all annotated coding regions, we performed targeted massively parallel resequencing of the nonrepetitive genomic linkage interval at Xq28 of family MRX3. We identified in the binding site of transcription factor YY1 a regulatory mutation that leads to overexpression of the chromatin-associated transcriptional regulator HCFC1. When tested on embryonic murine neural stem cells and embryonic hippocampal neurons, HCFC1 overexpression led to a significant increase of the production of astrocytes and a considerable reduction in neurite growth. Two other nonsynonymous, potentially deleterious changes have been identified by X-exome Sequencing in individuals with intellectual disability, implicating HCFC1 in normal brain function.

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