Haploinsufficiency ofSOX5at 12p12.1 is associated with developmental delays with prominent language delay, behavior problems, and mild dysmorphic features
- 30 January 2012
- journal article
- research article
- Published by Hindawi Limited in Human Mutation
- Vol. 33 (4), 728-740
- https://doi.org/10.1002/humu.22037
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. Hum Mutat 33:728–740, 2012.This publication has 56 references indexed in Scilit:
- Transcriptional Regulation of an Axonemal Central Apparatus Gene, Sperm-associated Antigen 6, by a SRY-related High Mobility Group Transcription Factor, S-SOX5Online Journal of Public Health Informatics, 2010
- Phenotypic variability and genetic susceptibility to genomic disordersHuman Molecular Genetics, 2010
- Deletion and Point Mutations of PTHLH Cause Brachydactyly Type EAmerican Journal of Human Genetics, 2010
- The TEACCH Program in the Era of Evidence-Based PracticeJournal of Autism and Developmental Disorders, 2009
- Generation of mice harboring aSox5conditional null allelegenesis, 2008
- SOX5 Controls the Sequential Generation of Distinct Corticofugal Neuron SubtypesNeuron, 2008
- Identification and analysis of functional elements in 1% of the human genome by the ENCODE pilot projectNature, 2007
- Genome-wide Map of Nucleosome Acetylation and Methylation in YeastCell, 2005
- Histone H3 lysine 4 methylation patterns in higher eukaryotic genesNature, 2003
- Lysine-79 of histone H3 is hypomethylated at silenced loci in yeast and mammalian cells: A potential mechanism for position-effect variegationProceedings of the National Academy of Sciences of the United States of America, 2003