title: Haploinsufficiency of SOX5, a member of the SOX (SRY-related HMG-box) family of transcription factors is a cause of intellectual disability.
abstract: Intellectual disability (ID) is a clinically and genetically heterogeneous condition; the cause is unknown in most non-specific and sporadic cases. To establish an etiological basis in those patients represents a difficult challenge. Over the last years it has become apparent that chromosomal rearrangements below the detection level of conventional karyotyping contribute significantly to the cause of ID. We present three patients with non-specific intellectual disability who all have overlapping microdeletions in the chromosomal region 12p12.1. De novo occurrence of the deletion could be proven in the two cases from which parental samples were available. All three identified deletions have different breakpoints and range in size from 120 kb to 4.9 Mb. The smallest deletion helps to narrow down the critical region to a genomic segment (chr12:23,924,800-24,041,698, build 37/hg19) encompassing only one gene, SOX5. SOX5 is a member of the SOX (SRY-related HMG-box) family of transcription factors shown to play roles in chondroblast function, oligodendrocyte differentiation and migration, as well as ensuring proper development of specific neuronal cell types. Because of these biological functions, mutations in SOX5 are predicted to cause complex disease syndromes, as it is the case for other SOX genes, but such mutations have not yet been identified. Our findings indicate that haploinsufficiency of SOX5 is a cause of intellectual disability without any striking physical anomalies.
authors.affiliation: Institute of Human Genetics, University Hospital Magdeburg, Leipziger Str. 44, 39120 Magdeburg, Germany. ina.schanze@med.ovgu.de
authors.forename: Ina
authors.initials: I
authors.lastname: Schanze
authors.forename: Denny
authors.initials: D
authors.lastname: Schanze
authors.forename: Carlos A
authors.initials: CA
authors.lastname: Bacino
authors.forename: Sofia
authors.initials: S
authors.lastname: Douzgou
authors.forename: Bronwyn
authors.initials: B
authors.lastname: Kerr
authors.forename: Martin
authors.initials: M
authors.lastname: Zenker
mesh_terms: D002648:Child; D002675:Child, Preschool; D002881:Chromosomes, Human, Pair 12; D055028:Comparative Genomic Hybridization; D005260:Female; D017353:Gene Deletion; D057895:Haploinsufficiency; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000175:diagnosis / Q000235:genetics*; D008297:Male; D055755:SOXD Transcription Factors / Q000235:genetics*
chemical_list: C490301:SOX5 protein, human; D055755:SOXD Transcription Factors