ClinGen Dosage Sensitivity Curation Page


  • Curation Status: Complete

Location Information

Select assembly: (NC_000012.11) (NC_000012.12)
Evidence for haploinsufficiency phenotype
PubMed ID Description
22290657 Eight individuals with intragenic SOX5 deletions (four are apparently de novo and one inherited from an affected parent) are described.Common features include prominent speech delay, intellectual disability, behavior abnormalities, and dysmorphic features. The phenotypic impact of the deletions was thought to depend on the location of the deletion within the gene: deletions in UTR regions as opposed to coding regions may not be pathogenic.
23498568 Describes two patients one of whom had an intragenic SOX5 deletion. The de novo deletion was 53Kb and included loss of a protein coding exon of the gene (exon 3, long isoforms, 5'UTR short isoform). Case 1 had diagnoses of moderate intellectual disability, severe expressive language delay, and minor motor impairment.
23220431 Describes three patients with SOX5 deletions. Patient 1 (de novo) and Patient 3 (no parental follow-up available) had deletions that included SOX5 in addition to other genes. Patient 2 had a de novo intragenic SOX5 deletion involving loss of exon 3 (same exon as reference PMID 23498568), sized at approximately 100Kb. Patient had global developmental delay, cognitive impairment and speech delay.

Haploinsufficiency phenotype comments:

SOX5 is the gene responsible for Lamb-Shaffer syndrome, a neurodevelopmental disorder characterized by global developmental delay, intellectual disability, poor expressive speech, and mild dysmorphic facial features (OMIM 616803). Intragenic deletions, loss of function mutations and multi-gene deletions have been described in the medical literature, most of which were de novo. (PMID:22290657; PMID:23498568; PMID:23220431; PMID:26111154).

  • Triplosensitivity score: 0
  • Strength of Evidence (disclaimer): No evidence for dosage pathogenicity