An 800 kb deletion at 17q23.2 including the MED13 (THRAP1) gene, revealed by aCGH in a patient with a SMC 17p

Am J Med Genet A. 2012 Feb;158A(2):400-5. doi: 10.1002/ajmg.a.34222. Epub 2011 Dec 7.

Abstract

We report on clinical and cytogenetic studies in a 7-year-old child with moderate intellectual disability, short stature, mild dysmorphism, and hearing loss. R-chromosome banding showed a de novo autosomal marker originating from the 17p chromosome segment in all cells analyzed. Array comparative genome hybridization (aCGH) was used to determine the gene content and proximal and distal breakpoints of the small supernumerary marker chromosome (SMC). These breakpoints mapped to the centromere of chromosome 17 and the 17p11.2 region, respectively. Unexpectedly, aCGH analysis also revealed a de novo deletion of 800 kb encompassing six genes in the 17q23.2 region, including MED13 (also known as THRAP1). We compared our patient with other reported cases of SMC(17), to determine the respective contributions of the duplication and the deletion to the phenotype. We cannot entirely exclude a minor role for the SMC(17), but we suggest that MED13 haploinsufficiency was responsible for the phenotype of the patient particularly the cataract, hearing loss and semicircular canal dysplasia. Moreover, this report highlights the usefulness of aCGH for the specification of gene content in cases of abnormality, facilitating the establishment of accurate phenotype-genotype correlations and the detection of other, complex rearrangements.

Publication types

  • Case Reports

MeSH terms

  • Body Dysmorphic Disorders / diagnosis
  • Body Dysmorphic Disorders / genetics
  • Body Dysmorphic Disorders / pathology
  • Child
  • Chromosome Breakpoints
  • Chromosome Deletion*
  • Chromosome Disorders / diagnosis
  • Chromosome Disorders / genetics*
  • Chromosome Disorders / pathology*
  • Chromosomes, Human, Pair 17 / genetics*
  • Comparative Genomic Hybridization
  • Haploinsufficiency / genetics
  • Hearing Loss / diagnosis
  • Hearing Loss / genetics
  • Hearing Loss / pathology
  • Humans
  • Intellectual Disability / diagnosis
  • Intellectual Disability / genetics
  • Intellectual Disability / pathology
  • Mediator Complex / genetics*

Substances

  • MED13 protein, human
  • Mediator Complex