Phenotypic and molecular characterization of 19q12q13.1 deletions: a report of five patients

Am J Med Genet A. 2014 Jan;164A(1):62-9. doi: 10.1002/ajmg.a.36201. Epub 2013 Nov 15.

Abstract

A syndrome associated with 19q13.11 microdeletions has been proposed based on seven previous cases that displayed developmental delay, intellectual disability, speech disturbances, pre- and post-natal growth retardation, microcephaly, ectodermal dysplasia, and genital malformations in males. A 324-kb critical region was previously identified as the smallest region of overlap (SRO) for this syndrome. To further characterize this microdeletion syndrome, we present five patients with deletions within 19q12q13.12 identified using a whole-genome oligonucleotide microarray. Patients 1 and 2 possess deletions overlapping the SRO, and Patients 3-5 have deletions proximal to the SRO. Patients 1 and 2 share significant phenotypic overlap with previously reported cases, providing further definition of the 19q13.11 microdeletion syndrome phenotype, including the first presentation of ectrodactyly in the syndrome. Patients 3-5, whose features include developmental delay, growth retardation, and feeding problems, support the presence of dosage-sensitive genes outside the SRO that may contribute to the abnormal phenotypes observed in this syndrome. Multiple genotype-phenotype correlations outside the SRO are explored, including further validation of the deletion of WTIP as a candidate for male hypospadias observed in this syndrome. We postulate that unique patient-specific deletions within 19q12q13.1 may explain the phenotypic variability observed in this emerging contiguous gene deletion syndrome.

Keywords: 19q12 deletion; 19q13.11 deletion syndrome; aCGH; developmental delay; ectodermal dysplasia; microarray testing; microdeletion.

Publication types

  • Case Reports

MeSH terms

  • Abnormalities, Multiple / genetics
  • Adolescent
  • Child
  • Child, Preschool
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 19*
  • Comparative Genomic Hybridization
  • Facies
  • Female
  • Genetic Diseases, Inborn / diagnosis
  • Genetic Diseases, Inborn / genetics
  • Humans
  • Infant
  • Male
  • Phenotype*
  • Syndrome