Expanding the genotype-phenotype correlation in subtelomeric 19p13.3 microdeletions using high resolution clinical chromosomal microarray analysis

Am J Med Genet A. 2013 Dec;161A(12):2953-63. doi: 10.1002/ajmg.a.35886. Epub 2013 Oct 2.

Abstract

Structural rearrangements of chromosome 19p are rare, and their resulting phenotypic consequences are not well defined. This is the first study to report a cohort of eight patients with subtelomeric 19p13.3 microdeletions, identified using clinical chromosomal microarray analysis (CMA). The deletion sizes ranged from 0.1 to 0.86 Mb. Detailed analysis of the patients' clinical features has enabled us to define a constellation of clinical abnormalities that include growth delay, multiple congenital anomalies, global developmental delay, learning difficulties, and dysmorphic facial features. There are eight genes in the 19p13.3 region that may potentially contribute to the clinical phenotype via haploinsufficiency. Moreover, in silico genomic analysis of 19p13.3 microdeletion breakpoints revealed numerous highly repetitive sequences, suggesting LINEs/SINEs-mediated events in generating these microdeletions. Thus, subtelomeric 19p13.3 appears important for normal embryonic and childhood development. The clinical description of patients with deletions in this genomic interval will assist clinicians to identify and treat individuals with similar deletions.

Keywords: 19p aberrations; 19p13.3 microdeletion; VACTERL; dysmorphic features; genomic microarray; global developmental delay; learning disability; multiple congenital anomalies; subtelomere.

MeSH terms

  • Adult
  • Child
  • Chromosome Breakpoints
  • Chromosome Deletion*
  • Chromosomes, Human, Pair 19 / genetics
  • Developmental Disabilities / genetics*
  • Developmental Disabilities / pathology
  • Female
  • Genetic Association Studies*
  • Humans
  • In Situ Hybridization, Fluorescence
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • Intellectual Disability / pathology
  • Long Interspersed Nucleotide Elements / genetics
  • Male
  • Microarray Analysis
  • Telomere / genetics*