5q11.2 deletion syndrome revisited-Further narrowing of the smallest region of overlap for the main clinical characteristics of the syndrome

Am J Med Genet A. 2021 Dec;185(12):3844-3850. doi: 10.1002/ajmg.a.62428. Epub 2021 Jul 28.

Abstract

Microdeletions at 5q11.2 are rare. Subjects show a phenotypic spectrum that overlaps CHARGE syndrome and 22q11.2 deletion syndrome. A growing number of subjects present with learning difficulty and/or intellectual disability, immune deficiency, congenital heart malformation, and dysmorphism. DHX29 and IL6ST have been proposed as candidate genes for the development of the major clinical manifestations. We present a new case and narrow down the shortest region of overlap to evaluate possible candidate genes. Our case does not present developmental delay or immune deficiency indicating a reduced penetrance for some of the main clinical manifestations. The shortest region of overlap between subjects with deletions at 5q11.2 is approximately 450 kb (position 54.3-54.7 Mb). The narrowed region comprises 10 protein coding genes, including DHX29. DHX29 is a strong candidate gene for the main features of 5q11.2-microdeletion syndrome; however, our findings suggest a joined impact of several genes as the cause of the syndrome.

Keywords: 5q11.2 microdeletion syndrome; DHX29; developmental delay; immunodeficiency; shortest region of overlap.

Publication types

  • Case Reports
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Abnormalities, Multiple / genetics*
  • Abnormalities, Multiple / physiopathology
  • Anemia, Macrocytic / genetics*
  • Anemia, Macrocytic / physiopathology
  • Child, Preschool
  • Chromosome Deletion
  • Chromosomes, Human, Pair 5 / genetics
  • Comparative Genomic Hybridization
  • Cytokine Receptor gp130 / genetics
  • Developmental Disabilities / genetics
  • Developmental Disabilities / physiopathology
  • Facies
  • Heart Defects, Congenital / genetics*
  • Heart Defects, Congenital / physiopathology
  • Humans
  • Infant
  • Infant, Newborn
  • Intellectual Disability / genetics*
  • Intellectual Disability / physiopathology
  • Learning Disabilities / genetics
  • Learning Disabilities / physiopathology
  • Male
  • Phenotype
  • RNA Helicases / genetics*

Substances

  • IL6ST protein, human
  • Cytokine Receptor gp130
  • DHX29 protein, human
  • RNA Helicases

Supplementary concepts

  • Chromosome 5q Deletion Syndrome