12q21 Interstitial Deletions: Seven New Syndromic Cases Detected by Array-CGH and Review of the Literature

Genes (Basel). 2022 Apr 27;13(5):780. doi: 10.3390/genes13050780.


Interstitial deletions of the long arm of chromosome 12 are rare, with a dozen patients carrying a deletion in 12q21 being reported. Recently a critical region (CR) has been delimited and could be responsible for the more commonly described clinical features, such as developmental delay/intellectual disability, congenital genitourinary and brain malformations. Other, less frequent, clinical signs do not seem to be correlated to the proposed CR. We present seven new patients harboring non-recurrent deletions ranging from 1 to 18.5 Mb differentially scattered across 12q21. Alongside more common clinical signs, some patients have rarer features such as heart defects, hearing loss, hypotonia and dysmorphisms. The correlation of haploinsufficiency of genes outside the CR to specific signs contributes to our knowledge of the effect of the deletion of this gene-poor region of chromosome 12q. This work underlines the still important role of copy number variations in the diagnostic setting of syndromic patients and the positive reflection on management and family genetic counseling.

Keywords: 12q21 deletion; array-CGH; congenital anomalies; copy number variants (CNVs); developmental delay/intellectual disability (DD/ID); dysmorphisms; genetic counseling; loss of function; patient management; variation intolerant genes.

Publication types

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

MeSH terms

  • Chromosome Deletion*
  • Chromosome Structures
  • Comparative Genomic Hybridization
  • DNA Copy Number Variations / genetics
  • Humans
  • Intellectual Disability* / genetics

Grants and funding

This work was partially supported by the Italian Ministry of Health funding to IRCCS Istituto Auxologico Italiano (RC 08C923 2019).