Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome

Maria Clara Bonaglia, R. Giorda, E. Mani, G. Aceti, B. M. Anderlid, A. Baroncini, T. Pramparo, O. Zuffardi

Research output: Contribution to journalArticle

Abstract

Introduction: The 22q13.3 deletion syndrome (MIM 606232) is characterised by neonatal hypotonia, normal to accelerated growth, absent to severely delayed speech, global developmental delay, and minor dysmorphic facial features. We report the molecular characterisation of the deletion breakpoint in two unrelated chromosome 22q13.3 deletion cases. Methods: The deletions were characterised by FISH, checked for other abnormalities by array-CGH, and confirmed by Real-Time PCR, and finally the breakpoints were cloned, sequenced, and compared. Results: Both cases show the cardinal features of the 22q13.3 deletion syndrome associated with a deletion involving the last 100kb of chromosome 22q13.3. The cases show a breakpoint within the same 15 bp repeat unit, overlapping the results obtained by Wong and colleagues in 1997 and suggesting that a recurrent deletion breakpoint exists within the SHANK3 gene. The direct repeat involved in these 22q13 deletion cases is presumably able to form slipped (hairpin) structures, but it also has a strong potential for forming tetraplex structures. Discussion: Three cases with a common breakpoint within SHANK3 share a number of common phenotypic features, such as mental retardation and developmental delay with severely delayed or absent expressive speech. The two cases presented here, having a deletion partially overlapping the commercial subtelomeric probe, highlight the difficulties in interpreting FISH results and suggest that many similar cases may be overlooked.

Original languageEnglish
Pages (from-to)822-828
Number of pages7
JournalJournal of Medical Genetics
Volume43
Issue number10
DOIs
Publication statusPublished - Oct 2006

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

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