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 100 kb 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.
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 100 kb 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.
Authors: Heidi A Heilstedt; Blake C Ballif; Leslie A Howard; Richard A Lewis; Samuel Stal; Catherine D Kashork; Carlos A Bacino; Stuart K Shapira; Lisa G Shaffer Journal: Am J Hum Genet Date: 2003-04-08 Impact factor: 11.025
Authors: M C Bonaglia; R Giorda; R Borgatti; G Felisari; C Gagliardi; A Selicorni; O Zuffardi Journal: Am J Hum Genet Date: 2001-06-18 Impact factor: 11.025
Authors: M C Phelan; R C Rogers; R A Saul; G A Stapleton; K Sweet; H McDermid; S R Shaw; J Claytor; J Willis; D P Kelly Journal: Am J Med Genet Date: 2001-06-15
Authors: Lionel Willatt; James Cox; John Barber; Elisabet Dachs Cabanas; Amanda Collins; Dian Donnai; David R FitzPatrick; Eddy Maher; Howard Martin; Josep Parnau; Lesley Pindar; Jacqueline Ramsay; Charles Shaw-Smith; Erik A Sistermans; Michael Tettenborn; Dorothy Trump; Bert B A de Vries; Kate Walker; F Lucy Raymond Journal: Am J Hum Genet Date: 2005-05-25 Impact factor: 11.025
Authors: Svetlana A Yatsenko; Ellen K Brundage; Erin K Roney; Sau Wai Cheung; A Craig Chinault; James R Lupski Journal: Hum Mol Genet Date: 2009-03-17 Impact factor: 6.150
Authors: Mehreen Kouser; Haley E Speed; Colleen M Dewey; Jeremy M Reimers; Allie J Widman; Natasha Gupta; Shunan Liu; Thomas C Jaramillo; Muhammad Bangash; Bo Xiao; Paul F Worley; Craig M Powell Journal: J Neurosci Date: 2013-11-20 Impact factor: 6.167