Identification of a recurrent breakpoint within the SHANK3 gene in the 22q13.3 deletion syndrome
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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.
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Loss of a functional copy of the SHANK3 gene leads to the neurobehavioral manifestations of 22q13 deletion syndrome and/or to autism spectrum disorders.
“Loss of a functional copy of the SHANK3 gene leads to the neurobehavioral manifestations of 22q13 deletion syndrome and/or to autism spectrum disorders.”
From Haploinsufficiency of the autism-associated Shank3 gene leads to deficits in synaptic function, social interaction, and social communication (2010) · cites this paper as [24]
Features of Angelman, Phelan McDermid, and Smith-Magenis syndromes can be recapitulated by point mutations in UBE3A, SHANK3, and RAI1 respectively.
“For example, clinical features of Angelman, Phelan McDermid and Smith-Magenis Syndromes, which are caused by large deletions of multiple genes, can be recapitulated by point mutations in UBE3A (Fang et al., 1999) and SHANK3 (Bonaglia et al., 2006) and RAI1 (Slager et al., 2003) respectively.”
From Getting to the cores of autism (2019) · cites this paper as Bonaglia et al., 2006
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- Authors
- Bonaglia, M. C., Giorda, R., Mani, E., Aceti, G., Anderlid, B.-M., Baroncini, A., Pramparo, T., & Zuffardi, O.
- Affiliations
- IRCCS Eugenio Medea (IT)
- Karolinska University Hospital (SE)
- University of Pavia (IT)
- Corresponding author
- Bonaglia, M C
- Venue
- Journal of Medical Genetics
- Publisher
- BMJ
- Published
- 2005-11-11
- Volume
- 43
- Issue
- 10
- Pages
- 822-828
- ISSN
- 0022-2593 (ISSN-L)
- 1468-6244
- PMC
- PMC2563164
- OpenAlex
- W2135686500
- Cited by
- 211
- References
- 31
- Citations by year
- 2025: 4 · 2024: 3 · 2023: 7 · 2022: 10 · 2021: 11 · 2020: 2 · 2019: 4 · 2018: 8 · 2017: 9 · 2016: 6 · 2015: 8 · 2014: 12 · 2013: 15 · 2012: 17
- FWCI
- 3.42
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Medical Genetics (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Fondazione Cariplo
- Ministero dell’Istruzione, dell’Università e della Ricerca (FIRB_2001)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomic variations and chromosomal abnormalities
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- SHANK3, direct repeats, developmental delay, intellectual disability, fish
- MeSH terms
- Abnormalities, Multiple, Adolescent, Base Sequence, Carrier Proteins, Chromosome Deletion, Chromosomes, Human, Pair 22, Female, Humans, Intellectual Disability, Molecular Sequence Data, Nerve Tissue Proteins, Recurrence, Sequence Homology, Nucleic Acid, Syndrome, In Situ Hybridization, Fluorescence, Chromosome Breakage
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