Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes

Bruno, Damien L., Anderlid, Britt-Marie, Lindstrand, Anna, Van Ravenswaaij-Arts, Conny, Ganesamoorthy, Devika, Lundin, Johanna, Martin, Christa Lese, Douglas, Jessica, Nowak, Catherine, Adam, Margaret P., Kooy, R. Frank, Van Der Aa, Nathalie, Reyniers, Edwin, Vandeweyer, Geert, Stolte-Dijkstra, Irene, Dijkhuizen, Trijnie, Yeung, Alison, Delatycki, Martin, Borgstrom, Birgit, Thelin, Lena, Cardoso, Carlos, Van Bon, Bregje, Pfundt, Rolph, De Vries, Bert B. A., Wallin, Anders, Amor, David J., James, Paul A., Slater, Howard R. and Schoumans, Jacqueline (2010) Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes. Journal of Medical Genetics, 47 5: 299-311. doi:10.1136/jmg.2009.069906

Author Bruno, Damien L.
Anderlid, Britt-Marie
Lindstrand, Anna
Van Ravenswaaij-Arts, Conny
Ganesamoorthy, Devika
Lundin, Johanna
Martin, Christa Lese
Douglas, Jessica
Nowak, Catherine
Adam, Margaret P.
Kooy, R. Frank
Van Der Aa, Nathalie
Reyniers, Edwin
Vandeweyer, Geert
Stolte-Dijkstra, Irene
Dijkhuizen, Trijnie
Yeung, Alison
Delatycki, Martin
Borgstrom, Birgit
Thelin, Lena
Cardoso, Carlos
Van Bon, Bregje
Pfundt, Rolph
De Vries, Bert B. A.
Wallin, Anders
Amor, David J.
James, Paul A.
Slater, Howard R.
Schoumans, Jacqueline
Title Further molecular and clinical delineation of co-locating 17p13.3 microdeletions and microduplications that show distinctive phenotypes
Journal name Journal of Medical Genetics   Check publisher's open access policy
ISSN 0022-2593
Publication date 2010-05-01
Year available 2010
Sub-type Article (original research)
DOI 10.1136/jmg.2009.069906
Open Access Status Not Open Access
Volume 47
Issue 5
Start page 299
End page 311
Total pages 13
Place of publication London, United Kingdom
Publisher BMJ Group
Language eng
Formatted abstract
Background Chromosome 17p13.3 contains extensive repetitive sequences and is a recognised region of genomic instability. Haploinsufficiency of PAFAH1B1 (encoding LIS1) causes either isolated lissencephaly sequence or Miller–Dieker syndrome, depending on the size of the deletion. More recently, both microdeletions and microduplications mapping to the Miller–Dieker syndrome telomeric critical region have been identified and associated with distinct but overlapping phenotypes.
Methods Genome-wide microarray screening was performed on 7678 patients referred with unexplained learning difficulties and/or autism, with or without other congenital abnormalities. Eight and five unrelated individuals, respectively, were identified with microdeletions and microduplications in 17p13.3.
Results Comparisons with six previously reported microdeletion cases identified a 258 kb critical region, encompassing six genes including CRK (encoding Crk) and YWHAE (encoding 14-3-3ε). Clinical features included growth retardation, facial dysmorphism and developmental delay. Notably, one individual with only subtle facial features and an interstitial deletion involving CRK but not YWHAE suggested that a genomic region spanning 109 kb, encompassing two genes (TUSC5 and YWHAE), is responsible for the main facial dysmorphism phenotype. Only the microduplication phenotype included autism. The microduplication minimal region of overlap for the new and previously reported cases spans 72 kb encompassing a single gene, YWHAE. These genomic rearrangements were not associated with low-copy repeats and are probably due to diverse molecular mechanisms.
Conclusions The authors further characterise the 17p13.3 microdeletion and microduplication phenotypic spectrum and describe a smaller critical genomic region allowing identification of candidate genes for the distinctive facial dysmorphism (microdeletions) and autism (microduplications) manifestations.
Keyword Genetics & Heredity
Genetics & Heredity
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: Institute for Molecular Bioscience - Publications
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