A recurrent 15q13.3 microdeletion syndrome associated with mental retardation and seizures

被引：430

作者：

Sharp, Andrew J. ^{[1
]}

Mefford, Heather C. ^{[1
]}

Li, Kelly ^{[2
]}

Baker, Carl ^{[1
]}

Skinner, Cindy ^{[3
]}

Stevenson, Roger E. ^{[3
]}

Schroer, Richard J. ^{[3
]}

Novara, Francesca ^{[4
]}

De Gregori, Manuela ^{[4
]}

Ciccone, Roberto ^{[4
]}

Broomer, Adam ^{[2
]}

Casuga, Iris ^{[2
]}

Wang, Yu ^{[2
]}

Xiao, Chunlin ^{[2
]}

Barbacioru, Catalin ^{[2
]}

Gimelli, Giorgio ^{[5
]}

Bernardina, Bernardo Dalla ^{[6
]}

Torniero, Claudia ^{[6
]}

Giorda, Roberto ^{[7
]}

Regan, Regina ^{[8
]}

Murday, Victoria ^{[9
]}

Mansour, Sahar ^{[10
]}

Fichera, Marco ^{[11
]}

Castiglia, Lucia ^{[11
]}

Failla, Pinella ^{[11
]}

Ventura, Mario ^{[12
]}

Jiang, Zhaoshi ^{[1
]}

Cooper, Gregory M. ^{[1
]}

Knight, Samantha J. L. ^{[8
]}

Romano, Corrado ^{[11
]}

Zuffardi, Orsetta ^{[4
,13
]}

Chen, Caifu ^{[2
]}

Schwartz, Charles E. ^{[3
]}

Eichler, Evan E. ^{[1
,14
]}

机构：

[1] Univ Washington, Sch Med, Dept Genome Sci, Seattle, WA 98195 USA

[2] Appl Biosyst Inc, Assays Arrays R&D, Foster City, CA 94404 USA

[3] Greenwood Genet Ctr, JC Self Res Inst, Greenwood, SC 29646 USA

[4] Univ Pavia, I-27100 Pavia, Italy

[5] Ist Giannina Gaslini, I-16147 Genoa, Italy

[6] Univ Verona, Policlin GB Rossi, Servizio Neuropsichiatr Infantile, I-37134 Verona, Italy

[7] IRCCS E Medea, I-23842 Bosisio Parini, Italy

[8] Churchill Hosp, Wellcome Trust Ctr Human Genet, Oxford Natl Inst Hlth Res NIHR Biomed Res Ctr, Oxford OX3 7BN, England

[9] Duncan Guthrie Inst Med Genet, Dept Med Genet, Glasgow G3 8SJ, Lanark, Scotland

[10] St George Hosp, SW Reg Genet Serv, London SW17 0RE, England

[11] IRCCS, Assoc Oasi Maria Santissima, I-94018 Troina, Italy

[12] Univ Bari, Dipartimento Genet & Microbiol, I-27100 Pavia, Italy

[13] Fdn IRCCS Policlin San Matteo, I-27100 Pavia, Italy

[14] Howard Hughes Med Inst, Seattle, WA 98195 USA

来源：

NATURE GENETICS | 2008年 / 40卷 / 03期

关键词：

D O I：

10.1038/ng.93

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

We report a recurrent microdeletion syndrome causing mental retardation, epilepsy and variable facial and digital dysmorphisms. We describe nine affected individuals, including six probands: two with de novo deletions, two who inherited the deletion from an affected parent and two with unknown inheritance. The proximal breakpoint of the largest deletion is contiguous with breakpoint 3 (BP3) of the Prader-Willi and Angelman syndrome region, extending 3.95 Mb distally to BP5. A smaller 1.5-Mb deletion has a proximal breakpoint within the larger deletion (BP4) and shares the same distal BP5. This recurrent 1.5-Mb deletion contains six genes, including a candidate gene for epilepsy (CHRNA7) that is probably responsible for the observed seizure phenotype. The BP4-BP5 region undergoes frequent inversion, suggesting a possible link between this inversion polymorphism and recurrent deletion. The frequency of these microdeletions in mental retardation cases is similar to 0.3% (6/2,082 tested), a prevalence comparable to that of Williams, Angelman and Prader-Willi syndromes.

引用

页码：322 / 328

页数：7

共 31 条

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