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Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.


ABSTRACT: We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplications have additional copy number changes. Detailed clinical evaluation of 20 patients with deletions revealed variable clinical features, with developmental delay (DD) and/or intellectual disability (ID) as the only features common to a majority of individuals. We suggest that some of the other features present in more than one patient with deletion, including hypotonia, sleep apnea, chronic constipation, gastroesophageal and vesicoureteral refluxes, epilepsy, ataxia, dysphagia, nystagmus, and ptosis may result from deletion of the CHAT gene, encoding choline acetyltransferase, and the SLC18A3 gene, mapping in the first intron of CHAT and encoding vesicular acetylcholine transporter. The phenotypic diversity and presence of the deletion in apparently normal carrier parents suggest that subjects carrying 10q11.21q11.23 deletions may exhibit variable phenotypic expressivity and incomplete penetrance influenced by additional genetic and nongenetic modifiers.

SUBMITTER: Stankiewicz P 

PROVIDER: S-EPMC3655525 | biostudies-literature | 2012 Jan

REPOSITORIES: biostudies-literature

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Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.

Stankiewicz Paweł P   Kulkarni Shashikant S   Dharmadhikari Avinash V AV   Sampath Srirangan S   Bhatt Samarth S SS   Shaikh Tamim H TH   Xia Zhilian Z   Pursley Amber N AN   Cooper M Lance ML   Shinawi Marwan M   Paciorkowski Alex R AR   Grange Dorothy K DK   Noetzel Michael J MJ   Saunders Scott S   Simons Paul P   Summar Marshall M   Lee Brendan B   Scaglia Fernando F   Fellmann Florence F   Martinet Danielle D   Beckmann Jacques S JS   Asamoah Alexander A   Platky Kathryn K   Sparks Susan S   Martin Ann S AS   Madan-Khetarpal Suneeta S   Hoover Jacqueline J   Medne Livija L   Bonnemann Carsten G CG   Moeschler John B JB   Vallee Stephanie E SE   Parikh Sumit S   Irwin Polly P   Dalzell Victoria P VP   Smith Wendy E WE   Banks Valerie C VC   Flannery David B DB   Lovell Carolyn M CM   Bellus Gary A GA   Golden-Grant Kathryn K   Gorski Jerome L JL   Kussmann Jennifer L JL   McGregor Tracy L TL   Hamid Rizwan R   Pfotenhauer Jean J   Ballif Blake C BC   Shaw Chad A CA   Kang Sung-Hae L SH   Bacino Carlos A CA   Patel Ankita A   Rosenfeld Jill A JA   Cheung Sau Wai SW   Shaffer Lisa G LG  

Human mutation 20111102 1


We report 24 unrelated individuals with deletions and 17 additional cases with duplications at 10q11.21q21.1 identified by chromosomal microarray analysis. The rearrangements range in size from 0.3 to 12 Mb. Nineteen of the deletions and eight duplications are flanked by large, directly oriented segmental duplications of >98% sequence identity, suggesting that nonallelic homologous recombination (NAHR) caused these genomic rearrangements. Nine individuals with deletions and five with duplication  ...[more]

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