Recurrent deletions and reciprocal duplications of 10q11.21q11.23 including CHAT and SLC18A3 are likely mediated by complex low-copy repeats.
Hum Mutat
; 33(1): 165-79, 2012 Jan.
Article
in En
| MEDLINE
| ID: mdl-21948486
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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Abnormalities, Multiple
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Chromosome Aberrations
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Sequence Deletion
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Vesicular Acetylcholine Transport Proteins
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Segmental Duplications, Genomic
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Nerve Growth Factors
Type of study:
Prognostic_studies
Limits:
Child
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Child, preschool
/
Female
/
Humans
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Infant
/
Male
Language:
En
Journal:
Hum Mutat
Journal subject:
GENETICA MEDICA
Year:
2012
Type:
Article
Affiliation country:
United States