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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
- Source :
- Human Mutation, vol. 33, no. 1, pp. 165-179
- Publication Year :
- 2012
-
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.
- Subjects :
- Male
Ataxia
DNA Copy Number Variations
Developmental Disabilities
Vesicular Acetylcholine Transport Proteins
Non-allelic homologous recombination
Penetrance
Biology
Article
Abnormalities, Multiple/genetics
Child
Child, Preschool
Chromosome Aberrations
Chromosome Mapping
Chromosomes, Human, Pair 10
Developmental Disabilities/complications
Developmental Disabilities/genetics
Female
Genetic Variation
Homologous Recombination
Humans
In Situ Hybridization, Fluorescence
Infant
Intellectual Disability/complications
Intellectual Disability/genetics
Nerve Growth Factors/genetics
Oligonucleotide Array Sequence Analysis
Segmental Duplications, Genomic/genetics
Sequence Deletion
Vesicular Acetylcholine Transport Proteins/genetics
Segmental Duplications, Genomic
Intellectual Disability
Genetics
medicine
Abnormalities, Multiple
Nerve Growth Factors
Expressivity (genetics)
Gene
Genetics (clinical)
Segmental duplication
Low copy repeats
Hypotonia
medicine.symptom
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Human Mutation, vol. 33, no. 1, pp. 165-179
- Accession number :
- edsair.doi.dedup.....e7c5ff84f9bf9a002bde387a5c6e38cf