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Autistic disorder phenotype associated to a complex 15q intrachromosomal rearrangement
Author(s) -
Christofolini Denise Maria,
Meloni Vera Ayres,
de Paula Ramos Marco Antonio,
Oliveira Mariana Moysés,
de Mello Claudia Berlim,
Pellegrino Renata,
Takeno Sylvia Satomi,
Melaragno Maria Isabel
Publication year - 2012
Publication title -
american journal of medical genetics part b: neuropsychiatric genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.393
H-Index - 126
eISSN - 1552-485X
pISSN - 1552-4841
DOI - 10.1002/ajmg.b.32089
Subject(s) - gene duplication , multiplex ligation dependent probe amplification , intellectual disability , genetics , chromosomal rearrangement , epilepsy , copy number variation , karyotype , biology , chromosome , neuroscience , gene , exon , genome
Abstract The proximal regions of acrocentric chromosomes, particularly 15q11.2, are frequently involved in structural rearrangement. However, interstitial duplications involving one of the chromosome 15 homologues are less frequent, with few patients described with molecular techniques. These patients present distinctive clinical findings including developmental delay and intellectual disability, minor dysmorphic facial features, epilepsy, and autistic behavior. Here we describe an interstitial rearrangement of chromosome 15 composed of a triplication ∼6.9 Mb from 15q11.2 to 15q13.2 followed by a duplication of ∼2.4 Mb from 15q13.2 to 15q13.3, defined using different approaches as MLPA, qPCR, array and FISH. FISH revealed that the middle part of the triplicated segment was in inverted position. The parental origin of the rearrangement was assessed using methylation assay and SNP array that revealed the maternal origin of the additional material. The patient presents most of the clinical features associated to 15q11.2 triplication: minor dysmorphic facial features, generalized epilepsy, absence seizures, intellectual disability, and autistic behavior. In conclusion, the use of more accurate molecular tools enabled a detailed investigation, providing the identification of intrachromosome duplication/triplication and bringing new light to the study of genetic causes of autistic disorders. © 2012 Wiley Periodicals, Inc.