Autistic disorder phenotype associated to a complex 15q intrachromosomal rearrangement.
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.
Genetics Division, Department of Gynecology and Obstetrics, Faculdade de Medicina do ABC (1) (FMABC), São Paulo, Brazil. denise.morf@gmail.com
Denise Maria
DM
Christofolini
Vera Ayres
VA
Meloni
Marco Antonio de Paula
MA
Ramos
Mariana Moysés
MM
Oliveira
Claudia Berlim
CB
de Mello
Renata
R
Pellegrino
Sylvia Satomi
SS
Takeno
Maria Isabel
MI
Melaragno
D000293:Adolescent; D001321:Autistic Disorder / Q000235:genetics; D002869:Chromosome Aberrations; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability; D008297:Male; D010641:Phenotype