Array CGH identifies reciprocal 16p13.1 duplications and deletions that predispose to autism and/or mental retardation.
Autism and mental retardation (MR) are often associated, suggesting that these conditions are etiologically related. Recently, array-based comparative genomic hybridization (array CGH) has identified submicroscopic deletions and duplications as a common cause of MR, prompting us to search for such genomic imbalances in autism. Here we describe a 1.5-Mb duplication on chromosome 16p13.1 that was found by high-resolution array CGH in four severe autistic male patients from three unrelated families. The same duplication was identified in several variably affected and unaffected relatives. A deletion of the same interval was detected in three unrelated patients with MR and other clinical abnormalities. In one patient we revealed a further rearrangement of the 16p13 imbalance that was not present in his unaffected mother. Duplications and deletions of this 1.5-Mb interval have not been described as copy number variants in the Database of Genomic Variants and have not been identified in >600 individuals from other cohorts examined by high-resolution array CGH in our laboratory. Thus we conclude that these aberrations represent recurrent genomic imbalances which predispose to autism and/or MR.
Ullmann
Reinhard
R
Max Planck Institute for Molecular Genetics, Berlin, Germany. ullmann@molgen.mpg.de
Turner
Gillian
G
Kirchhoff
Maria
M
Chen
Wei
W
Tonge
Bruce
B
Rosenberg
Carla
C
Field
Michael
M
Vianna-Morgante
Angela M
AM
Christie
Louise
L
Krepischi-Santos
Ana C
AC
Banna
Lynn
L
Brereton
Avril V
AV
Hill
Alyssa
A
Bisgaard
Anne-Marie
AM
Müller
Ines
I
Hultschig
Claus
C
Erdogan
Fikret
F
Wieczorek
Georg
G
Ropers
H Hilger
HH
D001321:Autistic Disorder / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002885:Chromosomes, Human, Pair 16; D015331:Cohort Studies; D005260:Female; D020440:Gene Duplication; D020022:Genetic Predisposition to Disease; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009693:Nucleic Acid Hybridization / Q000379:methods*; D010375:Pedigree; D016133:Polymerase Chain Reaction