A case of autism and uniparental disomy of chromosome 1.
We report a male child with autism found to have maternal uniparental disomy (UPD) of chromosome 1. The child met diagnostic criteria for the three symptom domains of autism: language impairment, deficient social communication and excessively rigid and repetitive behaviours. He also had a variety of features often associated with autism, including mild mental retardation, small head circumference, hyperactivity, poor fine motor skills, slightly dysmorphic facial features and a heightened interest in olfactory stimulation. His brother, who did not have chromosome 1 UPD, was also autistic. The mother, but not the father, had a history of psychiatric illness and a number of personality and social traits similar to the core features of autism. The discovery of the cytogenetic abnormality was made during the course of a genome-wide linkage screen, wherein genotypes at 6 out of 17 chromosome 1 markers were non-Mendelian and all transmissions were consistent with UPD. Further genotyping (a total of 54 markers) revealed alternating regions of heterodisomy and isodisomy. Whereas chromosome 1 UPD has not been shown to cause disease by effects on imprinting, numerous reports exist of the abnormality unmasking recessive disease-causing mutations. In agreement with this, one of the regions of isodisomy overlaps an emerging chromosome 1 region of interest in autism located at 150-160 Mb.
Wassink
Thomas H
TH
Department of Psychiatry, Carver College of Medicine, University of Iowa, Iowa City, IA 52242, USA. thomas-wassink@uiowa.edu
Losh
Molly
M
Frantz
Rebecca S
RS
Vieland
Veronica J
VJ
Goedken
Rhinda
R
Piven
Joseph
J
Sheffield
Val C
VC
D001321:Autistic Disorder / Q000235:genetics* / Q000473:pathology; D002675:Child, Preschool; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D005260:Female; D005819:Genetic Markers / Q000235:genetics; D006801:Humans; D008297:Male; D009154:Mutation; D010375:Pedigree; D024182:Uniparental Disomy / Q000235:genetics* / Q000473:pathology
D005819:Genetic Markers