A polymorphic genomic duplication on human chromosome 15 is a susceptibility factor for panic and phobic disorders.
Anxiety disorders are complex and common psychiatric illnesses associated with considerable morbidity and social cost. We have studied the molecular basis of the cooccurrence of panic and phobic disorders with joint laxity. We have identified an interstitial duplication of human chromosome 15q24-26 (named DUP25), which is significantly associated with panic/agoraphobia/social phobia/joint laxity in families, and with panic disorder in nonfamilial cases. Mosaicism, different forms of DUP25 within the same family, and absence of segregation of 15q24-26 markers with DUP25 and the psychiatric phenotypes suggest a non-Mendelian mechanism of disease-causing mutation. We propose that DUP25, which is present in 7% control subjects, is a susceptibility factor for a clinical phenotype that includes panic and phobic disorders and joint laxity.
Gratacòs
M
M
Centre de Genètica Mèdica i Molecular-IRO, L'Hospitalet de Llobregat, E-08907, Catalonia, Barcelona, Spain.
Nadal
M
M
Martín-Santos
R
R
Pujana
M A
MA
Gago
J
J
Peral
B
B
Armengol
L
L
Ponsa
I
I
Miró
R
R
Bulbena
A
A
Estivill
X
X
D000328:Adult; D000483:Alleles; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D018628:Gene Dosage; D020440:Gene Duplication; D020131:Genes, Duplicate / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D019410:Interleukin-16 / Q000235:genetics; D007593:Joint Instability / Q000150:complications / Q000235:genetics*; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats / Q000235:genetics; D009030:Mosaicism / Q000235:genetics; D009154:Mutation / Q000235:genetics; D016584:Panic Disorder / Q000150:complications / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010698:Phobic Disorders / Q000150:complications / Q000235:genetics*; D020161:Physical Chromosome Mapping; D011110:Polymorphism, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism
D019410:Interleukin-16; D012333:RNA, Messenger