Aortic dilatation/dissection (AD) can occur spontaneously or in association with 
genetic syndromes, such as Marfan syndrome (MFS; caused by FBN1 mutations), MFS 
type 2 and Loeys-Dietz syndrome (associated with TGFBR1/TGFBR2 mutations), and 
Ehlers-Danlos syndrome (EDS) vascular type (caused by COL3A1 mutations). 
Although mutations in FBN1 and TGFBR1/TGFBR2 account for the majority of AD 
cases referred to us for molecular genetic testing, we have obtained negative 
results for these genes in a large cohort of AD patients, suggesting the 
involvement of additional genes or acquired factors. In this study we assessed 
the effect of COL3A1 deletions/duplications in this cohort. Multiplex 
ligation-dependent probe amplification (MLPA) analysis of 100 unrelated patients 
identified one hemizygous deletion of the entire COL3A1 gene. Subsequent 
microarray analyses and sequencing of breakpoints revealed the deletion size of 
3,408,306 bp at 2q32.1q32.3. This deletion affects not only COL3A1 but also 21 
other known genes (GULP1, DIRC1, COL5A2, WDR75, SLC40A1, ASNSD1, ANKAR, OSGEPL1, 
ORMDL1, LOC100129592, PMS1, MSTN, C2orf88, HIBCH, INPP1, MFSD6, TMEM194B, NAB1, 
GLS, STAT1, and STAT4), mutations in three of which (COL5A2, SLC40A1, and MSTN) 
have also been associated with an autosomal dominant disorder (EDS classical 
type, hemochromatosis type 4, and muscle hypertrophy). Physical and laboratory 
examinations revealed that true haploinsufficiency of COL3A1, COL5A2, and MSTN, 
but not that of SLC40A1, leads to a clinical phenotype. Our data not only 
emphasize the impact/role of COL3A1 in AD patients but also extend the molecular 
etiology of several disorders by providing hitherto unreported evidence for true 
haploinsufficiency of the underlying gene.