Table 2.
Rare exome findings in the study sample.
|
Pedigree |
Gene | Description | Variant | dbSNP ID | Consequences | AF | Associated phenotype | Impact |
|---|---|---|---|---|---|---|---|---|
| f-CeAD | ||||||||
| 2 | MEF2A | Myocyte enhancer factor 2A | Pro279Leu | rs121918529 | Pathogenic | 0.0012 | Coronary artery disease, AD, 1 | Suggestive |
| 3 | COL3A1 | Collagen type III α1 chain | Gly324Ser | Unknown | Pathogenic | <0.0001 | EDS, type 4 | Disease-causing |
| 4 | MEF2A | Myocyte enhancer factor 2A | Pro279Leu | rs121918529 | Pathogenic | 0.0012 | Coronary artery disease, AD, 1 | Suggestive |
| 5 | FBN1 | Fibrillin 1 | Arg2544Trp | rs369294972 | Pathogenic | <0.0001 | Marfan syndrome | Disease-causing |
| 6 | COL4A1 | Collagen type IV α1 chain | Pro116Leu | rs538816765 | Pathogenic | <0.0001 | HANAC syndrome | Disease-causing |
| 13 | COL5A1 COL5A1 | Collagen type V α1 chain Collagen type V α1 chain | Arg65Trp Val172Phe | rs139468527 rs150147262 | Pathogenic VUS | 0.00190.0006 | EDS, classic type, 1 EDS, classic type, 1 | Disease-causing |
| 14 | COL4A3 COL4A4 | Collagen type IV α3 chain Collagen type IV α4 chain | Leu1474Pro Gly972Arg | rs200302125 rs767704202 | Pathogenic Pathogenic | 0.0046 <0.0001 | Alport syndrome, ar | Disease-causing |
| 16 | COL5A2 COL5A1 | Collagen type V α2 chain Collagen type V α1 chain | Pro1103Leu Thr1757Met | rs150401168 rs2229817 | VUSVUS | <0.00010.0019 | EDS, classic type, 2EDS, classic type, 1 | Suggestive |
| r-CeAD | ||||||||
| 19 | COL3A1 | Collagen type III α1 chain | Lys1313Arg | rs111840783 | VUS | 0.0013 | EDS, type 4 | Suggestive |
| 23 | ABCC6 | ATP binding cassette subfamily C member 6 | Arg1141Stop | rs72653706 | Pathogenic | 0.0021 | Arterial calcification of infancy, 2 | Suggestive |
| 26 | COL5A2 | Collagen type V α2 chain | Gly213Ser | rs753789459 | Pathogenic | <0.0001 | EDS, classic type, 2 | Suggestive |
| 27 | RNF213 | Ring finger protein 213 | Trp1231Leu | rs61741961 | Pathogenic | 0.0151 | Moyamoya disease 2, susceptibility to | Suggestive |
| 28 | RNF213 | Ring finger protein 213 | His1231Asp | not in dbSNP | Pathogenic | <0.0001 | Moyamoya disease 2, susceptibility to | Suggestive |
| 32 | ABCC6 | ATP binding cassette subfamily C member 6 | Arg1141Stop | rs72653706 | Pathogenic | 0.0021 | Arterial calcification of infancy, 2 | Suggestive |
Note: Variants were considered pathogenic if assigned ‘pathogenic’ in the ClinVar database or if pathogenicity was predicted by Polyphen-2 as well as by SIFT. The allele frequency of the variants was assessed for the European (non-Finnish) population of the ExAC database. Associated phenotypes were found in the OMIM database. Pathogenic findings in genes associated with arterial aneurysm or dissection were considered as ‘disease-causing’. Variants of unknown significance (VUS) in genes associated with arterial aneurysm or dissection and pathogenic variants in genes associated with other vascular conditions were considered as ‘suggestive’.
AF: allele frequency; EDS: Ehlers–Danlos syndrome; HANAC: hereditary angiopathy with nephropathy, aneurysms, and muscle cramps.