Table 2.
COL5A1 and COL5A2 mutations in patients with cEDS
| Patient(s) IDs | Gene | Exon, intron/localization | a Change at the nucleotide level | b Nonsense/Missense | b Frameshift | Splice site |
|---|---|---|---|---|---|---|
|
Mutations leading to type V collagen haploinsufficiency | ||||||
|
AN_002501 |
A1 |
ex1/N-propeptide |
c.87G>A° |
p.(Trp29*) |
|
|
|
AN_002503-05# |
A1 |
int7/N-propeptide |
c.1165-2A>G |
|
p.(Pro389Leufs*168) |
c Activation of cryptic splice acceptor site 4 bp downstream of WT acceptor |
|
AN_002506 |
A1 |
ex13/N-propeptide |
c.1651C>T° |
p.(Gln551*) |
|
|
|
AN_002509 |
A1 |
int31/helix |
c.2647-12A>G° |
|
p.(Gly883Leufs*195) |
c Creation of new splice acceptor site 11 bp upstream of WT acceptor |
|
AN_002510 |
A1 |
ex34/helix |
c.2757_2774del18insA° |
|
p.(Glu920Hisfs*14) |
|
|
AN_002511 |
A1 |
ex36/helix |
c.2891dup° |
|
p.(Gly967Trpfs*47) |
|
|
AN_002514-15* |
A1 |
ex38/helix |
c.2988del° |
|
p.(Gly997Alafs*77) |
|
|
AN_002516 |
A1 |
ex38/helix |
c.2988dup^ e |
|
p.(Gly997Argfs*17) |
|
|
AN_002517 |
A1 |
ex42/helix |
c.3328C>T° |
p.(Gln1110*) |
|
|
|
AN_002520-23# |
A1 |
ex45/helix |
c.3568C>T |
p.(Gln1190*) |
|
|
|
AN_002524-25* |
A1 |
ex48/helix |
c.3769C>T° e |
p.(Arg1257*) |
|
|
|
AN_002527 |
A1 |
ex62/C-propeptide |
c.4714del° |
|
p.(Val1572Serfs*47) |
|
|
AN_002528-29# |
A1 |
ex62/C-propeptide |
c.4919_4928del10^ |
|
p.(Lys1640Serfs*86) |
|
|
AN_002530-31# |
A1 |
ex63/C-propeptide |
c.4962C>G |
p.(Tyr1654*) |
|
|
|
AN_002532 |
A1 |
ex66/C-propeptide |
c.5458_5459del° |
|
p.(Phe1820Argfs*2) |
|
|
Large genomic rearrangement identified by MLPA and SNP-array | ||||||
|
AN_002535-37# |
A1 |
|
chr9.hg19:g.(137,440,166_137,442,686)_(137,633,699_137,638,368)dup |
|||
|
Mutations affecting the structural integrity of type V collagen | ||||||
|
AN_002502 |
A1 |
ex4/N-propeptide |
c.532A>C° |
p.(Thr178Pro) |
|
|
|
AN_002507-08# |
A1 |
ex29/helix |
c.2436A>T |
p.(Glu812Asp) |
|
c alteration of an ESE sequence, splice error? |
|
AN_002512-13# |
A1 |
int37/helix |
c.2952+2_2952+3del |
p.(Gly967_Thr984del) |
|
c in-frame exon 37 skipping |
|
AN_002518-19# |
A1 |
ex43/helix |
c.3413G>Ae |
p.(Gly1138Glu) |
|
|
|
AN_002526 |
A1 |
ex54/helix |
c.4178G>A° |
p.(Gly1393Asp) |
|
|
|
AN_002533 |
A2 |
ex29/helix |
c.1977G>A° |
p.(Gly642_Pro659del) |
|
c in-frame exon 29 skipping |
| AN_002534 | A2 | int37/helix | c.2499+2T>C° | p.(Gly816_Pro833del) | d in-frame exon 37 skipping | |
The patient(s) IDs correspond to the identifiers found in the LOVD EDS Variant Database (http://www.le.ac.uk/ge/collagen/); a DNA mutation numbering is based on the cDNA sequence. For cDNA numbering, +1 corresponds to the A of the ATG translation initiation codon in the reference sequence. The reference sequences are based on the GenBank Accession no.: COL5A1 NM_000093.3, COL5A2 NM_000393.3. b For protein numbering, +1 corresponds to the first translated amino acid. The reference sequences are based on GenBank Accession no.: COL5A1 NP_000084.3, COL5A2 NP_000384.2. c The effect on splicing was analyzed using four prediction programs (SpliceSite-Finder-like, MaxEntScan, NNSPLICE and Human Splicing Finder) in Alamut software, version 2.2 (Additional file 1: Figures S1–S6). d The effect on mRNA splicing was verified by RT-PCR of total RNA that was purified from the patient’s skin fibroblasts (Additional file 1: Figure S6B). ° de novo mutation verified by parental testing. ^ Parents not available for de novo testing. # Members of the same family. * Members of different families. e Mutation previously reported [18, LOVD].