Table 2.
Mutations identified in our cohort.
| Pts | Nucleotide position | Mutation type and aminoacidic position | Exon/Intron | dbSNP; References | CADD§/Alamut | Pathogenicity |
|---|---|---|---|---|---|---|
| GROUP 1—patients with Mild mutations | ||||||
| 1 | c.1700G>C | Missense p. (Gly567Ala) | 24 | rs104886137 (14) | 26§ | R |
| 2 | c.2473G>A | Missense p. (Gly825Arg) | 30 | None | 27§ | P |
| 3 | c.1957G>T | Missense p. (Gly653Trp) | 26 | LOVD database | 38§ | R |
| 4 | c.1835G>A | Missense p. (Gly612Asp) | 25 | rs281874680 (15) | 28§ | R |
| 5 | c.3695G>C | Missense p. (Gly1232Ala) | 41 | LOVD database | 27§ | R |
| 6 | c.4562G>A | Missense p. (Cys1521Tyr) | 48 | LOVD database | 31§ | R |
| 7 | c.938G>T | Missense p. (Gly313Val) | 17 | LOVD database | 33§ | R |
| 8 | c.629G>A | Missense p. (Gly210Glu) | 11 | LOVD database | 25§ | R |
| 9 | c.2918G>A | Missense p. (Gly973Asp) | 34 | (16) | 31§ | R |
| 10 | c.2077G>A | Missense p. (Gly693Arg) | 27 | (17) | 28§ | R |
| Pts | Nucleotide position | Mutation type and aminoacidic position | Exon/Intron | dbSNP; References | CADD§/Alamut† | Pathogenicity |
| GROUP 2—patients with Severe mutations | ||||||
| 1 | c.546+5G>C | Acceptor splice site | Intron 9 | None | Affects splicing | P |
| 2 | c.2245-40A>G* | Acceptor splice site-branch site r.2245_2395de; p.? # | 29 | rs1569495747 (13) | Affects splicing | R |
| 3 | c.646-1 G>T | Donor splice site | Intron 11 | None | Affects splicing | R |
| 4 | c.446del | c.446del p.Pro149Leufs*6 frameshift deletion (Inframe deletion) | 12 | rs104886054 (18) | Not available | R |
| 5 | c.3700C>T | Nonsense c.3700C>T p.Gln1234* | 41 | Rs281874719 (19) | 40§ | R |
| 6 | c.796C>T | Nonsense p. (Arg266*) | 14 | rs104886071 (20) | 36§ | R |
| 7 | c. 1117C>T | Nonsense p. (Arg373*) | 19 | rs107829929 (21) | 36§ | R |
| 8 | c.1845del | Frameshift p. (Asn616Ilefs*2) | 25 | None | Not available | P |
| 9 | c.649_656del | Frameshift p. (Asn217Leufs*9) | 12 | LOVD database | Not available | R |
| 10 | c.3274delG | Frameshift p. (Asn1093Thrfs*59) | 37 | None | Not available | P |
| 11 | c.2184delG | Frameshift p. (Gly728Glyfs*8) | 28 | LOVD database | Not available | R |
| 12 | c.4793_4798delinsTT (COL4A5) c.2765 G>T (COL4A3) |
Frameshift p. (Ser1598Phefs*2) (COL4A5) Missense p. (Gly922Glu) (COL4A3) |
49 34 |
None rs920413118 |
Not available 26§ |
P |
| 13 | c.2015G>A (COL4A5) c.5012_5013delGAinsTT (COL4A3) |
Missense p. (Gly672Asp) (COL4A5) stop-lost extension mutation p. (*1671Pheext*2) (COL4A3) |
26 52 |
LOVD database Not available |
27§
Not available |
R P |
| 14 | c.2245-40A>G** | Acceptor splice site-branch site r.2245_2395de; p.?# | 29 | rs1569495747 (13) | Affects splicing | R |
Pathogenicity of Mutations was compared with ARUP database and LOVD database. Presumption of pathogenicity was made by analysis with protein reconstruction software. R = reported as pathogenetic; P = presumed to be pathogenetic.
balanced X inactivation of both wild type and mutant alleles (11).
skewed X inactivation of wild type allele (11).
as a consequence of a variant destroying the exon 29 branch point, the sequence from nucleotide r.2245 to r.2395 (exon 29) is deleted from the transcript (11).
Pathogenicity of intron variants predicted using Alamut software v.2.11 (Interactive Biosoftware, Rouen, France), indicating functional impact of variants with relevant prediction tools included MaxEntScan, NNSPLICE, Human Splicing Finder, SpliceSiteFinder, GeneSplicer predictions tools.
Pathogenicity of missense variants predicted using the “Combined Annotation Dependent Depletion tool (CADD)”.