Table 2.
Disease-associated variants identified by Sanger sequencing genotyping and MLPA analysis in Polish patients with C1-INH-HAE
| No. family | No. of case |
Sex | Age | C1-INH- HAE type |
Disease-associated varianta | ||||
|---|---|---|---|---|---|---|---|---|---|
| A. Sanger sequencing | |||||||||
| cDNA change | Protein change | Location | Mutation type | HGMD_MUTATIONb | |||||
| I | 1 | F | 59 | I | c.1249+5G>A | ? | intron 7 | Splice region variant | CS083985 |
| 2 | F | 30 | I | c.1249+5G>A | ? | intron 7 | Splice region variant | ||
| II | 3 | F | 56 | I | c.177_177delC | p.(L60Wfs*19) | exon 3 | Deletion variant, frameshift variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| 4 | M | 36 | I | c.177_177delC | p.(L60Wfs*19) | exon 3 | Deletion variant, frameshift variant | ||
| 5 | F | 31 | I | c.177_177delC | p.(L60Wfs*19) | exon 3 | Deletion variant, frameshift variant | ||
| III | 6 | M | 37 | I | c.667C>T | p.(Gln223Ter) | exon 4 | Nonsense variant | CM033456 |
| IV | 7 | F | 23 | II | c.1396C>T | p.(Arg466Cys) | exon 8 | Missense variant | CM890026 associated with type II |
| 8 | F | 29 | II | c.1396C>T | p.(Arg466Cys) | exon 8 | Missense variant | ||
| VI | 10 | F | 69 | I | c.1328A>C | p.(His443Pro) | exon 8 | Missense variant | CM004572 |
| VIII | 15 | M | 53 | II | c.1396C>T | p.(Arg466Cys) | exon 8 | Missense variant | CM890026 associated with type II |
| 16 | F | 30 | II | c.1396C>T | p.(Arg466Cys) | exon 8 | Missense variant | ||
| IX | 17 | F | 38 | II | c.1397G>T | p.(Arg466Leu) | exon 8 | Missense variant | CM92013 associated with type II |
| X | 18 | F | 22 | I | c.463C>G | p.(His155Asp) | exon 3 | Missense variant | Novelc MutationTaster: prediction disease causing, probability – 0.761d |
| XI | 19 | F | 35 | I | c.540_541insAG | p.(Val181Argfs*31) | exon 3 | Insertion variant, frameshift variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| XII | 20 | F | 52 | I | c.485_498delinsTGCTGAGA | p.(Lys162_Asn166delinsMetLeuArg | exon 3 | Deletion-insertion variant | Novelc MutationTaster: prediction disease causing, probability – 0.992 |
| 21 | F | 55 | I | c.485_498delinsTGCTGAGA | p.(Lys162_Asn166delinsMetLeuArg | exon 3 | Deletion-insertion variant | ||
| XVI | 25 | M | 58 | I | c.-22-19_-22-4delAGGCTGGCTGGCTCCG | None | intron 1 | Splice region variant | Novelc MutationTaster: prediction disease causing, probability – 1d |
| XIX | 28 | F | 47 | II | c.1396C>T | p.(Arg466Cys) | exon 8 | Missense variant | CM890026 associated with type II |
| XX | 29 | M | 44 | I | c.467C>A | p.(Ala156Asp) | exon 3 | Missense variant | CM087069 |
| XXII | 32 | F | 75 | I | c.733dupA | p.(Ser245Lysfs*12) | exon 5 | Duplication variant, frameshift variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| XXIII | 33 | F | 51 | I | c.990C>G | p.(Tyr330Ter) | exon 6 | Nonsense variant | CM960221 |
| XXIV | 34 | F | 41 | I | c.622C>T | p.(Gln208Ter) | exon 4 | Nonsense variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| XXV | 35 | M | 37 | I | c.1322T>C | p.(Met441Thr) | exon 8 | Missense variant | CM087089 |
| XXVI | 36 | F | 33 | II | c.1396C>A | p.(Arg466Ser) | exon 8 | Missense variant | CM900041 associated with type II |
| XXVIII | 38 | F | 43 | I | c.550G>A | p.(Gly184Arg) | exon 3 | Missense variant | BM1165483 |
| XXIX | 39 | M | 41 | I | c.79dupA | p.(Thr27Asnfs*31) | exon 3 | Duplication variant, frameshift variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| XXX | 40 | F | 29 | I | c.553_554insG | p.(Ala185Glyfs*72) | exon 4 | Insertion variant, frameshift variant | Novelc MutationTaster: prediction disease causing, probability – 1 |
| XXXI | 41 | F | 40 | I | c.152C>T | p.(Ser51Phe) | exon 3 | Missense variant | rs773505671 |
| B. MLPA analysis | |||||||||
| Change described at genomic DNA | Protein change | Location | Mutation type | ||||||
| VII | 11 | F | 61 | I | rsSERPING1-5(P243-SERPING1 - F12)x3 rsSERPING1-6(P243-SERPING1 - F12)x3 |
? | exon 5 and 6 | Gross duplication | |
| 12 | F | 33 | I | rsSERPING1-5(P243-SERPING1 - F12)x3 rsSERPING1-6(P243-SERPING1 - F12)x3 |
? | exon 5 and 6 | Gross duplication | ||
| 13 | M | 4 | I | rsSERPING1-5(P243-SERPING1 - F12)x3 rsSERPING1-6(P243-SERPING1 - F12)x3 |
? | exon 5 and 6 | Gross duplication | ||
| 14 | F | 29 | I | rsSERPING1-5(P243-SERPING1 - F12)x3 rsSERPING1-6(P243-SERPING1 - F12)x3 |
? | exon 5 and 6 | Gross duplication | ||
| XXI | 30 | F | 58 | I | rsSERPING1-8(P243-SERPING1 - F12)x1 | ? | exon 8 | Gross deletions | |
| 31 | F | 26 | I | rsSERPING1-8(P243-SERPING1 - F12)x1 | ? | exon 8 | Gross deletions | ||
| Total | 26 F 8 M |
I – 27 II – 7 |
|||||||
F – female, M – male, a all disease-associated variants were present in the heterozygous state, β HGMD – the Human Gene Mutation Database, c novel disease-associated variant, not previously described, d uncertain significance, variant probably leading to C1-INH-HAE, confirmation of functional analysis required