Background
Methods
Study subjects
Semen analysis and assisted reproductive therapies
Mutation analysis of PKD1, PKD2, and GANAB
Evaluation of the pathogenicity of variations
Results
Mutation analysis of PKD1, PKD2, and GANAB
cDNA change | Exon/ intron | Amino acid change | Mutation Type | Family No. | Family history | Known/Novel |
---|---|---|---|---|---|---|
PKD1
| ||||||
c.74dupG | 1 | p.Gly25Glyfs*89 | Frameshift | 29 | Yes | Novel |
c.106_107insT | 1 | p.Pro36Leufs*78 | Frameshift | 12 | Yes | Novel |
c.467_487del21 | 4 | p.Ala156_Ala162del | In-frame deletion | 49 | Yes | Novel |
c.856_862delTCTGGCC | 5 | p.Ser286Serfs*2 | Frameshift | 30 | Yes | Known |
c.1198C > T | 5 | p.Arg400* | Nonsense | 17 | Yes | Known |
c.1297C > T | 6 | p.Gln433* | Nonsense | 48 | NA | Known |
c.2050A > T | 10 | p.Arg684* | Nonsense | 47 | Yes | Novel |
c.2659delT | 11 | p.Trp887Glyfs*11 | Frameshift | 50 | Yes | Known |
c.2670 + 1G > A | IVS14 | - | Splice | 19 | Yes | Novel |
c.4177C > T | 15 | p.Gln1393* | Nonsense | 51 | Yes | Novel |
c.4447C > T | 15 | p.Gln1483* | Nonsense | 13 | Yes | Known |
14 | Yes | |||||
c.4551C > A | 15 | p.Tyr1517* | Nonsense | 39 | Yes | Novel |
c.4609G > T | 15 | p.Glu1537* | Nonsense | 31 | Yes | Known |
c.4846G > T | 15 | p.Glu1616* | Nonsense | 37 | Yes | Novel |
c.4957C > T | 15 | p.Gln1653* | Nonsense | 16 | Yes | Known |
c.5014_5015delAG | 15 | p.Arg1672Glyfs*98 | Frameshift | 53 | Yes | Known |
c.5120G > A | 15 | p.Trp1707* | Nonsense | 26 | Yes | Known |
c.5637C > G | 15 | p.Tyr1879* | Nonsense | 20 | Yes | Novel |
c.6115C > T | 15 | p.Gln2039* | Nonsense | 55 | Yes | Known |
c.6199C > T | 15 | p.Gln2067* | Nonsense | 34 | Yes | Known |
c.6804delG | 15 | p.Trp2268Cysfs*46 | Frameshift | 63 | No | Novel |
c.6813_6814delAC | 15 | p.Arg2272Glyfs*147 | Frameshift | 7 | Yes | Known |
c.6945_6946insT | 16 | p.Gly2316Trpfs*104 | Frameshift | 1 | Yes | Novel |
c.7126C > T | 17 | p.Gln2376* | Nonsense | 45 | Yes | Known |
c.7863 + 1G > C | IVS20 | - | Splice | 36 | Yes | Novel |
c.7863 + 2 T > G | IVS20 | - | Splice | 11 | Yes | Novel |
c.7915C > T | 21 | p.Arg2639* | Nonsense | 54 | Yes | Known |
c.7973_7974delTG | 21 | p.Val2658Glyfs*2 | Frameshift | 9 | Yes | Known |
c.8338G > T | 23 | p.Glu2780* | Nonsense | 27 | Yes | Known |
c.9666_9667delGA | 28 | p.Glu3222Aspfs*30 | Frameshift | 32 | Yes | Novel |
c.10050 + 1G > A | IVS30 | - | Splice | 44 | Yes | Known |
c.10220 + 2 T > C | IVS32 | - | Splice | 3 | Yes | Known |
c.10397C > G | 34 | p.Ser3466* | Nonsense | 6 | Yes | Novel |
c.10524_10525delAG | 35 | p.Glu3509Aspfs*117 | Frameshift | 2 | NA | Novel |
c.10710_10715delGGCTGT | 36 | p.3571_3572del2 | In-frame deletion | 40 | Yes | Known |
c.10724G > A | 36 | p.Try3575* | Nonsense | 38 | NA | Novel |
c.10896_10897delGA | 37 | p.Ser3633Profs*88 | Frameshift | 5 | No | Novel |
c.11240delC | 39 | p.Pro3747Hisfs*79 | Frameshift | 33 | Yes | Novel |
c.11269 + 1G > A | IVS39 | - | Splice | 10 | Yes | Novel |
c.11311_11312insGTGCT | 40 | p.Ser3771Cysfs*57 | Frameshift | 41 | NA | Novel |
c.11512C > T | 41 | p.Gln3838* | Nonsense | 15 | Yes | Known |
c.11538-2A > G | IVS41 | - | Splice | 18 | Yes | Known |
c.11617_11637del21 | 42 | p.3873_3879del7 | In-frame deletion | 4 | Yes | Novel |
c.11699_11700ins10 | 42 | p.Leu3901Alafs*63 | Frameshift | 22 | Yes | Novel |
c.11830_11838dup | 43 | p.Leu3944_Ala3946dup | In-frame duplication | 52 | Yes | Novel |
c.12101delT | 44 | p.Val4034Glyfs*5 | Frameshift | 25 | No | Novel |
c.12139-2A > T | IVS44 | - | Splice | 24 | Yes | Novel |
c.12391G > T | 45 | p.Glu4131* | Nonsense | 43 | Yes | Known |
c.12570_12571insCTCC | 46 | p.Ser4190Serfs*21 | Frameshift | 28 | Yes | Novel |
c.12682C > T | 46 | p.Arg4228* | Nonsense | 21 | Yes | Known |
23 | Yes | |||||
c.12712C > T | 46 | p.Gln4238* | Nonsense | 46 | Yes | Known |
EX31-33del | 31–33 | - | Large deletion | 72 | No | Novel |
PKD2
| ||||||
c.973C > T | 4 | p.Arg325* | Nonsense | 8 | Yes | Known |
c.1094 + 3_1094 + 6delAAGT | IVS4 | - | Splice | 35 | Yes | Known |
c.2159dupA | 11 | p.Asn720Lysfs*5 | Frameshift | 42 | Yes | Known |
cDNA change | Exon | Amino acid change | Co-occurence | SIFT | PolyPhen-2 | Mutation Taster | Family No. | Family history | Segregation | Known/Novel | Classification |
---|---|---|---|---|---|---|---|---|---|---|---|
PKD1
| |||||||||||
c.1385G>T | 6 | p.Arg462Met | NT | PRD | D | 77 | Yes | Yes | Novel | LP | |
c.2039A > T | 10 | p.Tyr680Phe | p.Tyr1879* | NT | POD | P | 20 | Yes | Yes | Known | LB |
c.2180 T>C | 11 | p.Leu727Pro | NT | PRD | D | 69 | Yes | Yes | Known | LP | |
c.2897G>C | 12 | p.Arg966Pro | NT | PRD | D | 73 | Yes | Yes | Novel | LP | |
c.3548C > G | 15 | p.Ser1183Trp | p.Gln1653* | NT | B | P | 16 | Yes | Yes | Novel | LB |
c.3613G>C | 15 | p.Asp1205His | NT | POD | P | 64 | Yes | Yes | Novel | LP | |
76 | No | NA | |||||||||
c.3868C > G | 15 | p.Leu1290Val | p.Gln1653* | T | B | P | 16 | Yes | Yes | Novel | LB |
c.3931G>A | 15 | p.Ala1311Thr | NT | B | P | 80 | No | No | Known | LB | |
c.4273C > T | 15 | p.Arg1425Cys | p.Gln3838* | NT | B | P | 15 | Yes | Yes | Novel | LB |
c.5600A > G | 15 | p.Asn1867Ser | p.Arg400* | NT | PRD | D | 17 | Yes | Yes | Novel | USV |
c.5957C>T | 15 | p.Thr1986Met | NT | PRD | P | 87 | Yes | NA | Novel | LB | |
c.6658C>T | 15 | p.Arg2220Trp | NT | PRD | D | 85 | Yes | Yes | Known | LP | |
c.6704C>T | 15 | p.Ser2235Leu | NT | PRD | D | 70 | Yes | Yes | Novel | LP | |
c.6827 T>C | 15 | p.Leu2276Pro | NT | PRD | D | 61 | Yes | Yes | Known | LP | |
c.6878C > T | 15 | p.Pro2293Leu | p.Pro36Leufs*78 | NT | POD | P | 12 | Yes | NA | Known | LB |
c.7099 T>C | 17 | p.Ser2367Pro | NT | PRD | D | 56 | Yes | NA | Novel | LP | |
c.7144A>C | 17 | p.Ser2382Arg | NT | PRD | D | 67 | Yes | Yes | Novel | LP | |
c.7241C > T | 18 | p.Thr2414Met | c.11269 + 1G > A | NT | PRD | D | 10 | Yes | Yes | Known | LP |
c.7589G>A | 19 | p.Gly2530Asp | NT | PRD | D | 59 | No | NA | Known | LP | |
c.8158A>C | 22 | p.Thr2720Pro | NT | PRD | D | 86 | NA | NA | Novel | LP | |
c.8311G>A | 23 | p.Glu2771Lys | NT | PRD | D | 83 | Yes | NA | Known | LP | |
c.8744A > G | 23 | p.Asn2915Ser | p.Ser4190Serfs*21 | T | B | D | 28 | Yes | Yes | Novel | USV |
c.8750C > T | 23 | p.Ala2917Val | p.Gln3838* | T | POD | P | 15 | Yes | Yes | Known | LB |
p.Gln1653* | 16 | Yes | Yes | ||||||||
c.10937 T>G | 37 | p.Val3646Gly | T | PRD | D | 68 | Yes | Yes | Novel | LP | |
c.10951G>A | 37 | p.Gly3651Ser | T | PRD | D | 79 | Yes | NA | Known | LP | |
c.11156G>T | 38 | p.Arg3719Leu | NT | PRD | D | 82 | Yes | Yes | Novel | LP | |
c.11248C>G | 39 | p.Arg3750Gly | NT | PRD | D | 74 | No | Yes | Known | LP | |
c.11257C>T | 39 | p.Arg3753Trp | NT | PRD | D | 84 | Yes | Yes | Known | LP | |
c.11351G > T | 40 | p.Gly3784Val | T | B | P | 75 | Yes | Yes | Novel | LB | |
c.11453G>A | 41 | p.Gly3818Asp | NT | PRD | D | 81 | Yes | Yes | Known | LP | |
c.11945A>C | 43 | p.Gln3982Pro | NT | PRD | P | 78 | Yes | Yes | Novel | LP | |
c.12671C>A | 46 | p.Thr4224Asn | NT | POD | P | 66 | Yes | NA | Novel | USV | |
PKD2
| |||||||||||
c.965G>A | 4 | p.Arg322Gln | NT | PRD | D | 64 | Yes | NA | Known | LP | |
GANAB
| |||||||||||
c.518G>A | 5 | p.Arg173Gln | T | PRD | D | 58 | Yes | NA | Novel | B | |
86 | NA | NA | |||||||||
c.991C>T | 10 | p.Arg331Cys | NT | PRD | D | 61 | Yes | No | Novel | LB | |
c.1078A>G | 11 | p.Met360Val | NT | B | D | 62 | Yes | NA | Novel | USV | |
c.367C>G | 4 | p.Pro123Ala | T | POD | D | 69 | Yes | Yes | Novel | USV | |
c.2292A>G | 19 | p.Ile764Met | T | B | D | Yes | Novel | USV |
Evaluation of the pathogenicity of variations
Correlation with male infertility
Gene | cDNA change | Exon/ intron | Amino acid change | Predicted location within PKD1 domains | Family No. | Agea | Inheriting/ageb | Semen analysis |
---|---|---|---|---|---|---|---|---|
PKD1 | c.856_862delTCTGGCC | 5 | p.Ser286Serfs*2 | Ig-like repeat domain | 30 | 27 | maternal | oligoasthenozoospermia |
PKD1 | c.1385G>T | 6 | p.Arg462Met | C-type lectin domain | 77 | 30 | paternal/25 | asthenozoospermia |
PKD1 | c.2527 T > C | 11 | p.Ser843Pro | not defined | 45 | 34 | paternal/22 | oligoasthenozoospermia |
PKD1 | c.7126C > T | 17 | p.Gln2376* | REJ | ||||
PKD1 | c.2670 + 1G > A | IVS14 | – | Ig-like repeat domain | 19 | 34 | maternal | asthenozoospermia |
PKD1 | c.3613G>C | 15 | p.Asp1205His | Ig-like repeat domain | 64 | 30 | paternal/28 | asthenozoospermia |
PKD2 | c.965G>A | 4 | p.Arg322Gln | – | ||||
PKD1 | c.4447C > T | 15 | p.Gln1483* | Ig-like repeat domain | 13 | 30 | paternal/25 | oligoasthenozoospermia |
PKD1 | c.4551C > A | 15 | p.Tyr1517* | Ig-like repeat domain | 39 | 31 | maternal | asthenozoospermia |
PKD1 | c.4609G > T | 15 | p.Glu1537* | Ig-like repeat domain | 31 | 37 | paternal/29 | asthenozoospermia |
PKD1 | c.5957C>T | 15 | p.Thr1986Met | Ig-like repeat domain | 87 | 38 | paternal/23 | asthenozoospermia |
PKD1 | c.6115C > T | 15 | p.Gln2039* | Ig-like repeat domain | 55 | 36 | paternal/25 | asthenozoospermia |
PKD1 | c.6199C > T | 15 | p.Gln2067* | Ig-like repeat domain | 34 | 23 | maternal | oligoasthenozoospermia |
PKD1 | c.6658C>T | 15 | p.Arg2220Trp | REJ | 85 | 31 | paternal/22 | oligoasthenozoospermia |
PKD1 | c.6704C>T | 15 | p.Ser2235Leu | REJ | 70 | 30 | paternal/29 | asthenozoospermia |
PKD1 | c.7241C > T | 18 | p.Thr2414Met | REJ | 10 | 30 | maternal | oligoasthenozoospermia |
PKD1 | c.11269 + 1G > A | IVS39 | – | not defined | ||||
PKD1 | c.7863 + 1G > C | IVS20 | – | REJ | 36 | 42 | maternal | oligoasthenozoospermia |
PKD1 | c.7863 + 2 T > G | IVS20 | – | REJ | 11 | 33 | maternal | asthenozoospermia |
PKD1 | c.7915C > T | 21 | p.Arg2639* | REJ | 54 | 35 | paternal/32 | asthenozoospermia |
PKD1 | c.7973_7974delTG | 21 | p.Val2658Glyfs*2 | REJ | 9 | 33 | paternal/28 | asthenozoospermia |
PKD1 | c.8744A > G | 23 | p.Asn2915Ser | not defined | 28 | 34 | maternal | oligoasthenozoospermia |
PKD1 | c.12570_12571insCTCC | 46 | p.Ser4190Serfs*21 | not defined | ||||
PKD1 | c.9666_9667delGA | 28 | p.Glu3222Aspfs*30 | not defined | 32 | 29 | paternal/24 | oligoasthenozoospermia |
PKD1 | EX31-33del | 31–33 | – | not defined | 72 | 35 | de novo | oligozoospermia |
PKD1 | c.10220 + 2 T > C | IVS32 | – | not defined | 3 | 44 | NA | oligoasthenozoospermia |
PKD1 | c.12053C > T | 44 | p.Thr4018Ile | not defined | ||||
PKD1 | c.10397C > G | 34 | p.Ser3466* | not defined | 6 | 27 | paternal/22 | oligoasthenozoospermia |
PKD1 | c.10524_10525delAG | 35 | p.Glu3509Aspfs*117 | not defined | 2 | 28 | NA | oligoasthenozoospermia |
PKD1 | c.6804delG | 15 | p.Trp2268Cysfs*46 | REJ | 63 | 35 | de novo | azoospermia |
PKD1 | c.10710_10715delGGCTGT | 36 | p.3571_3572del2 | Putative TM region | 40 | 34 | maternal | asthenozoospermia |
PKD1 | c.10896_10897delGA | 37 | p.Ser3633Profs*88 | not defined | 5 | 37 | de novo | oligoasthenozoospermia |
PKD1 | c.10937 T>G | 37 | p.Val3646Gly | not defined | 68 | 32 | paternal/26 | asthenozoospermia |
PKD1 | c.10951G>A | 37 | p.Gly3651Ser | not defined | 79 | 35 | maternal | oligoasthenozoospermia |
PKD1 | c.11240delC | 39 | p.Pro3747Hisfs*79 | not defined | 33 | 33 | paternal/25 | oligoasthenozoospermia |
PKD1 | c.11538-2A > G | IVS41 | – | not defined | 18 | 36 | paternal/30 | oligoasthenozoospermia |
PKD1 | c.11617_11637del21 | 42 | p.3873_3879del7 | not defined | 4 | 25 | NA | asthenozoospermia |
PKD1 | c.11699_11700ins10 | 42 | p.Leu3901Alafs*63 | Putative TM region | 22 | 29 | paternal/22 | asthenozoospermia |
PKD1 | c.11830_11838dup | 43 | p.Leu3944_Ala3946dup | Putative TM region | 52 | 26 | paternal/21 | oligoasthenozoospermia |
PKD1 | c.11945A>C | 43 | p.Gln3982Pro | Putative TM region | 78 | 33 | paternal/28 | asthenozoospermia |
PKD1 | c.12712C > T | 46 | p.Gln4238* | not defined | 46 | 34 | maternal | asthenozoospermia |
PKD3 | c.518G>A | 5 | p.Arg173Gln | – | 58 | 37 | paternal/27 | asthenozoospermia |
PKD1 | c.1198C > T | 5 | p.Arg400* | not defined | 17 | 29 | maternal | normal |
PKD1 | c.5600A > G | 15 | p.Asn1867Ser | Ig-like repeat domain | ||||
PKD1 | c.3931G>A | 15 | p.Ala1311Thr | Ig-like repeat domain | 80 | 27 | de novo | normal |
PKD1 | c.2039A > T | 10 | p.Tyr680Phe | not defined | 20 | 27 | paternal/27 | normal |
PKD1 | c.5637C > G | 15 | p.Tyr1879* | Ig-like repeat domain | ||||
PKD1 | c.4273C > T | 15 | p.Arg1425Cys | Ig-like repeat domain | 15 | 31 | paternal/28 | normal |
PKD1 | c.8750C > T | 23 | p.Ala2917Val | not defined | ||||
PKD1 | c.11512C > T | 41 | p.Gln3838* | Putative TM region | ||||
PKD1 | c.6813_6814delAC | 15 | p.Arg2272Glyfs*147 | REJ | 7 | 32 | NA | normal |
PKD1 | c.7144A>C | 17 | p.Ser2382Arg | REJ | 67 | 29 | maternal | normal |
PKD1 | c.10050 + 1G > A | IVS30 | – | not defined | 44 | 40 | paternal/30 | normal |
PKD1 | c.12139-2A > T | IVS44 | – | Putative TM region | 24 | 34 | maternal | normal |
PKD2 | c.2159dupA | 11 | p.Asn720Lysfs*5 | – | 42 | 29 | maternal | normal |
Gene | cDNA change | Amino acid change | Family No. | Semen analysis | Treatment methods |
---|---|---|---|---|---|
PKD1 | c.856_862delTCTGGCC | p.Ser286Serfs*2 | 30 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.1385G>T | p.Arg462Met | 77 | asthenozoospermia | ICSI+PGD |
PKD1 | c.2527 T > C | p.Ser843Pro | 45 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.7126C > T | p.Gln2376* | |||
PKD1 | c.2670 + 1G > A | – | 19 | asthenozoospermia | ICSI+PGDa |
PKD1 | c.4447C > T | p.Gln1483* | 13 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.4551C > A | p.Tyr1517* | 39 | asthenozoospermia | natural pregnant |
PKD1 | c.4609G > T | p.Glu1537* | 31 | asthenozoospermia | ICSI+PGD |
PKD1 | c.6199C > T | p.Gln2067* | 34 | oligoasthenozoospermia | natural pregnant |
PKD1 | c.6658C>T | p.Arg2220Trp | 85 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.6704C>T | p.Ser2235Leu | 70 | asthenozoospermia | ICSI+PGD |
PKD1 | c.7863 + 1G > C | – | 36 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.7863 + 2 T > G | – | 11 | asthenozoospermia | ICSI+PGD |
PKD1 | c.10529C > T | p.Thr3510Met | |||
PKD1 | c.7915C > T | p.Arg2639* | 54 | asthenozoospermia | ICSI+PGD |
PKD1 | c.7973_7974delTG | p.Val2658Glyfs*2 | 9 | asthenozoospermia | ICSI |
PKD1 | c.10529C > T | p.Thr3510Met | |||
PKD1 | c.8744A > G | p.Asn2915Ser | 28 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.12570_12571insCTCC | p.Ser4190Serfs*21 | |||
PKD1 | c.9666_9667delGA | p.Glu3222Aspfs*30 | 32 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.10220 + 2 T > C | – | 3 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.12053C > T | p.Thr4018Ile | |||
PKD1 | c.10524_10525delAG | p.Glu3509Aspfs*117 | 2 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.10896_10897delGA | p.Ser3633Profs*88 | 5 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.10937 T>G | p.Val3646Gly | 68 | asthenozoospermia | ICSI+PGD |
PKD1 | c.11240delC | p.Pro3747Hisfs*79 | 33 | oligoasthenozoospermia | ICSI+PGDa |
PKD1 | c.11538-2A > G | – | 18 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.11699_11700ins10 | p.Leu3901Alafs*63 | 22 | asthenozoospermia | ICSI+PGD |
PKD1 | c.11830_11838dup | p.Leu3944_Ala3946dup | 52 | oligoasthenozoospermia | ICSI+PGD |
PKD1 | c.11945A>C | p.Gln3982Pro | 78 | asthenozoospermia | ICSI+PGD |
PKD1 | c.12712C > T | p.Gln4238* | 46 | asthenozoospermia | ICSI+PGD |
PKD1 | c.1198C > T | p.Arg400* | 17 | normal | ICSI+PGD |
PKD1 | c.5600A > G | p.Asn1867Ser | |||
PKD1 | c.3931G>A | p.Ala1311Thr | 80 | normal | ICSI |
PKD1 | c.2039A > T | p.Tyr680Phe | 20 | normal | ICSI+PGDa |
PKD1 | c.5637C > G | p.Tyr1879* | |||
PKD1 | c.4273C > T | p.Arg1425Cys | 15 | normal | ICSI+PGDa |
PKD1 | c.8750C > T | p.Ala2917Val | |||
PKD1 | c.11512C > T | p.Gln3838* | |||
PKD1 | c.6813_6814delAC | p.Arg2272Glyfs*147 | 7 | normal | ICSI+PGD |
PKD1 | c.7144A>C | p.Ser2382Arg | 67 | normal | ICSI+PGD |
PKD1 | c.10050 + 1G > A | – | 44 | normal | ICSI+PGD |
PKD1 | c.12139-2A > T | – | 24 | normal | ICSI+PGD |
PKD2 | c.2159dupA | p.Asn720Lysfs*5 | 42 | normal | ICSI+PGD |