Table 3.
Patient | Renal Phenotypea | Extrarenal Phenotype | Causal Gene | NM_ref | Nucleotide Change | Protein Change | PP2 | Sift | MT | Granthamb | GVDVc | No. of Missense Deleterious Scores | Splice Effect, % | ExAC | Inheritance | Ref. |
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
Rare variants in individuals with CAKUT | ||||||||||||||||
K4 | RH | Bifid uterus | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | NAd | 36 | ||||||||
K50 | UMD+ | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | Affected mothere | |||||||||
K103 | RD+ | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | Affected mothere | |||||||||
K124 | RD+ | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | De novod | |||||||||
K143 | RD+ | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | De novod | |||||||||
K172 | UMD+ | Diabetes plus cryptorchidy | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | Affected motherf | |||||||||
K185 | RD | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | NAd | |||||||||
K203 | RD | No | HNF1B | 000458 | c.[(?_−30)_(*220_?)del];[=] | 0 | NAe | |||||||||
K170 | RH+ | No | HNF1B | 000458 | c.[344+2_+5del];[=] | −100 | 0 | NAd | ||||||||
K72 | RH | Papillary excavation | PAX2 | 003987 | c.[(?_−30)_(*220_?)del];[=] | 0 | Germinal mosaicism/two affected childrene | 37 | ||||||||
K62 | RH | Eye coloboma | PAX2 | 003987 | c.[?−30_410+?del];[=] | 0 | NAd | |||||||||
K79 | RD | Papillary coloboma | PAX2 | 003987 | c.[44−?_496+?del];[=] | 0 | De novod | |||||||||
K117 | RH | No | PAX2 | 003987 | c.[183C>A];[=] | p.[Ser61Arg];[=] | 1 | 0 | dc | 110 | C0 | 4/5 | 0 | De novod | ||
K133 | RH+ | Papillary coloboma | PAX2 | 003987 | c.[76del];[=] | p.[Val26Cysfs*3];[=] | 0 | Affected motherg | 38 | |||||||
K146 | RH+ | No | PAX2 | 003987 | c.[446del];[=] | p.[Pro149Glnfs*10];[=] | 0 | NAd | ||||||||
K148 | RH | No | PAX2 | 003987 | c.[76dup];[=] | p.[Val26Glyfs*28];[=] | 0 | Unaffected mother (somatic mosaicism)d | 39 | |||||||
K176 | RH+ | No | PAX2 | 003987 | c.[331G>A];[=] | p.[Ala111Thr];[=] | 0.998 | 0 | dc | 58 | C0 | 4/5 | 0 | Affected mothere | 40 | |
K199 | Oth | Papillary coloboma | PAX2 | 003987 | c.[212G>A];[=] | p.[Arg71Lys];[=] | 0.974 | 0 | dc | 26 | C0 | 3/5 | −49 | 0 | NAe,h | 41 |
K80 | UKA+ | Preauricular pit plus ear tag | EYA1 | 000503 | c.[557−?_1597+?del];[=] | 0 | Affected motheri | |||||||||
K78 | BKA | No | EYA1 | 000503 | c.[967–1G>C ]:[=] | −100 | 0 | Affected fathere | 42 | |||||||
K119 | RH | Branchial defect plus deafness | EYA1 | 000503 | c.[1459T>C];[=] | p.[Ser487Pro];[=] | 0.132 | 0.07 | dc | 74 | C0 | 2/5 | 0.0015% NFE | Affected fatheri | 43 | |
K135 | UKA | Preauricular pit | EYA1 | 000503 | c.[553C>T];[=] | p.[Gln185*];[=] | 0 | Affected motheri | 44 | |||||||
K145 | RH | Branchial defect | EYA1 | 000503 | c.[1338_1346del];[=] | p.[Asn446_Tyr448del];[=] | 0 | Affected fathere | ||||||||
K101 | UKA | Ear tag plus external ear canal stenosis | GATA3 | 001002295 | c.[(?_−30)_(*220_?)del];[=] | 0 | Affected fatherj | 45 | ||||||||
K167 | UKA | Deafness plus intellectual disability | GATA3 | 001002295 | c.[(?_−30)_(*220_?)del];[=] | 0 | NAd | |||||||||
K48 | RH+ | No | GATA3 | 001002295 | c.[829C>T];[=] | p.[Arg277*];[=] | 0 | De novod | 46 | |||||||
K158 | BKA | No | ANOS1 | 000216 | c.[?−30_255+?del] | 0 | Unaffected mothere | 47 | ||||||||
K26 | BKA | No | ANOS1 | 000216 | c.[769C>T];[=] | p.[Arg257*];[=] | 0 | NAd | 48 | |||||||
K160 | UKA | Deafness plus branchial defect plus colobomatous microphtalmia | CHD7 | 017780 | c.[5050G>A];[=] | p.[Gly1684Ser];[=] | 0.929 | 0 | dc | 56 | C55 | 5/5 | −38 | 0 | Fatherk | 49 |
K73 | RH+ | Lissencephaly plus agenesis of corpus callosum | KIF14 | 014875 | c.[3567−?_4072+?del];[(3567-?_4072+?del)] | 0 | NAd | |||||||||
K195 | BKA | Craniostenosis plus microcephaly plus agenesis of corpus callosum | KIF14 | 014875 | c.[3910C>T];[1090C>T] | p.[Gln1304*];[Arg364Cys] | 1 | 0 | dc | 180 | C0 | 4/5 | 0 | One mutation from each parente | ||
Rare variants in individuals with branchial signs and/or ear defect without CAKUT phenotype | ||||||||||||||||
BO4 | No | Branchial defect plus preauricular pit plus deafness | EYA1 | 000503 | c.[1081C>T];[=] | p.[Arg361*];[=] | 0 | De novod | 50 | |||||||
BO5 | No | Branchial defect plus deafness | SIX1 | 005982 | c.[273_274insC];[=] | p.[Tyr92Leufs*62];[=] | 0 | Affected motheri |
PP2, Polyphen2; MT, MutationTaster; GVDV, Grantham variation score and Grantham difference score; RH, renal hypoplasia; NA, not available; UMD, unilateral multicystic dysplasia; RD, renal dysplasia; Oth, other; UKA, unilateral kidney agenesis; BKA, bilateral kidney agenesis; NFE, non-Finnish European population.
Plus indicates presence of (a) secondary CAKUT phenotype(s).
Considered as deleterious when ≥50.
Considered as deleterious when ≥C25.
Patient with sporadic case.
Patient with familial case.
Parent affected with diabetes without renal defect.
Parent affected with coloboma without renal defect.
Mutation transmitted to a son with coloboma without renal defect.
Parent affected with BO without renal defect.
Parent affected with deafness without renal defect.
Clinical information not available.