Clinical characteristics and collagen gene mutations in 11 patients with Alport syndrome and their family members
| Family number | Family member (pedigree position) | Sex | Age, years* | Kidney disease (age, years†) | Hearing loss (age, years‡) | Ocular lesions | Mutation (nucleotide change; effect on protein) | ||
|---|---|---|---|---|---|---|---|---|---|
| COL4A3 | COL4A4 | COL4A5 | |||||||
| 1 | Proband (II:2) | M | 7 | Macroscopic haematuria (4) | No | No | c.2746+1G>T; p.? | c.1553G>A; p.Gly518Glu | None |
| 1 | Mother (I:1) | F | 45 | Haematuria | NA | No | c.2746+1G>T; p.? | Variant not present | NT |
| 1 | Father (I:2) | M | 43 | Ureteropelvic junction obstruction | NA | NA | Variant not present | c.1553G>A; p.Gly518Glu | NT |
| 2 | Proband (II:1) | F | 36 | Haematuria | No | No | c.898G>A; p.Gly300Arg | c.3452G>C; p.Gly1151Ala | None |
| 2 | Mother (I:1) | F | NA | Haematuria | NA | NA | c.898G>A; p.Gly300Arg | Variant not present | NT |
| 2 | Maternal grandfather | M | NA | ESRD (80) | NA | NA | NA | NA | NA |
| 2 | Father (I:2) | M | NA | Haematuria | NA | NA | Variant not present | c.3452G>C; p.Gly1151Ala | NT |
| 3 | Proband (I:2) | M | 55 | Proteinuria, CRF | Yes (39) | NA | c.1558G>C; p.Gly520Arg | c.4698delT; p.Cys1566Trpfs*37 | None |
| 3 | Mother | F | Dead, 88, cancer | None | No | NA | NA | NA | NT |
| 3 | Maternal uncle | M | Dead, 45, ESRD | ESRD (<45) | NA | NA | NA | NA | NT |
| 3 | Sister (I:1) | F | 60 | Pre-emptive renal transplantation (50) | Yes | NA | c.1558G>C; p.Gly520Arg | c.4698delT; p.Cys1566Trpfs*37 | NT |
| 3 | Father | M | NA, cancer | None | No | NA | NA | NA | NA |
| 3 | Daughter (II:2) | F | 23 | Intermittent haematuria | No | NA | Variant not present | c.4698delT; p.Cys1566Trpfs*37 | NT |
| 3 | Daughter (II:3) | F | 20 | Intermittent haematuria | No | NA | c.1558G>C; p.Gly520Arg | Variant not present | NT |
| 3 | Niece (II:1) | F | 28 | Haematuria | NA | NA | c.1558G>C; p.Gly520Arg | Variant not present | NT |
| 4 | Proband (III:1) | F | 36 | Haematuria, proteinuria | No | NA | c.1504+1G>A; p.? | c.1293_1310del; p.Lys434_Gly439del | None |
| 4 | Mother (II:1) | F | 64 | Haematuria | No | NA | c.1504+1G>A; p.? | Variant not present | NT |
| 4 | Father (II:2) | M | 80 | ESRD (68) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternal aunt (II:3) | F | 76 | ESRD (64) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternal granduncle (I:3) | M | Dead, ∼70 | Haematuria | No | NA | NA | NA | NA |
| 4 | Paternally related | M | 48 | Haematuria | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternal grandaunt (I:4) | F | Dead | Haematuria, proteinuria, ESRD | No | NA | NA | NA | NA |
| 4 | Paternally related | M | 47 | Haematuria, proteinuria, CRF (47) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternally related | F | 80 | Haematuria, proteinuria, CRF (70) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternally related | M | 69 | CRF (69) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternally related | F | NA | CRF (80) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternally related | F | 51 | ESRD (50) | No | NA | Variant not present | c.1293_1310del; p.Lys434_Gly439del | NT |
| 4 | Paternally related | NA | NA | ESRD (60) | No | NA | NA | NA | NA |
| 5 | Proband (II:1) | F | 3 | Macroscopic haematuria | No | No | c.2065G>A; p.Gly689Arg | c.1459+1G>A; p.? | None |
| 5 | Mother (I:1) | F | NA | Haematuria | No | NA | c.2065G>A; p.Gly689Arg | Variant not present | NT |
| 5 | Father (I:2) | M | NA | None | No | NA | Variant not present | c.1459+1G>A; p.? | NT |
| 6 | Proband (II:1) | F | 37 | Intermittent haematuria | NA | NA | c.4994G>A; p.Cys1665Tyr | c.2906C>G; p.Ser969X | None |
| 6 | Mother (I:1) | F | NA | None | NA | NA | Variant not present | Variant not present | NT |
| 6 | Father (I:2) | M | Dead | CRF (21); ESRD (40) | Yes | NA | NA | NA | NA |
| 7 | Proband (II:1) | M | 45 | Haematuria, proteinuria, CRF | Yes (32)§ | NA | del exon 1 | c.[1−?_192+?del];[=](del ex1–4) | None |
| 7 | Son (III:1) | M | 19 | None | No | NA | Variant not present | Variant not present | None |
| 7 | Father (I:2) | M | Dead, 40, ESRD | ESRD (<40) | NA | NA | NA | NA | NA |
| 7 | Paternal uncle (I:1) | M | Dead, 61, ESRD | ESRD (<61) | NA | NA | NA | NA | NA |
| 8 | Proband (I:1) | F | 54 | ESRD (44) | Yes | Yes | None | c.3817+1G>T; p.? | c.2858G>T; p.Gly953Val |
| 8 | Son (II:1) | M | 17 | Haematuria | NA | NA | NT | c.3817+1G>T; p.? | Variant not present |
| 9 | Proband (II:1) | F | 45 | Haematuria, proteinuria | Yes (34) | NA | None | c.2075G>T; p.Gly692Val | c.1931G>A; p.Gly644Asp |
| 9 | Mother (I:1) | F | 69 | Haematuria, proteinuria during pregnancies | No¶ | NA | NT | Variant not present | c.1931G>A; p.Gly644Asp |
| 9 | Son | M | 11 | Proteinuria | No | NA | NT | c.2075G>T; p.Gly692Val | Variant not present |
| 9 | Son | M | 9 | None | No | NA | NT | Variant not present | Variant not present |
| 9 | Paternal nephew | M | NA | Possible renal disease | Yes | NA | NA | NA | NA |
| 10 | Proband (II:1) | M | 26 | Haematuria, proteinuria | No | No | None | c.2164G>A; p.Gly722Ser | c.4042G>A; p.Gly1348Arg |
| 10 | Father (I:2) | M | 65 | NA | No | NA | NT | c.2164G>A; p.Gly722Ser | Variant not present |
| 10 | Mother (I:1) | F | 55 | NA | No | NA | NT | Variant not present | Variant not present |
| 11 | Proband (II:4) | F | 13 | Intermittent haematuria, proteinuria | No | NA | None | c.1623+5G>T; p.? c.4760C>G; p.(Pro1587Arg) | c.2051G>T; p.Gly684Val |
| 11 | Mother (I:1) | F | 32 | Haematuria, proteinuria | No | NA | NT | c.1623+5G>T; p.? | Variant not present |
| 11 | Father (I:2) | M | 33 | ESRD (25) | Yes | Yes | NT | c.4760C>G; p.(Pro1587Arg) | c.2051G>T; p.Gly684Val |
| 11 | Brother 1 (II:1) | M | 17 | Haematuria, proteinuria | No | NA | NT | c.1623+5G>T; p.? c.4760C>G; p.(Pro1587Arg) | Variant not present |
| 11 | Brother 2 (II:2) | M | 17 | Haematuria, proteinuria | No | NA | NT | c.4760C>G; p.(Pro1587Arg) | Variant not present |
| 11 | Sister 1 (II:3) | F | 14 | Haematuria, proteinuria | No | NA | NT | c.1623+5G>T; p.? | c.2051G>T; p.Gly684Val |
| 11 | Sister 2 (II:5) | F | 9 | Haematuria, proteinuria | No | NA | NT | c.1623+5G>T; p.? | c.2051G>T; p.Gly684Val |
| 11 | Sister 3 (II:6) | F | 5 | Haematuria | No | NA | NT | c.1623+5G>T; p.? | c.2051G>T; p.Gly684Val |
*Cause of death indicated when available.
†Age at diagnosis or intervention.
‡Age at diagnosis.
§−40 dB.
¶Tested at 65 years.
CRF, chronic renal failure; ESRD, end-stage renal disease; NA, data missing or DNA not available for analysis; NT, gene not tested in relatives because not mutated in proband.