Table 3.
Sibling pairs with a discordant age at onset
| Family |
ABCA4 nucleotide changes |
ABCA4 protein changes |
Age‐at‐onset difference (yrs) | Sex youngest onset (age onset in yrs) | Sex oldest onset (age onset in yrs) |
|---|---|---|---|---|---|
| 5 | c.5537T>C(;)5603A>T | p.(Ile1846Thr)(;)(Asn1868Ile) | 37 | Female (15) | Male (52) |
| c.5882G>A | p.(Gly1961Glu) | ||||
| 12 | c.5603A>T | p.(Asn1868Ile) | 33 | Female (37) | Male (70) |
| c.5762_5763dup | p.(Ala1922Trpfs*18) | ||||
| 15 | c.3191‐2_3191del | p.(?) | 11 | Male (40) | Male (51) |
| c.5603A>T | p.(Asn1868Ile) | ||||
| 16 | Not tested | 11 | Male (21) | Male (32) | |
| 17 | c.1822T>A | p.(Phe608Ile) | 13 | Male (17) | Male (30) |
| c.2588G>C a | p.[Gly863Ala, Gly863del] | ||||
| 23 | c.2921_3328 + 2del | p.(Ser974_Gly1110delinsCys) | 26 | Male (13) | Male (39) |
| c.5059A>T | p.(Ile1687Phe) | ||||
| 27 | c.768G>T | p.(Leu257Valfs*17) | 22 | Female (49) | Female (71) |
| c.5603A>T | p.(Asn1868Ile) | ||||
| 28 | c.4539 + 2001G>A | p.[=, Arg1514Leufs*36] | 31 | Female (16) | Male (47) |
| c.5882G>A | p.(Gly1961Glu) | ||||
| 35 | c.859‐506G>C | p.[Phe287Thrfs*32,=] | 15 | Female (12) | Male (17) |
| c.5196 + 1137G>A | p.[=, Met1733Glufs*78] | ||||
| 37 | c.768G>T | p.(Leu257Valfs*17) | 16 | Female (14) | Male (30) |
| c.5882G>A | p.(Gly1961Glu) | ||||
| 44 | c.2409_2410del | p.(Phe804Trpfs*3) | 17 | Female (8) | Male (25) |
| c.[2588G>C;5603A>T] (;)2802_2804del | p.[(Gly863Ala, Gly863del); (Asn1868Ile)](;)(Val935del) | ||||
| 48 | c.768G>T | p.(Leu257Valfs*17) | 24 | Female (19) | Male (43) |
| c.5603A>T | p.(Asn1868Ile) | ||||
| 78 | c.656G>C b | p.(Arg219Thr) | 20 | Female (37) | Male (57) |
| c.2588G>C a | p.[Gly863Ala, Gly863del] | ||||
| 88 | c.2588G>C a | p.[Gly863Ala, Gly863del] | 20 | Female (15) | Male (35) |
| c.5461‐10T>C a | p.[Thr1821Valfs*13, Thr1821Aspfs*6] | ||||
| 90 | c.3322C>T | p.(Arg1108Cys) | 14 | Female (38) | Female (52) |
| c.3398T>C | p.(Ile1133Thr) | ||||
| 92 | c.768G>T | p.(Leu257Valfs*17) | 14 | Female (58) | Female (72) |
| c.4253 + 43G>A | p.[=, Ile1377Hisfs*3] | ||||
| 94 | c.[769‐784C>T;5603A>T] | p.[=, Leu257Aspfs*3; Asn1868Ile] | 48 | Female (20) | Male (68) |
| c.4539 + 1G>T | p.(?) | ||||
| 200 | c.768G>T | p.(Leu257Valfs*17) | 18 | Male (17) | Male (35) |
| c.2588G>C a | p.[Gly863Ala, Gly863del] |
Allele 1 in white, allele 2 in grey. Family 5, 35, 37, 44 were previously described by Valkenburg et al. 2019 (Valkenburg et al. 2019)
a
Variant c.5603A>T is often present on the same allele as c.2588G>C and c.5461‐10T>C. The c.5603A>T was not associated with the disease at the time of genetic analysis in these patients and therefore not reported.
b
Variants c.656G>C and c. 2588G>C are known to occur on the same allele. Segregation analysis was however not performed.