Table 8.
VKCFD1 in patients with GGCX mutations. This table gives an overview of all patients in the analyzed cohort with VKCFD1. For each patient, the GGCX mutations on both alleles and the affected protein domain are stated (protein annotation). Further, an overview of the coagulation factor function (percent of normal activity or in U/dL or U/mL), aPTT and PT is given, it is stated if patients were symptomatic within the first year of life. Reference values are stated between brackets if they were mentioned in the original article.
| Id | Allele 1 | Allele 2 | PT | INR | aPTT | FII | FVII | FIX | FX | Symptoms in 1st Year of Life | ||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Annotation | Protein Domain | Annotation | Protein Domain | |||||||||
| 1 | p.(L394R) | Glu-BS | p.(L394R) | Glu-BS | >120 s | - | >180 s | 2 U/dL [77–125 U/dL] | 3 U/dL [63–139 U/dL] | 8 U/dL [63–155 U/dL] | 2 U/dL [55–160 U/dL] | yes |
| 2 | p.(L394R) | Glu-BS | p.(L394R) | Glu-BS | - | - | - | 24 U/dL [77–125 U/dL] | 23 U/dL [63–139 U/dL] | 8 U/dL [63–155 U/dL] | 20 U/dL [55–160 U/dL] | yes |
| 3 | p.(L394R) | Glu-BS | p.(L394R) | Glu-BS | nd * | nd * | nd * | nd * | nd * | nd * | nd * | no |
| 4 | p.(L394R) | Glu-BS | p.(L394R) | Glu-BS | nd * | nd * | nd * | nd * | nd * | nd * | nd * | no |
| 5 | p.(W157R) | HTTM (TMD3) | p.(T591K) | RmlC-like | 49.5 s [11.5 s] | - | 60 s [30 s] | 9% * | 6% * | 7% * | 5% * | no |
| 6 | p.(W157R) | HTTM (TMD3) | p.(T591K) | RmlC-like | >60 s [11.5 s] | - | 56 s [30 s] | 14% * | 7% * | nd * | 7% * | no |
| 7 | p.(D153G) | HTTM (TMD3) | p.(M174R) | HTTM | 11% [70%–100%] | - | ratio 1.65 [0.84–1.21] | 26% [50%–150%] | <1% [50%–150%] | 12% [50%–150%] | 13% [50%–150%] | yes |
| 8 | p.(V255M) | HTTM | p.(S300F) | HTTM (TMD4) | 18.1 s [12–15 s] | 1.2 [0.8–1.2] | PTT: 43.3 s [25–41 s] | 64% [60%–150%] | 108% [60%–160%] | 62% [60%–160%] | 33% [60%–160%] | no |
| 9 | p.(V255M) | HTTM | p.(S300F) | HTTM (TMD4) | 21.6 s [12–15 s] | 1.9 [0.8–1.2] | 32.1 s [25–41 s] | 43% [60%–150%] | 31% [60%–160%] | 56% [60%–160%] | 18% [60%–160%] | no |
| 10 | p.(R83W) | HTTM | p.(Q374X) | TMD5 | 21–31 s [11–14 s] | - | - | 20% [65%–150%] | 74–117% [55%–185%] | 48–71% [50%–180%] | 20–22% [65%–185%] | no |
| 11 | p.(R83W) | HTTM | p.(Q374X) | TMD5 | 21–31 s [11–14 s] | - | - | 18% [65%–150%] | 88% [55%–185%] | 56% [50%–180%] | 18% [65%–185%] | no |
| 12 | p.(M174R) | HTTM | p.(I532T) | RmlC-like | - | 2.76 [0.9–1.14] | ratio 1.44 [0.83–1.18] | 20% [70%–131%] | 34% [69%–134%] | 42% [71%–139%] | 20% [70%–13%] | no |
| 13 | p.(G72_L124del) | HTTM (TMD1 and -2) | p.(R485P) | near PP-BS | - | - | - | 21% * | 42% * | nd * | 36%* | no |
| 14 | p.(W501S) | PP-BS | p.(W501S) | PP-BS | >100 s | - | PTT: >100 s | nd * | <1% * | 9% * | 26% * | yes |
| 15 | c.214+1G>T (splice) | HTTM (TMD1) | c.1609+3A>G (splice) | near PP-BS + RmlC-like | 69.8 s [8.4–12.0 s] | 7 | 45 s [21–33 s] | 2% [70%–130%] | 3% [65%–140%] | 4% [65%–140%] | <3% [60%–130%] | yes |
| 16 | p.(W493S) | near PP-BS | p.(W493S) | near PP-BS | - | 1.81 [0.8–1.2] | - | 66% [90%–150%] | 26% [90%–150%] | 70% [90%–150%] | 15 [90%–150%] | no |
| 17 | p.(R476C) | near PP-BS | - | - | - | 1.97 [0.8–1.2] | - | 38% [90%–150%] | 50% [90%–150%] | 103% [90%–150%] | 20% [90%–150%] | no |
| 18 | p.(R476H) | near PP-BS | - | - | - | 2.19 [0.8–1.2] | - | 38% [90%–150%] | 62% [90%–150%] | 90% [90%–150%] | 17% [90%–150%] | no |
| 19 | p.(Q374X) | TMD5 | p.(G537A) | RmlC-like | - | 1.7 [0.8–1.2] | - | 20% [90%–150%] | 74% [90%–150%] | 48% [90%–150%] | 20% [90%–150%] | no |
| 20 | p.(Q374X) | TMD5 | p.(G537A) | RmlC-like | - | 1.9 [0.8–1.2] | - | 18% [90%–150%] | 88% [90%–150%] | 56% [90%–150%] | 18% [90%–150%] | no |
| 21 | p.(H404P) | Glu-BS | p.(R485P) | near PP-BS | - | - | - | 35% * | 37% * | 54% * | 13%* | no |
| 22 | p.(W315X) | HTTM | p.(R485P) | near PP-BS | - | - | - | 30% * | 37% * | 53% * | 29% * | no |
| 23 | p.(R204C) | HTTM | p.(R204C) | HTTM | - | - | - | - | 15% (after VK R/) * | - | 6% * | yes |
| 24 | p.(R204C) | HTTM | p.(R204C) | HTTM | - | - | - | - | 31% * | - | 20% * | no |
| 25 | p.(R83P) | HTTM | p.(R83P) | HTTM | - | 1.7 * | - | 27% * | 77% * | 56% * | 33% * | no |
| 26 | p.(R204C) | HTTM | p.(R204C) | HTTM | - | - | - | - | - | nd * | nd * | yes |
| 27 | p.(W157R) | HTTM (TMD3) | c.2085-5T>C (splice) | near Gla domain | - | - | - | - | 54% * | - | 28% * | no |
| 28 | p.(S284P) | HTTM | p.(W315X) | HTTM | - | - | - | 41% * | 27% * | nd * | 18% * | no |
| 29 | p.(G125R) | HTTM (TMD2) | p.(D534V) | near PP-BS + RmlC-like | - | - | - | 30% * | 49% * | nd * | 28% * | no |
| 30 | p.(W501S) | PP-BS | p.(W501S) | PP-BS | 95% * | 35% * | nd * | 30% * | yes | |||
| 31 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | - | - | - | - | - | - | - | no VKCFD1 |
| 32 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 33.2 s [25–45 s] | 76.2% [70%–80%] | 86.5% [>60%] | 70.5% [64%–84%] | 67.1% [53%–122%] | no VKCFD1 |
| 33 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 36.2 s [25–45 s] | 73.2% [70%–80%] | 94.8% [>60%] | 68.7% [64%–84%] | 72.4% [53%–122%] | no VKCFD1 |
| 34 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 38.5 s [25–45 s] | 78.8% [70%–80%] | 119.3% [>60%] | 69.8% [64%–84%] | 58.3% [53%–122%] | no VKCFD1 |
| 35 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 32.6 s [25–45 s] | 74.1% [70%–80%] | 126.7% [>60%] | 69% [64%–84%] | 66.8% [53%–122%] | no VKCFD1 |
| 36 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 94.7% [80%–100%] | - | PTT: 43.1 s [25–45 s] | 73.1% [70%–80%] | 76.3% [>60%] | 70.4% [64%–84%] | 71.2% [53%–122%] | no VKCFD1 |
| 37 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 31.5 s [25–45 s] | 83% [70%–80%] | 79% [>60%] | 76.9% [64%–84%] | 58% [53%–122%] | no VKCFD1 |
| 38 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | - | - | - | - | - | - | - | no VKCFD1 |
| 39 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 37.8 s [25–45 s] | 77.8% [70%–80%] | 73.7% [>60%] | - | 55.9% [53%–122%] | no VKCFD1 |
| 40 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | - | - | - | - | - | - | - | no VKCFD1 |
| 41 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 96.4% [80%–100%] | - | PTT: 38.9 s [25–45 s] | 78.1% [70%–80%] | 81.9% [>60%] | 70% [64%–84%] | 67.7% [53%–122%] | no VKCFD1 |
| 42 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 38.9 s [25–45 s] | 74.2% [70%–80%] | 129.3% [>60%] | 68.5% [64%–84%] | 72.8% [53%–122%] | no VKCFD1 |
| 43 | p.(F74_G125del) | HTTM (TMD1 and -2) | p.(F74_G125del) | HTTM (TMD1 and -2) | 100% [80%–100%] | - | PTT: 31.8 s [25–45 s] | 76% [70%–80%] | 106% [>60%] | 68.6% [64%–84%] | 71.5% [53–122%] | no VKCFD1 |
| 44 | /(14 bp del I1) | - | /(14 bp del I1) | - | >100 s | - | >150 s | 0.35 U/mL * | 0.08 U/mL * | nd † | 0.21 U/mL * | yes |
| 45 | /(14 bp del I1) | - | /(14 bp del I1) | - | 30 s | - | 38 s | 0.09 U/mL * | 0.21 U/mL * | 0.59 U/mL | 0.17 U/mL * | no |
| 46 | p.(W493C) | near PP-BS | p.(R704X) | near Gla-domain | >100 s [12.8 s] | - | - | 3% * | 2% * | - | 3% * | yes |
| 47 | p.(D15_F71del) | N-terminus + HTTM (TMD1) | p.(D15_F71del) | N-terminus + HTTM (TMD1) | 98.9 s | 9 | 53.1 s | 2% * | 1.7% * | 4.7% * | 2% * | no |
14 bp del I1: 14 base pair deletion intron 1; aPTT: activated partial thromboplastin time; FII: coagulation factor II; FVII: coagulation factor VII; FIX: coagulation factor IX; FX: coagulation factor X; Glu-BS: glutamate binding site; HTTM: horizontally transferred transmembrane domain; Id: identification number; INR: international normalized ratio; nd: not described; PT: prothrombin time; PP-BS: propeptide binding site; RmlC: deoxythymidine-6-deoxy-d-xylo-4-hexulose 3,5 epimerase (EC5.1.3.13); RmlC-like: RmlC-like jelly roll fold; splice: splice site mutation; TMD: transmembrane domain; VK R/: vitamin K therapy; * no reference values in original article or no values, but clearly stated in full-text as deficient.† deficient factor IX confirmed at 9 years of age.