Table 2.
Molecular characterization, X-inactivation pattern and transcriptional analysis results in symptomatic and asymptomatic carriers
| Carrier ID | Classification | DMD mutation(a) | X-inactivation pattern | RNA profiling | Transcripts representation (wt:mutated) | Total transcript level | WT transcript level |
|---|---|---|---|---|---|---|---|
|
C1 |
Symptomatic |
t(X;9)(p21.1;p22.1) |
100:0 (blood) 100:0 (sk.m.) |
Biallelic transcript (biallelic pol. 3’-UTR) |
nd |
nd |
nd |
|
C2 |
Symptomatic |
Dup exons 3–7 c.94-?_649 + ?dup (out of frame) |
60:40 |
WT + DUP 3–7 transcripts |
nd |
nd |
nd |
|
C3 |
Symptomatic |
Dup exons 5–7 c.265-?_649 + ?dup (out of frame) |
75:25 |
WT + DUP 5–7 transcripts |
70:30 |
nd |
nd |
|
C4 |
Symptomatic |
Del exons 8–9 c.650-?_960 + ?del (out of frame) |
86:14 |
WT + DEL 8–9 transcripts |
50:50 |
17% (ex 12) 12% (ex 55) |
9% (ex 12) 6% (ex 55) |
|
C5 |
Symptomatic |
Del exon 44 c.6291-?_6438 + ?del (out of frame) |
Non Informative |
WT + DEL 44 transcripts |
88:12 |
109% (ex 12) 31% (ex 55) |
96% (ex 12) 27% (ex 55) |
|
C6 |
Symptomatic |
Del exon 54 c.7873-?_8027 + ?del (out of frame) |
54:46 |
WT + DEL 54 transcripts |
89:11 |
46% (ex 12) 78% (ex 55) |
41% (ex 12) 69% (ex 55) |
|
C7 |
Symptomatic |
Del exons 8–48 c.650-?_7098 + ?del (out of frame) |
34:66 |
WT + DEL 8–48 transcripts |
nd |
nd |
nd |
|
C8 |
Asymptomatic |
Dup 1P-7 and dup 13–42 chrX:g. (33.068.711_33.068.771) _(32.684.693_32.684.750)dup; g.(32.523.766_32.523.826)_(32.228.415_32.228.475)dup |
73:27 (blood) 97:3 (sk.m.) |
Biallelic transcript (biallelic ex 21 SNP) |
nd |
nd |
nd |
|
C9 |
Asymptomatic |
Dup exon 2 c.32-?_93 + ?dup (out of frame) |
86:14 |
WT + DUP 2 transcripts |
74:26 |
36% (ex 12) 36% (ex 55) |
27% (ex 12) 27% (ex 55) |
|
C10 |
Asymptomatic |
Dup exons 3–44 c.94-?_6438 + ?dup (in frame) |
85:15 |
DUP 3–44 transcript (junction PCR) |
nd |
nd |
nd |
|
C11 |
Asymptomatic |
Del exons 48–52 c.6913-?_7660 + ?del (out of frame) |
23:77 |
WT + DEL 48–52 transcripts |
52:48 |
33% (ex 12) 48% (ex 55) |
17% (ex 12) 25% (ex 55) |
|
C12 |
Asymptomatic |
Del exons 46–51 c.6615-?_7542 + ?del (out of frame) |
65:35 |
WT + DEL 46–51 transcripts |
49:51 |
118% (ex 12) 128% (ex 55) |
58% (ex 12) 63% (ex 55) |
|
C13 |
Asymptomatic |
Del exons 49–50 c.7099-?_7309 + ?del (out of frame) |
44:56 |
WT + DEL 49–50 transcripts |
87:13 |
43% (ex 12) 34% (ex 55) |
38% (ex 12) 29% (ex 55) |
|
C14 |
Asymptomatic |
Del exon 52 c.7543-?_7660 + ?del (out of frame) |
87:13 |
WT + DEL 52 transcripts |
65:35 |
48% (ex 12) 92% (ex 55) |
31% (ex 12) 60% (ex 55) |
|
C15 |
Asymptomatic |
Del exons 50–79 c.7201-?_(*2691_?)del |
81:19 |
Biallelic transcript (biallelic ex 37 SNP) |
nd |
nd |
nd |
|
C16 |
Asymptomatic |
Del exons 44–79 chrX:g.(28.671.682_28.671.742)_(32.170.481_32.170.541)del |
53:47 |
Biallelic transcript (biallelic ex 21 SNP; monoallelic ex 37 SNP) |
nd |
nd |
nd |
|
C17 |
Asymptomatic |
c.1615C > T (ex 14) p.R539X |
42:58 |
WT + 1615C > T transcripts |
nd |
nd |
nd |
| C18 | Asymptomatic | c.10033C > T (ex 69) p.R3345X | 70:30 | WT + 10033C > T transcripts | nd | nd | nd |
Sk.m.: skeletal muscle; WT: wild-type; MUT: mutated; nd: not determined.
a The DNA mutation numbering is based on cDNA sequence with a “c.” symbol before the number with +1 corresponding to the A of the ATG translation initiation codon in the respective reference sequence (GenBank:M18533); in carriers C8 and C16 nucleotides are numbered according to March 2006 Human Reference Sequence, NCBI Build 36.1, hg18.