From: First step towards a consensus strategy for multi-locus diagnostic testing of imprinting disorders
Laboratory | Aachen/DEa | Amsterdam/NL | Essen/DE | Madrid/ES | Milano/IT | Paris/FR | Salisbury/UK | Tokyo, Hamamatsu/JP | Vitoria-Gasteiz/ES | Total | ||
---|---|---|---|---|---|---|---|---|---|---|---|---|
First-line test | Molecular diagnosis | ME030/ME032 + ME034 | ME030/ME032 | ME030/ME032; ME034 for research | ME030/ME032 + ME034 + SNParray | ME030/ME032 | ASMM-RT qPCR (IC2, MEST, GRB10, MEG3, IG-DMR} | ME030/ME032 | MS- pyrosequencing (IC1, IC2, IG-DMR, PEG 10, MEST) | ME030/ME032;ME034 for research | Total number | ratio of molecular subgroups (resolved + unresolved) in the total cohort |
SRS | ||||||||||||
Referrals (total number) | 1164 | 546 | 287 | 348 | 586 | 876 | 388 | 455 | 71 | 4721 | ||
"Expected" molecular diagnoses | IC1 LOM | 158 | 36 | 27 | 44 | 62 | 97 | 27 | 113 | 8 | 572 | 67,6 |
11p15CNVs | 8 | 4 | 1 | 2 | 2 | NA | 1 | 2 | 0 | 20 | 2,4 | |
upd(11)mat | 0 | 0 | 0 | 3 | 0 | 0 | 1 | 1 | 0 | 5 | 0,6 | |
upd(7)mat | 37 | 3 | 5 | 9 | 17 | 21 | 10 | 31 | 1 | 134 | 15,8 | |
Sum "expected" diagnoses | 203 | 43 | 33 | 58 | 81 | 118 | 39 | 147 | 9 | 731 | ||
% "Expected" positive diagnoses | 17,4 | 7,9 | 11,5 | 16,7 | 13,8 | 13,5 | 8,2 | 32,3 | 12,7 | 15,5 | ||
Unexpected molecular diagnoses | IC2 LOM | 3 | 2 | 0 | 4 | 1 | 2 | 0 | 1 | 0 | 13 | 1,5 |
chromosome 7 alterations | 3 | 1 | 0 | 1 | 3 | 0 | 0 | 0 | 0 | 8 | 0,9 | |
14q32 alterationsb | 10 | 0 | 0 | 8 | 5 | 27 | 5 | 14 | 1 | 70 | 8,3 | |
upd(6)mat | 2 | NA | 0 | 2 | 1 | NA | NA | 2 | NA | 7 | 0,8 | |
upd(20)mat | 1 | NA | 0 | 0 | 3 | NA | NA | 6 | NA | 10 | 1,2 | |
PWS | 1 | NA | 0 | 0 | 0 | NA | NA | 2 | NA | 3 | 0,4 | |
upd(11)pat | 0 | 3 | 1 | 4 | 0,5 | |||||||
Sum "unexpected" diagnoses | 20 | 3 | 0 | 15 | 13 | 32 | 6 | 25 | 1 | 115 | ||
% total diagnostic yield (expected + unexpected) | 19,2 | 8,4 | 11,5 | 21,0 | 16,0 | 17,1 | 11,6 | 37,8 | 14,1 | 17,9 | ||
percentage of unexpected finding among the total findings | 9,0 | 6,5 | 0,0 | 20,5 | 13,8 | 21,3 | 13,3 | 14,5 | 10,0 | 13,6 | ||
MLIDc,d | 10 | 0 | NA | 0 | 14 | 0 | 3 | 2 | 29 | 5,1 |
First-line test*** | ME030 + ME034 | ME030 | ME030; ME034 for research | ME030 | ME030; ME034 for research | ASMM-RTqPCR (IC1/IC2/M EST, G RB10 /DLK 1/GTL2) | ME030 | MS-Pyrosequencing H19 IGF2, IG-DMR, PEG10, MEST) | ME030; ME034 if positive in ME030 | Total number | Ratio of molecular subgroups (resolved + unresolved) in the total cohort | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
BWS | ||||||||||||
Referrals (total number) | 475 | 756 | 400 | 679 | 1028 | 1258 | 269 | 169 | 66 | 5100 | ||
Expected molecular diagnoses | IC1 GOM | 16 | 16 | 10 | 4 | 17 | 73 | 1 | 15 | 1 | 153 | 11,8 |
IC2 LOM | 78 | 84 | 60 | 152 | 184 | 201 | 27 | 32 | 15 | 833 | 64,0 | |
CNVs 11p | 9 | 5 | 4 | 2 | 7 | 0 | 1 | 2 | 2 | 32 | 2,5 | |
upd(11)pat | 44 | 39 | 20 | 14 | 83 | 0 | 16 | 32 | 6 | 254 | 19,5 | |
Of these uniparental diploidyd | 4 | 2 | 1 | 2 | 0 | 1 | 1 | 0 | 11 | |||
Sum "expected" diagnoses | 147 | 144 | 94 | 172 | 291 | 274 | 45 | 81 | 24 | 1272 | ||
% "expected" positive diagnosee | 30,9 | 19,0 | 23,5 | 25,3 | 28,3 | 27,8 | 16,7 | 47,9 | 36,4 | 24,9 | ||
unexpected molecular diagnoses | IC1 LOM | 3 | 0 | 0 | 11 | 3 | 9 | 0 | 0 | 1 | 27 | 2,1 |
PHP | 0 | NA | NA | 0 | 0 | NA | NA | 2 | NA | 2 | 0,2 | |
Sum "unexpected" diagnoses | 3 | 0 | 0 | 11 | 3 | 9 | 0 | 2 | 1 | 29 | ||
% total diagnostic yield (expected + unexpected) | 31,6 | 19,0 | 23,5 | 27,0 | 28,6 | 22,5 | 16,7 | 49,1 | 37,9 | 25,5 | ||
Percentage of unexpected findings among the total findings | 2,0 | 0,0 | 0,0 | 6,0 | 1,0 | 3,2 | 0,0 | 2,4 | 4,0 | 2,2 | ||
MLIDcd | 21 | 3 | 3 | 20 | 25 | 22 | 3 | 2 | 8 | 107 | 12,8 |
Laboratory | Aachen/DE | Amsterdam/NL | Essen/DE | Madrid/ES | Milano/IT | Salisbury/UK | Tokyo, Hamamatsu/JP | Vitoria- Gasteiz/ES | Additional specialist laboratoriesf | Total number | ratio of molecular subgroups in the total cohort | |
---|---|---|---|---|---|---|---|---|---|---|---|---|
First-line test | Molecular diagnosis | disease-specific (MLPA) assays | ||||||||||
PWSg | ||||||||||||
Referrals (total number) | 33 | 344 | 825 | 218 | 420 | 400 | 260 | 87 | 420 | 3007 | ||
Molecular diagnoses | SNRPN ID | 4 | 0 | 32 | 2 | 13 | 1 | 9 | 1 | 2 | 64 | 10,0 |
del 15 pat | 6 | 20 | 59 | 9 | 22 | 15 | 18 | 3 | 100 | 252 | 39,4 | |
upd(15)mat | 1 | 7 | 48 | 13 | 20 | 10 | 49 | 10 | 0 | 158 | 24,7 | |
dup 15 mat | 0 | 3 | 6 | 8 | 18 | 2 | 29 | 66 | 10,3 | |||
upd(15)mat/ID unresolved | 0 | 2 | 32 | 0 | 26 | 5 | 35 | 0 | 0 | − 100 | 15,6 | |
total | 11 | 32 | 177 | 32 | 81 | 49 | 113 | 14 | 131 | 640 | ||
% positive diagnoses | 33,3 | 9,3 | 21,5 | 14,7 | 19,3 | 12,3 | 43,5 | 16,1 | 3f,2 | 21,3 | ||
ASg | ||||||||||||
Referrals (total number) | 17 | 103 | 631 | 131 | 630 | 165 | 49 | 87 | NA | 1813 | ||
Molecular diagnoses | SNRPN ID | 2 | 0 | 77 | 4 | 20 | 0 | 10 | 3 | 116 | 232 | 28,5 |
del 15 mat | 2 | 6 | 31 | 10 | 88 | 6 | 10 | 7 | 160 | 320 | 39,3 | |
upd(15)pat | 0 | 2 | 13 | 3 | 12 | 2 | 5 | 1 | 38 | 76 | 9,3 | |
dup 15 pat | 0 | 3 | 0 | 1 | 1 | 1 | 0 | 0 | 6 | 12 | 1,5 | |
UBE3Ah | NA | 3 | 3 | 1 | 52 | NA | 2 | 3 | 64 | 128 | 15,7 | |
upd(15)paVID unresolved | 0 | 4 | 0 | NA | 6 | 3 | 10 | 0 | 23 | 46 | 5,7 | |
total | 4 | 18 | 124 | 19 | 179 | 12 | 37 | 14 | 407 | 814 | ||
% positive diagnosesh | 23,5 | 17,5 | 19,7 | 14,5 | 28,4 | 7,3 | 75,5 | 16,1 | NA | NA | ||
TS14b,g | ||||||||||||
Referrals (total number) | 144 | 8 | 1 | 73 | 57 | 1 | 284 | |||||
Molecular diagnoses | upd(14)mat | NA | NA | 3 | 3 | 1 | 11 | 21 | 1 | NA | 40 | 48,8 |
del(14q32)pat | NA | NA | 1 | 1 | 0 | 1 | 6 | 0 | NA | 9 | 11.0 | |
ID | NA | NA | 9 | 0 | 0 | 3 | 13 | 0 | NA | 25 | 30,5 | |
upd(14)mat/ID unresolved | NA | NA | 1 | 0 | 0 | 2 | 5 | 0 | NA | 8 | 9,8 | |
total | 14 | 4 | 1 | 17 | 45 | 1 | 82 | |||||
% positive diagnoses | 9,7 | 50,0 | 100,0 | 23,3 | 78,9 | 100,0 | 28,9 | |||||
KOS14g | ||||||||||||
Referrals (total number) | NA | NA | 8 | 4 | 1 | 8 | 76 | 1 | NA | 98 | ||
Molecular diagnoses | upd(14)pat | NA | NA | 2 | 2 | 0 | 3 | 26 | 0 | NA | 33 | 46,5 |
del(14q32)mat | NA | NA | 2 | 0 | 1 | 1 | 9 | 1 | NA | 14 | 19,7 | |
ID | NA | NA | 1 | 0 | 0 | 1 | 15 | 0 | NA | 17 | 23,9 | |
upd(14)pat/ID unresolved | NA | NA | 0 | 0 | 0 | 3 | 4 | 0 | NA | 7 | 9,9 | |
total | 5 | 2 | 1 | 8 | 54 | 1 | 71 | |||||
% positive diagnoses | 62,5 | 50,0 | 100,0 | 100,0 | 71,1 | 100,0 | 72,4 | |||||
PHpg,h | ||||||||||||
Referrals (total number) | NA | NA | NA | 4 | 335 | 175 | 239 | NA | 753 | |||
Molecular diagnoses | upd(20)pat | NA | NA | NA | 1 | 4 | 0 | 7 | NA | 12 | 2,5 | |
del(20)mat | NA | NA | NA | 0 | 1 | 0 | 8 | NA | 9 | 1,9 | ||
ID | NA | NA | NA | 0 | 117 | 27 | 58 | NA | 202 | 42,6 | ||
upd(20)mat/ID unresolved | NA | NA | NA | 0 | 1 | 19 | NA | 20 | 4,2 | |||
STX16 del | NA | NA | NA | 0 | 34 | 36 | 19 | NA | 89 | 18,8 | ||
GNAS mutations | NA | NA | NA | 0 | 43 | 99 | NA | 142 | 30,0 | |||
total | 1 | 157 | 125 | 191 | 474 | |||||||
% positive diagnoses | 25,0 | 46,9 | 71,4 | 79,9 | 62,9 | |||||||
TNDMg | ||||||||||||
Referrals (total number) | NA | NA | 12 | 6 | NA | 272 | 6 | 1 | 291 | 588 | ||
Molecular diagnoses | upd(6)pat | NA | NA | 0 | 1 | NA | 44 | 2 | 1 | 22 | 70 | 34,0 |
dup(6)pat | NA | NA | 2 | NA | 23 | 1 | 0 | 26 | 52 | 25,2 | ||
ID | NA | NA | 0 | 2 | NA | 45 | 3 | 0 | 16 | 66 | 32,0 | |
of these, ZFP5T | NA | NA | NA | NA | NA | 17 | NA | NA | 7 | 24 | ||
upd(6)pat/ID unresolved | NA | NA | 0 | 0 | NA | 9 | 0 | 0 | 9 | 18 | 8,7 | |
total | 2 | 3 | 121 | 6 | 1 | 73 | 206 | |||||
% positive diagnoses | 16,7 | 50,0 | 44,5 | 100,0 | 100,0 | 25,1 | 35,0 |