Table 1. Summary of patients affected with progeroid syndromes carrying pathogenic ZMPSTE24 mutations.
| Patients | Mutations (allele 1; allele 2) | Position | Protein prediction | Protein function | Prelamin A accumulation | Reference |
|---|---|---|---|---|---|---|
| Restrictive dermopathy | ||||||
| RD—family 1 | c.50delA; c.1085dupT | Exon1; exon 9 | p.Lys17Serfs*21/p.Leu362Phefs*19 | NA | NA | Present report and Smigiel et al20 |
| RD—family 2 (consanguineous Turkish) | c.209_210delAT; c.209_210delAT | Exon 2 | p.Tyr70Serfs*4 | NA | NA | Present report |
| RD—family 3 | c.54dupT; c.826 C>T | Exon 1; exon 7 | p.Ile19Tyrfs*28/p.Arg276* | NA | NA | Present report and Moulson et al14 |
| RD—family 4 (consanguineous German) | c.1105C>T; c.1105C>T | Exon 9 | p.Arg369* | NA | NA | Present report |
| RD—family 5 | c.475-2A>G; c.628-2A>G | Intron 4; intron 5 | p.Thr159_Leu209del/p.Val210Aspfs*21 | NA | NA | Present report |
| RD—family 6 | c.954+2 T>A; c.1085dupT | Intron 7; exon 9 | p.Gly256Glufs*2/p.Leu362Phefs*19 | NA | NA | Present report |
| Nine additional RD—families | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362fs*19 | NA | NA | Present report |
| Patient P2 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362PhefsX19 | Null | Complete | Navarro et al3 (patient P2) |
| Patient P3 | c.1085dupT; r.271_627del | Exon 9; exon 3-5del | p.Leu362Phefs*19/p.Leu91_Leu209del | Null | Complete | Navarro et al3 (P3) |
| Patient P5 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | Null | Complete | Navarro et al3 (P5) |
| Patient P6 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | Null | Complete | Navarro et al3 (P6) |
| Patient P7 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | Null | Complete | Navarro et al3 (P7) |
| Patient P8 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Navarro et al3 (P8) |
| Patient P9 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Navarro et al3 (P9) |
| Patient P10 | c.1085dupT; c.1249C>T | Exon 9; exon 10 | p.Leu362Phefs*19/p.Gln417* | NA | NA | Navarro et al3 (P10) |
| Patient P11 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Navarro et al3 (P11) |
| Patient P12 | c.1085dupT; c.295delC | Exon 9 | p.Leu362Phefs*19/p.Pro99Leufs*38 | NA | NA | Navarro et al3 (P12) |
| Consanguineous Dutch family | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Moulson et al14 |
| American family | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | Null | Complete | Moulson et al14 |
| Consanguineous Guatemalan family | c.591dupT; c.591dupT | Exon 5 | p.Ile198fs*19 | Null | Complete | Moulson et al14 |
| Mennonite kindred | c.54dupT; c.54dupT | Exon 1 | p.Ile19Tyrfs*28 | NA | NA | Moulson et al14 |
| Isolated Dutch case | c.1085dupT; c.591dupT | Exon 9 | p.Leu362Phefs*19/p.Ile198fs*19 | NA | NA | Moulson et al14 |
| Case report—Iranian patient | c.627 +1G>C; c.627 +1G>C | Intron 5 | p.Thr159_Leu209del | Null | Presence | Sander et al16 |
| Case report | c.1385C>T;? | Exon 10 | p.Leu462Arg/? | NA | NA | Thill et al17 |
| Chinese patient | c.715G>T; c.715G>T | Exon 6 | p.Glu239* | NA | NA | Chen et al15 |
| Case report 1 | c.691G>T; c.691G>T; | Exon 6 | p.Glu231* | NA | NA | Jagadeesh et al19 |
| Case report 2 | c.691G>T; c.691G>T; | Exon 6 | p.Glu231* | NA | NA | Jagadeesh et al19 |
| Case report Iranian | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Kariminejad et al44 |
| Caucasian case report | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Morais et al45 |
| Case report Mennonite Kindred | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Li et al46 |
| RD-600 | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Ahmad et al18, 23 |
| RD-500—consanguineous Mexican family | c.1020G>A; c.1020G>A | Exon 8 | p.Trp340* | NA | NA | Ahmad et al18, 23 |
| Two affected sibling | c.50delA; c.584_585delAT | Exon1; exon 5 | p.Lys17Serfs*21/p.Tyr195Phefs*22 | NA | NA | Smigiel et al20 |
| Case report Turkish | c.1085dupT; c.1085dupT | Exon 9 | p.Leu362Phefs*19 | NA | NA | Yesil et al47 |
| Two sibling | c.715G>T; c.715G>T | Exon 6 | p.Glu239* | NA | NA | Lu et al21 |
| Mandibuloacral dyslplasia (MAD-type B) and other progeroïde syndromes | ||||||
| MAD-B—Family 7 (Turkish) | c.1204-1G>A; c.794A>G | Intron 9; exon 7 | p.Val402Phefs*6; p.Asn265Ser | present report | ||
| MAD-B (MAD600) | c.1085dupT; c.1018T>C | Exon 9; exon 8 | p.Leu362Phefs*19/p.Trp340Arg | Null/residual activity | NA | Agarwal et al13 |
| HGPS/MAD | c.1085dupT; c.794A>G | Exon 9; exon 7 | p.Leu362Phefs*19/p.Asn265Ser | Null/residual activity | Partial | Shackleton et al28 |
| Australian HGPS/MAD | c.1085dupT; c.794A>G | Exon 9; exon 7 | p.Leu362Phefs*19/p.Asn265Ser | NA | NA | Agarwal et al22 |
| HGPS/MAD | c.1204_1225del22; c.1204_1225del22a | Exon 10 | p.Val402Serfs*1 | Null | Complete b | Denecke et al26 |
| Severe MAD—two affected sister | c.121C>T; c.743C>T | Exon 1; Exon 6 | p.Gln41*/p.Pro248Leu | Null/residual activity | Partial | Miyoshi et al27 |
| Early onset MAD—(MAD4700) | c.743C>T; c.1349G>A | Exon 6; exon 10 | p.Pro248Leu/p.Trp450* | NA | NA | Ahmad et al18, 23 |
| MAD—with severe skeletal phenotype | c.794A>G; c.207_208delCT | Exon 7; exon 2 | p.Asn256Ser/p.Tyr70Serfs*4 | NA | NA | Cunningham et al25 |
| MAD-B with muscular defects—case report | c.281T>C; c.281T>C | Exon 3 | Leu94Pro/Leu94Pro | Residual | Partial | Ben Yaou et al24 |
Abbreviation: NA, non available.
Patients previously described and reported here (shown in italic) and their associated mutations are detailed and resumed according to their phenotypic features.
a
ZMPSTE24 mutations associated with a heterozygous LMNA mutation, p.R654*.
b
One part of the (pre)lamin A pool, is not farnesylated because of the presence of the p.R654* mutation.