The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss
Abstract
:1. Introduction: Miscarriage and Genetics
2. Genetic Research into Pregnancy Loss: The Evolution of Methods
3. Next Generation Sequencing in the Analysis of Pregnancy Loss Genetics
4. A Systematic Review of Pregnancy Loss Genes
Gene (Locus) | Associated Diseases | Variant | Variant Origin † | Pregnancy Outcome | Reference |
---|---|---|---|---|---|
PADI6 chr1p36.13 | OMIM:617234 | NM_207421.4:c.1793A>G (p.Asn598Ser) NM_207421.4:c.2045G>A (p.Arg682Gln) | Inherited | Miscarriage | [55] |
NM_207421:c.122C>T (p.Ala41Val) | n.a. | Miscarriage | [49] | ||
STIL chr1p33 | OMIM:612703 | NM_001048166.1:c.1231C>G (p.His411Asp) NM_001048166.1:c.3370A>G (p.Met1124Val) | uncertain | Miscarriage | [65] |
NM_001048166:c. 1012C>T (p.His338Tyr) | Inherited | Miscarriage | [51] | ||
DYNC2H1 chr11q22.3 | OMIM:613091 | NM_001080463.1:c.2819-14A4G | Inherited | Termination | [46] |
NM_001080463.1:c.7577T4G (p. Ile2526Ser) | Inherited | Termination | [46] | ||
NM_001377.3:c.6047A>G (p.Tyr2016Cys) NM_001377.3:c.6551A>T (p.Asp2184Val) | Inherited | Miscarriage | [33] | ||
FGFR2 chr10q26.13 | 14 conditions | NM_000141:c.940-1G>A | n.a. | Fetal demise | [48] |
NM_022970.3:c.764G>A (p.Arg255Gln) | Inherited; | Neonatal death | [34] | ||
NM_022970.3:c.758C>G (p.Pro253Arg) | de novo | Termination | [34] | ||
FGFR3 chr4p16.3 | 14 conditions | NM_000142:c.1537G>T (p.Asp513Tyr) | n.a. | Miscarriage | [52] |
NM_000142:c.742C>T (p.Arg248Cys) | n.a. | Miscarriage | [52] | ||
NM_000142:c.1118A>G (p.Tyr373Cys) | n.a. | Termination | [26] | ||
FRAS1 chr4q21.21 | OMIM:219000 | NM_025074:c.8537C>A (p.Ala2846Asp) | Inherited | Miscarriage | [51] |
NM_025074.7:c.1918C>T (p.Arg640Cys) NM_025074.7:c.5205C>A (p.His1735Gln) | n.a. | Termination | [26] | ||
GREB1L chr18q11.1-q11.2 | OMIM:619274 | NM_001142966.2:c.5614dupA (p.Thr1872Asnfs*) | de novo | Termination | [34] |
OMIM:617805 | NM_001142966:c.1305dupA (p.Asp436Argfs*32) | n.a. | Miscarriage | [52] | |
LZTR1 chr22q11.21 | OMIM:616564 | ENST00000215739.8:c.902G>T (p.Gly301Val) | de novo | Termination | [34] |
OMIM:605275 | NM_006767:c.2317G>A (p.Val773Met) | n.a. | Miscarriage | [72] | |
PIEZO1 chr16q24.3 | OMIM:194380 | NM_001142864:c.1264C>T (p.Gln422Ter) | uncertain | Miscarriage | [72] |
OMIM:616843 | NM_001142864:c.2035G>T (p.Glu679X) | uncertain | Termination | [48] | |
NM_001142864.3:c.3206G>A (p.Trp1069Ter) NM_001142864.3:c.6208A>C (p.Lys2070Gln) | Inherited | Termination | [73] | ||
NM_001142864:c.30_31delAC (p.Leu10fs) | uncertain | Miscarriage | [51] | ||
PIK3R2 chr19p13.11 | OMIM:603387 | NM_005027:c.1117G>A (p.Gly373Arg) | n.a. | Fetal demise | [52] |
NM_005027:c.1690A>G (p.Lys564Glu) | n.a. | Miscarriage | [48] | ||
PTPN11 chr12q24.13 | 4 conditions | NM_002834:c.174C>A (p.Asn58Lys) | n.a. | Fetal demise | [48] |
NM_002834.4:c.218C>T (p.Thr73Ile) | de novo | Neonatal death | [34] | ||
COL2A1 chr12q13.11 | 15 conditions | NM_001844.5:c.3864_3865delCT (p.Cys1289Pfs*) | Inherited | Termination | [34] |
NM_001844.5:c.3490G>T (p.Gly1164Cys) | de novo | Miscarriage | [26] | ||
FOXP3 chrXp11.23 | OMIM:304790 | NM_014009.3:c.1009C>T (p.Arg337Ter) | Inherited | RPL | [74] |
NM_014009.3:c.906delT (p.Asp303fs*87) | Inherited | Fetal death | [75] | ||
NM_014009.3:c.1009C>T (p.Arg337X) | Inherited | Miscarriage | [76] | ||
NM_014009.3:c.1033C>T (p.Leu345Phe) | Inherited | Miscarriage | [77] | ||
NM_014009.3:c.1189CNT (p.Arg397Trp) | Inherited | Miscarriage | [78] | ||
NM_014009.3:c.319_320delTC | Inherited | Miscarriage | [78] | ||
NEB chr2q23.3 | OMIM:619334 | NM_001164507:c.20974delA (p.Val6993Serfs*8) | uncertain | Miscarriage | [72] |
OMIM:256030 | NM_001271208:c.24094C>T (p.Arg8032Ter) NM_001271208:c.20098C>A (p.Leu6700Ile) | uncertain | Miscarriage | [52] | |
RYR1 chr19q13.2 | 4 conditions | NM_000540.2:c.14130-2A>G NM_000540.2:c.9221C>T (p.Ser3074Phe) | Inherited | Termination | [46] |
NM_000540.2:c.6721C>T (p.Arg2241Ter) | Inherited | Miscarriage | [79] | ||
NM_000540.2:c.2097_2123del (p.Glu699_Gly707del) | Inherited | Termination | [79] | ||
NM_000540.2:c.7043delGA (p.Glu2347del) | Inherited | Termination | [79] | ||
RYR2 chr1q43 | OMIM:115000 OMIM:115000 | NM_001035.2:c.409C>T (p.Arg137Trp) NM_001035.2:c.4652A>G (p.Asn1551Ser) | Inherited | RPL | [39] |
NM_001035.2:c.12526G>A (p.Val4176Met) | Inherited | Stillbirth | [34] | ||
SCN5A chr3p22.2 | 9 conditions | NM_001160161:c.3749C>T (p.Thr1250Met) | Inherited | Miscarriage | [51] |
NM_198056:c.5393G>A (p.Trp1798Ter) | n.a. | Fetal demise | [52] | ||
NM_198056.3:c.1663G>T (p.Glu555Ter) | n.a. | Stillbirth | [50] | ||
NM_198056.3:c.1858C>T (p.Arg620Cys) | n.a. | Stillbirth | [50] | ||
NM_198056.3:c.5350G>A (p.Glu1784Lys) | n.a. | Stillbirth | [50] | ||
GBE1 chr3p12.2 | OMIM: 232500 OMIM:263570 | NM_000158:c.467G>A (p.Arg156His) NM_000158:c.-35_-54del | uncertain | Miscarriage | [51] |
NM_000158:c.1064G>A (p.Arg355His) | Inherited | Fetal demise | [47] | ||
NM_000158:c.1543C>T (p.Arg515Cys) | Inherited | Fetal demise | [47] |
5. Common Properties of Known Pregnancy Loss Genes
6. Construction of a List of Candidate Pregnancy Loss Genes
7. Conclusions
Supplementary Materials
Author Contributions
Funding
Institutional Review Board Statement
Informed Consent Statement
Data Availability Statement
Conflicts of Interest
Abbreviations
gnomAD | genome aggregation database |
pLI | probability of loss-of-function intolerance |
pLoF | putative loss-of-function variants |
ACMG | American College of Medical Genetics and Genomics |
GO | gene ontology |
GTEx | genotype tissue expression |
LOEUF | loss-of-function observed-to-expected upper fraction |
MSigDB | molecular signatures database |
PL | pregnancy loss |
POC | product of conception |
RPL | recurrent pregnancy loss |
SA | spontaneous abortion |
TPM | transcripts per million |
VUS | variant of uncertain significance |
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Maksiutenko, E.M.; Barbitoff, Y.A.; Nasykhova, Y.A.; Pachuliia, O.V.; Lazareva, T.E.; Bespalova, O.N.; Glotov, A.S. The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss. Int. J. Mol. Sci. 2023, 24, 17572. https://doi.org/10.3390/ijms242417572
Maksiutenko EM, Barbitoff YA, Nasykhova YA, Pachuliia OV, Lazareva TE, Bespalova ON, Glotov AS. The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss. International Journal of Molecular Sciences. 2023; 24(24):17572. https://doi.org/10.3390/ijms242417572
Chicago/Turabian StyleMaksiutenko, Evgeniia M., Yury A. Barbitoff, Yulia A. Nasykhova, Olga V. Pachuliia, Tatyana E. Lazareva, Olesya N. Bespalova, and Andrey S. Glotov. 2023. "The Landscape of Point Mutations in Human Protein Coding Genes Leading to Pregnancy Loss" International Journal of Molecular Sciences 24, no. 24: 17572. https://doi.org/10.3390/ijms242417572