Table 1 The formation and repair of DSBs mutations in POI patients

PRDM9

5p14.2

determines the positioning of the recombinant hotspots

c.229C > T, p. Arg77*

het

secondary

sporadic

[14]

c.638 T > G, p.Ile213Ser

het

secondary

sporadic

c.677A > T, p.Lys226Met

het

secondary

sporadic

ANKRD31

5q13.3

regulates the assembly of pre-DSB recombinsomes

c.1565-2A > G

het

splice site

secondary

sporadic

[14]

c.985C > T, p.Gln329*

het

nonsense

secondary

sporadic

NBN

8q21.3

participates in DNA end resection

c.871C > T, p.(Gln291*)

hom

nonsense

primary

sporadic

[52]

c.657_661del5

hom

Slavic founder

secondary

sporadic

[53]

HSF2BP

21q22.3

promotes homologous chromosomes synapsis and the formation of crossover

S167L

hom

missense

secondary

familial

[54]

c.382 T > C, p.C128R

hom

missense

secondary

sporadic

[55]

c.557 T > C, p.L186P

hom

missense

secondary

sporadic

EXO1

1q43

participates in DNA end resection

c.155C > G, p.Thr52Ser

het

missense

primary

sporadic

[56]

c.668G > A, p.Gly223Asp

het

missense

primary

sporadic

PSMC3IP

17q21.2

promotes the formation of nucleoprotein filament indirectly and strand exchange

c.496_497delCT, p.R166Afs

com het

Deletion

primary

sporadic

[57]

c.430_431insGA, p.L144*

Insertion

c.489 C > G, p.Tyr163Ter

hom

stop gain

familial

[58]

c.597 + 1G > T

com het

splicing

familial

[59]

c.268G > C, p.D90H

c.206_208delAGA, p.Lys69del

com het

deletion

familial

[60]

c.189 G > T, p.Lys63Asn

missense

familial

BRCA2

13q13.1

mediates the binding of recombinase RAD51 to ssDNA

c.7579delG, p.V2527X

com het

deletion

primary

familial

[61]

c.9693delA, p. S3231fs16*

deletion

c.8524C > T, p.R2842C

hom

missense

primary

familial

[62]

DMC1

22q13.1

binds ssDNA during meiosis

c.106G > A, p.Asp36Asn

hom

missense

secondary

familial

[63]

MEIOB

16p13.3

MEIOB-SPATA22 complexes can be recruited to DSB sites, promoting intact synapsis and the foramtion of crossover

c.1218G > A

hom

splicing

secondary

familial

[64]

c.683-1G > A

hom

splicing

secondary

familial

[65]

SPATA22

17p13.2

c.400C > T, p.R134X

hom

nonsense

normal

familial

[66]

c.900 + 1G > A

com het

splicing

secondary

sporadic

c.31C > T, p.R11X

SPIDR

8q11.21

promotes the formation of nucleoprotein filament

c.839G > A, p.W280*

hom

stop-gain

primary

familial

[67]

c.814C > T, R272*

hom

nonsense

primary

sporadic

[68]

MSH4

1p31.3

MSH4-MSH5 heterodimer can bind and stabilize the Holliday intermediates, promoting the formation of crossover

c.2355 + 1G > A

hom

donor splice-site

secondary

familial

[69]

c.2261C > T, p.Ser754Leu

hom

missense

secondary

familial

[70]

c.2198C > A, p.Ser733Ter

hom

stop-gain

secondary

sporadic

[71]

MSH5

6p21.33

c.1459G > T, p.D487Y

hom

missense

secondary

familial

[72]

c.1057C > A, p.L353M

het

secondary

sporadic

c.1459G > T, p.D487Y

het

secondary

sporadic

c.2107 A > G, p.I703V

het

secondary

sporadic

c.C1051G, p.R351G

het

missense

primary

sporadic

[73]

c.2063 T > C, p.I688T

com het

secondary

sporadic

[74]

c.604G > C, p.G202R

MCM8

20p12.3

MCM8-MCM9 hellicase complex participates in DNA end resection and promotes intermediates processing

c.446C > G, p.P149R

hom

missense

primary

familial

[75]

c.1954-1G > A

hom

splice

primary

familial

[76]

c.1469-1470insTA

hom

frameshift

primary

familial

c.464G > A, p.Cys155Tyr

het

primary

sporadic

[77]

c.548A > G, p.Asn183Ser

het

primary

sporadic

c.1334G > A, p.Arg445Gln

het

missense

primary

sporadic

c. A950T, p. H317L

het

missense

primary

sporadic

[78]

c. A1802G, p. H601R

het

missense

secondary

sporadic

c. 482A > C, p.His161Pro

hom

missense

primary

familial

[79]

c.89A > C, p.K30T

com het

familial

[80]

c.1330A > G, p.I444V

c.925C > T, p.R309*

hom

familial

c.925C > T, p.R309*

hom

nonsense

primary

familial

[81]

c.724 T > C, p.C242R

com het

missense

primary

familial

[82]

c.1334C > A, p.S445*

termination

c.351_354 delAAAG, p. K118Efs*5

hom

frameshift

primary

familial

[83]

MCM9

6q22.31

MCM8-MCM9 hellicase complex participates in DNA end resection and promotes intermediates processing

c.1732 + 2 T > C,

hom

splicing

primary

familial

[84]

c.394C > T, p.Arg132*

hom

insertion

primary

familial

c.397 T > C, p.Thr139Ala

het

secondary

sporadic

[77]

c.2422G > A, p.Val808Ile

het

missense

secondary

sporadic

c.1784C > G, p.Thr595Arg

het

missense

primary

sporadic

c.1651C > T, p.Gln551*

hom

stop gain

primary

sporadic

c.1483G > T, p.E495*

hom

nonsense

primary

familial

[85]

c.220C > T, p.R74*

hom

familial

[80]

c.1473dup, p.Thr492TyrfsTer4

hom

frameshift

familial

[86]

c.2059 T > C, p.F687L

com het

missense

primary

sporadic

[87]

c.3223C > T, p.P1075S

missense

c.1163C > A, p.T388N

het

secondary

sporadic

c.C1423T, p.L475F

het

missense

secondary

sporadic

[88]

c.T2921C, p.L974S

het

missense

secondary

sporadic

c.G3388A, p.A1130T

het

missense

secondary

sporadic

c.2488G > A, p.A830T

het

missense

secondary

sporadic

[89]

c.1157C > T, p.T386M

com het

secondary

sporadic

[74]

c.1291A > G, p.M431V

sporadic

HFM1

1p22.2

promotes homologous chromosomes synapsis and the formation of crossover

c.1686–1 G → C

com het

familial

[90]

c.2651 T → G, p.Ile884Ser

c.2206 G → A, p.Gly736Ser

com het

sporadic

c.3929_3930 delinsG, p.Pro1310Arg fs*41

frameshift

c.148G > A, p.Glu50Lys

het

missense

sporadic

[91]

c.1241A > C, p.His414Pro

het

missense

sporadic

c.2325C > A, p.Phe775Leu

het

missense

sporadic

c.3367 T > C, p.Ser1123Pro

het

missense

sporadic

c.3580C > T,p.Arg1194Cys

het

missense

sporadic

c.1686-1G > C

het

splice-site

sporadic

c.3470G > A

het

missense

secondary

familial

[91]

c.3100G > A, p.G1034S

com het

missense

secondary

sporadic

[92]

c.1006 + 1G > T

splice-site

ERCC6

10q11.23

promotes HR while suppresses NHEJ

c.C1769C > T, p. P590L

het

missense

secondary

sporadic

[74]

(CSB-PGBD3)

c.643G > T, p. E215X

het

nonsense

secondary

sporadic

[93]

c.3166G > A, p. V1056I

het

missense

secondary

sporadic

STAG3

7q22.1

maintains cohesin stability, ensures correct assemblage and segregation of homologous chromosomes

c.968delC, p.F187fs*7

hom

frameshift

primary

familial

[94]

c.1947_48dupCT, p.(Y650Sfs*22)

hom

duplication

primary

familial

[95]

c.1573 + 5G > A, p.Leu490Thrfs*10

hom

donor splice site

primary

familial

[96]

c.291dupC, p.Asn98Glnfs*2

com het

loss-of-function

primary

sporadic

[87, 97]

c.1950C > A, p.Tyr650*

loss-of-function

sporadic

c.3052delC, p.Arg1018Aspfs*14

com het

deletion

primary

familial

[98]

c.659 T > G, p.Leu220Arg

missense

familial

c.877_885del, p.293_295del

hom

in-frame

primary

familial

[99]

c.891_893dupTGA, p.297_298insAsp

hom

in-frame

primary

familial

c.962G A, p.Arg321His

hom

missense

primary

familial

[100]

c.962G > A, p.(Arg321His)

hom

missense

primary

sporadic

[101]

c.1336G > T, p.(Glu446Ter)

hom

nonsense

primary

familial

[102]

c.659 T > G, p.Leu220Arg

het

primary

sporadic

[103]

c.938A > T, p.Tyr313Phe

com het

primary

sporadic

c.1999C > T, p.Arg667Cys

primary

sporadic

c.2473C > G, p.Leu825Val

het

primary

sporadic

c.2612G > A, p.Arg871His

het

primary

sporadic

c.3381_3384delAGAA, p.Glu1128Metfs*42

hom

deletion

primary

sporadic

[104]

c.1942G > A, p. Ala648Thr

hom

missense

familial

[105]

c.1951_1953del, p. Leu652del

hom

in-frame deletion

familial

c.2773delT, p.Ser925Profs*6 del

hom

deletion

primary

sporadic

[106]

REC8

14q12

part of the cohesin complex

c.1035_1036dup p.Glu346Glyfs*72

Com het

frameshift

secondary

familial

[107]

c.624 + 1 G > A p.?

splicing

SMC1B

22q13.31

part of the cohesin complex

c.662 T > C, I221T

het

missense

secondary

sporadic

[108]

c.3530A > T, Q1177L

het

missense

primary

sporadic

C14orf39

14q23.1

part of the synaptonemal complex

c.204_205del, p.His68Glnfs*2

hom

frameshift

secondary

familial

[109]

c.508C > T, p.Arg170*

hom

nonsense

secondary

sporadic

[110]

SYCE1

10q26.3

part of the synaptonemal complex

c.613C > T, p.Gln205*

hom

nonsense

primary

familial

[111]

hom

deletion

secondary

familial

[112]

c.475G > A, p.Glu159Lys

com het

missense

secondary

sporadic

[110]

c.689_690del, p.Phe230Serfs*21

frameshift

NHEJ1

2q35

stabilizes and enhances the ligation activity of the XRCC4-LIG4 complex

c.532C > T, p.R178*

het

nonsense

secondary

familial

[113]

c.500A > G, p.Y167C

het

missense

secondary

sporadic