| Disease . | PKD . | FRDA . | GAA-FGF14-related ataxia . | XDP . | CANVAS . | RCC . | Follicular lymphoma . | Burkitt lymphoma . | Diffuse large B cell lynphoma . |
|---|---|---|---|---|---|---|---|---|---|
| Year of genetic discovery | 1995 (181) | 1996 (202) | 2023 (249,250) | 2017 (268) | 2019 (284,285) | 2022 (160) | 2004 (316) | 1993 (319) | 2024 (324) |
| H-motif | 2.5 kb-long PyRE with 23 perfect and 4 imperfect mirror repeats (179) | (GAA)n (202) | (GAA)n (249,250) | (CCCTCT)n (268) | (AAGGG)n (284,285) | (GAAA)n (160) | 150 Mbr (317) | 5′-GGGAGGGGCGCTTATGGGGAGGG-3′ (177) | 5′-TGGAAAGGAGGTGGAGGAGAGGAA-3′ (211) |
| Evidence for H-DNA formation | In vitro (71,77,182) | In vitro (69,114,217–220) In vivo (159) | Unknown within context of this disease | Unknown | In vitro(300) | Unknown | In vitro (316,317) | In vitro (94,176,320) | In vitro (324) |
| H-motif location | Intron 21 of PKD1 gene gene (166,179,180) | First intron of FXN gene (202) | First intron of FGF14 gene (249,250) | 2.6 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in 32nd intron of TAF1 gene (268,276,333) | Poly(A) tail of AluSx3 element in second intron of RFC1 gene (284,285) | First intron of UGT2B7 gene (160) | Mbr of BCL2 gene (317) | Promoter region of c-myc gene (319) | Cluster II region of 5′ UTR of BCL6 (324) |
| Nonpathogenic/ pathogenic alleles | N/A | Unaffected:(GAA)33; Carriers: (GAA)34–66; Affected: (GAA)>66 (202,211–213) | Unaffected:(GAA)<25, (GAAGGA)n, ((GAA)4(GCA))n; Partially penetrant: (GAA)>250; Fully penetrant: (GAA)>300 (249,250,261) | Unaffected:absence of insertion; Affected: (CCCTCT)30–55 (268,276,333) | Unaffected:(AAAAG)n, (AAGAG)n, (AGAGG)n, (AAAGG)<200; Affected: (AAGGG)>400, (ACAGG)n, (AAAGG)>700; Many other iterations with unknown pathogenicity (284,285,287,289–293,296) | Unaffected: (GAAA)∼26; Affected: (GAAA)63–160 (160) | N/A | N/A | N/A |
| Inheritance pattern | Autosomal dominant (178) | Autosomal recessive (202) | Autosomal dominant (249,250) | Autosomal recessive (262,334) | Autosomal recessive (284) | Unknown | N/A | N/A | N/A |
| Pathogenic mechanism | Mutations in PKD1 gene→kidney cysts→End-stage renal disease (178) | (GAA)exp→epigenetic gene silencing→loss of function (114,123,238,239) | Unknown,haploinsufficiency suggested (249,250) | Loss of function (RNA and protein); intron retention (269,277,278,335) | Unknown, loss of function suspected (284,287,303–306) | Unknown | RAG complex-mediated H-DNA cleavage→DSB→ translocation between BCL2 and immunoglobulin heavy-chain (316,317) | Translocation between c-myc and an immunoglobulin gene→constitutive c-myc expression | Translocation between BCL6 and various translocation partners→constitutive BCL6 expression (324) |
| Interaction with cellular machinery | Stallsreplication (77,89) Interferes with transcription (187) | Stallsreplication; replication-related mechanisms of repeat instability (85,88,90,91,223,224) Interferes with transcription (69,82,241,242) Instability related to BER and MMR pathways (85,108,109,226–229) | Unknown within context of this disease | MMR machinery modify instability (270) | Stalls replication (302) Reduces gene expression on protein level (302) | Unknown | RAG complex cleavage of H-DNA structure (317) | NER protein binds H-motif (95) Triplex-mediated transcription arrest (321) | Unknown |
| Disease . | PKD . | FRDA . | GAA-FGF14-related ataxia . | XDP . | CANVAS . | RCC . | Follicular lymphoma . | Burkitt lymphoma . | Diffuse large B cell lynphoma . |
|---|---|---|---|---|---|---|---|---|---|
| Year of genetic discovery | 1995 (181) | 1996 (202) | 2023 (249,250) | 2017 (268) | 2019 (284,285) | 2022 (160) | 2004 (316) | 1993 (319) | 2024 (324) |
| H-motif | 2.5 kb-long PyRE with 23 perfect and 4 imperfect mirror repeats (179) | (GAA)n (202) | (GAA)n (249,250) | (CCCTCT)n (268) | (AAGGG)n (284,285) | (GAAA)n (160) | 150 Mbr (317) | 5′-GGGAGGGGCGCTTATGGGGAGGG-3′ (177) | 5′-TGGAAAGGAGGTGGAGGAGAGGAA-3′ (211) |
| Evidence for H-DNA formation | In vitro (71,77,182) | In vitro (69,114,217–220) In vivo (159) | Unknown within context of this disease | Unknown | In vitro(300) | Unknown | In vitro (316,317) | In vitro (94,176,320) | In vitro (324) |
| H-motif location | Intron 21 of PKD1 gene gene (166,179,180) | First intron of FXN gene (202) | First intron of FGF14 gene (249,250) | 2.6 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in 32nd intron of TAF1 gene (268,276,333) | Poly(A) tail of AluSx3 element in second intron of RFC1 gene (284,285) | First intron of UGT2B7 gene (160) | Mbr of BCL2 gene (317) | Promoter region of c-myc gene (319) | Cluster II region of 5′ UTR of BCL6 (324) |
| Nonpathogenic/ pathogenic alleles | N/A | Unaffected:(GAA)33; Carriers: (GAA)34–66; Affected: (GAA)>66 (202,211–213) | Unaffected:(GAA)<25, (GAAGGA)n, ((GAA)4(GCA))n; Partially penetrant: (GAA)>250; Fully penetrant: (GAA)>300 (249,250,261) | Unaffected:absence of insertion; Affected: (CCCTCT)30–55 (268,276,333) | Unaffected:(AAAAG)n, (AAGAG)n, (AGAGG)n, (AAAGG)<200; Affected: (AAGGG)>400, (ACAGG)n, (AAAGG)>700; Many other iterations with unknown pathogenicity (284,285,287,289–293,296) | Unaffected: (GAAA)∼26; Affected: (GAAA)63–160 (160) | N/A | N/A | N/A |
| Inheritance pattern | Autosomal dominant (178) | Autosomal recessive (202) | Autosomal dominant (249,250) | Autosomal recessive (262,334) | Autosomal recessive (284) | Unknown | N/A | N/A | N/A |
| Pathogenic mechanism | Mutations in PKD1 gene→kidney cysts→End-stage renal disease (178) | (GAA)exp→epigenetic gene silencing→loss of function (114,123,238,239) | Unknown,haploinsufficiency suggested (249,250) | Loss of function (RNA and protein); intron retention (269,277,278,335) | Unknown, loss of function suspected (284,287,303–306) | Unknown | RAG complex-mediated H-DNA cleavage→DSB→ translocation between BCL2 and immunoglobulin heavy-chain (316,317) | Translocation between c-myc and an immunoglobulin gene→constitutive c-myc expression | Translocation between BCL6 and various translocation partners→constitutive BCL6 expression (324) |
| Interaction with cellular machinery | Stallsreplication (77,89) Interferes with transcription (187) | Stallsreplication; replication-related mechanisms of repeat instability (85,88,90,91,223,224) Interferes with transcription (69,82,241,242) Instability related to BER and MMR pathways (85,108,109,226–229) | Unknown within context of this disease | MMR machinery modify instability (270) | Stalls replication (302) Reduces gene expression on protein level (302) | Unknown | RAG complex cleavage of H-DNA structure (317) | NER protein binds H-motif (95) Triplex-mediated transcription arrest (321) | Unknown |
This table enumerates the year of genetic discovery of the disease, H-motif involved in each disease, evidence for H-DNA formation, where the H-motif resides, the known nonpathogenic and pathogenic alleles, inheritance pattern, the pathogenic mechanism known or hypothesized, and interaction of the H-motif with cellular machinery.
| Disease . | PKD . | FRDA . | GAA-FGF14-related ataxia . | XDP . | CANVAS . | RCC . | Follicular lymphoma . | Burkitt lymphoma . | Diffuse large B cell lynphoma . |
|---|---|---|---|---|---|---|---|---|---|
| Year of genetic discovery | 1995 (181) | 1996 (202) | 2023 (249,250) | 2017 (268) | 2019 (284,285) | 2022 (160) | 2004 (316) | 1993 (319) | 2024 (324) |
| H-motif | 2.5 kb-long PyRE with 23 perfect and 4 imperfect mirror repeats (179) | (GAA)n (202) | (GAA)n (249,250) | (CCCTCT)n (268) | (AAGGG)n (284,285) | (GAAA)n (160) | 150 Mbr (317) | 5′-GGGAGGGGCGCTTATGGGGAGGG-3′ (177) | 5′-TGGAAAGGAGGTGGAGGAGAGGAA-3′ (211) |
| Evidence for H-DNA formation | In vitro (71,77,182) | In vitro (69,114,217–220) In vivo (159) | Unknown within context of this disease | Unknown | In vitro(300) | Unknown | In vitro (316,317) | In vitro (94,176,320) | In vitro (324) |
| H-motif location | Intron 21 of PKD1 gene gene (166,179,180) | First intron of FXN gene (202) | First intron of FGF14 gene (249,250) | 2.6 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in 32nd intron of TAF1 gene (268,276,333) | Poly(A) tail of AluSx3 element in second intron of RFC1 gene (284,285) | First intron of UGT2B7 gene (160) | Mbr of BCL2 gene (317) | Promoter region of c-myc gene (319) | Cluster II region of 5′ UTR of BCL6 (324) |
| Nonpathogenic/ pathogenic alleles | N/A | Unaffected:(GAA)33; Carriers: (GAA)34–66; Affected: (GAA)>66 (202,211–213) | Unaffected:(GAA)<25, (GAAGGA)n, ((GAA)4(GCA))n; Partially penetrant: (GAA)>250; Fully penetrant: (GAA)>300 (249,250,261) | Unaffected:absence of insertion; Affected: (CCCTCT)30–55 (268,276,333) | Unaffected:(AAAAG)n, (AAGAG)n, (AGAGG)n, (AAAGG)<200; Affected: (AAGGG)>400, (ACAGG)n, (AAAGG)>700; Many other iterations with unknown pathogenicity (284,285,287,289–293,296) | Unaffected: (GAAA)∼26; Affected: (GAAA)63–160 (160) | N/A | N/A | N/A |
| Inheritance pattern | Autosomal dominant (178) | Autosomal recessive (202) | Autosomal dominant (249,250) | Autosomal recessive (262,334) | Autosomal recessive (284) | Unknown | N/A | N/A | N/A |
| Pathogenic mechanism | Mutations in PKD1 gene→kidney cysts→End-stage renal disease (178) | (GAA)exp→epigenetic gene silencing→loss of function (114,123,238,239) | Unknown,haploinsufficiency suggested (249,250) | Loss of function (RNA and protein); intron retention (269,277,278,335) | Unknown, loss of function suspected (284,287,303–306) | Unknown | RAG complex-mediated H-DNA cleavage→DSB→ translocation between BCL2 and immunoglobulin heavy-chain (316,317) | Translocation between c-myc and an immunoglobulin gene→constitutive c-myc expression | Translocation between BCL6 and various translocation partners→constitutive BCL6 expression (324) |
| Interaction with cellular machinery | Stallsreplication (77,89) Interferes with transcription (187) | Stallsreplication; replication-related mechanisms of repeat instability (85,88,90,91,223,224) Interferes with transcription (69,82,241,242) Instability related to BER and MMR pathways (85,108,109,226–229) | Unknown within context of this disease | MMR machinery modify instability (270) | Stalls replication (302) Reduces gene expression on protein level (302) | Unknown | RAG complex cleavage of H-DNA structure (317) | NER protein binds H-motif (95) Triplex-mediated transcription arrest (321) | Unknown |
| Disease . | PKD . | FRDA . | GAA-FGF14-related ataxia . | XDP . | CANVAS . | RCC . | Follicular lymphoma . | Burkitt lymphoma . | Diffuse large B cell lynphoma . |
|---|---|---|---|---|---|---|---|---|---|
| Year of genetic discovery | 1995 (181) | 1996 (202) | 2023 (249,250) | 2017 (268) | 2019 (284,285) | 2022 (160) | 2004 (316) | 1993 (319) | 2024 (324) |
| H-motif | 2.5 kb-long PyRE with 23 perfect and 4 imperfect mirror repeats (179) | (GAA)n (202) | (GAA)n (249,250) | (CCCTCT)n (268) | (AAGGG)n (284,285) | (GAAA)n (160) | 150 Mbr (317) | 5′-GGGAGGGGCGCTTATGGGGAGGG-3′ (177) | 5′-TGGAAAGGAGGTGGAGGAGAGGAA-3′ (211) |
| Evidence for H-DNA formation | In vitro (71,77,182) | In vitro (69,114,217–220) In vivo (159) | Unknown within context of this disease | Unknown | In vitro(300) | Unknown | In vitro (316,317) | In vitro (94,176,320) | In vitro (324) |
| H-motif location | Intron 21 of PKD1 gene gene (166,179,180) | First intron of FXN gene (202) | First intron of FGF14 gene (249,250) | 2.6 kb SINE-VNTR-Alu (SVA) retrotransposon insertion in 32nd intron of TAF1 gene (268,276,333) | Poly(A) tail of AluSx3 element in second intron of RFC1 gene (284,285) | First intron of UGT2B7 gene (160) | Mbr of BCL2 gene (317) | Promoter region of c-myc gene (319) | Cluster II region of 5′ UTR of BCL6 (324) |
| Nonpathogenic/ pathogenic alleles | N/A | Unaffected:(GAA)33; Carriers: (GAA)34–66; Affected: (GAA)>66 (202,211–213) | Unaffected:(GAA)<25, (GAAGGA)n, ((GAA)4(GCA))n; Partially penetrant: (GAA)>250; Fully penetrant: (GAA)>300 (249,250,261) | Unaffected:absence of insertion; Affected: (CCCTCT)30–55 (268,276,333) | Unaffected:(AAAAG)n, (AAGAG)n, (AGAGG)n, (AAAGG)<200; Affected: (AAGGG)>400, (ACAGG)n, (AAAGG)>700; Many other iterations with unknown pathogenicity (284,285,287,289–293,296) | Unaffected: (GAAA)∼26; Affected: (GAAA)63–160 (160) | N/A | N/A | N/A |
| Inheritance pattern | Autosomal dominant (178) | Autosomal recessive (202) | Autosomal dominant (249,250) | Autosomal recessive (262,334) | Autosomal recessive (284) | Unknown | N/A | N/A | N/A |
| Pathogenic mechanism | Mutations in PKD1 gene→kidney cysts→End-stage renal disease (178) | (GAA)exp→epigenetic gene silencing→loss of function (114,123,238,239) | Unknown,haploinsufficiency suggested (249,250) | Loss of function (RNA and protein); intron retention (269,277,278,335) | Unknown, loss of function suspected (284,287,303–306) | Unknown | RAG complex-mediated H-DNA cleavage→DSB→ translocation between BCL2 and immunoglobulin heavy-chain (316,317) | Translocation between c-myc and an immunoglobulin gene→constitutive c-myc expression | Translocation between BCL6 and various translocation partners→constitutive BCL6 expression (324) |
| Interaction with cellular machinery | Stallsreplication (77,89) Interferes with transcription (187) | Stallsreplication; replication-related mechanisms of repeat instability (85,88,90,91,223,224) Interferes with transcription (69,82,241,242) Instability related to BER and MMR pathways (85,108,109,226–229) | Unknown within context of this disease | MMR machinery modify instability (270) | Stalls replication (302) Reduces gene expression on protein level (302) | Unknown | RAG complex cleavage of H-DNA structure (317) | NER protein binds H-motif (95) Triplex-mediated transcription arrest (321) | Unknown |
This table enumerates the year of genetic discovery of the disease, H-motif involved in each disease, evidence for H-DNA formation, where the H-motif resides, the known nonpathogenic and pathogenic alleles, inheritance pattern, the pathogenic mechanism known or hypothesized, and interaction of the H-motif with cellular machinery.
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