Category: All HBOC

LitAlert ~~ GeneLit.com

    • Genome-wide Analysis of Rare Haplotypes Associated with Breast Cancer Risk.
    • Wang F, Moon W, Letsou W, Sapkota Y, Wang Z, Im C, Baedke JL, Robison L, Yasui Y.
    • Cancer Res. 2022 Nov 10:CAN-22-1888. doi: 10.1158/0008-5472.CAN-22-1888. Epub ahead of print.

    • The Evolving Landscape of Pancreatic Cancer.
    • Krishnan M.
    • JCO Oncol Pract. 2022 Nov 10:OP2200636. doi: 10.1200/OP.22.00636. Epub ahead of print.

    • Genome- and transcriptome-wide association studies of 386,000 Asian and European-ancestry women provide new insights into breast cancer genetics.
    • Jia G, Ping J, Shu X, Yang Y, Cai Q, Kweon SS, Choi JY, Kubo M, Park SK, Bolla MK, Dennis J, Wang Q, Guo X, Li B, Tao R, Aronson KJ, Chan TL, Gao YT, Hartman M, Ho WK, Ito H, Iwasaki M, Iwata H, John EM, Kasuga Y, Kim MK, Kurian AW, Kwong A, Li J, Lophatananon A, Low SK, Mariapun S, Matsuda K, Matsuo K, Muir K, Noh DY, Park B, Park MH, Shen CY, Shin MH, Spinelli JJ, Takahashi A, Tseng C, Tsugane S, Wu AH, Yamaji T, Zheng Y, Dunning AM, Pharoah PDP, Teo SHKang D, Easton DF, Simard J, Shu X, Long J, Zheng W.
    • Am J Hum Genet. 2022 Nov 9:S0002-9297(22)00459-1. doi: 10.1016/j.ajhg.2022.10.011. Epub ahead of print.

    Related:

    •• Research news: Largest Genetic Risk Study in Breast Cancer Reveals Differences Between Asian and European Populations. (Inside Precision Medicine)

    • Study Suggests a PARP Inhibitors Has Wider Cancer Applications.
    • [No author given]
    • Inside Precision Medicine. Topics. Oncology. 2022 Nov 9.

    Related:

    •• Original research:

    A phase II study of talazoparib monotherapy in patients with wild-type BRCA1 and BRCA2 with a mutation in other homologous recombination genes.

    • Genomic and transcriptomic profiling indicates the prognosis significance of mutational signature for TMB-high subtype in Chinese patients with gastric cancer.
    • Cheng Y, Bu D, Zhang Q, Sun R, Lyle S, Zhao G, Dong L, Li H, Zhao Y, Yu J, Hao X.
    • J Adv Res. 2022 Nov 6:S2090-1232(22)00248-X. doi: 10.1016/j.jare.2022.10.019. Epub ahead of print.

    • From the patient to the population: Use of genomics for population screening.
    • Mighton C, Shickh S, Aguda V, Krishnapillai S, Adi-Wauran E, Bombard Y.
    • Front Genet. 2022 Oct 24;13:893832. doi: 10.3389/fgene.2022.893832.

    • LitAlert ~~ GeneLit.com

    • Reproductive risk factors associated with breast cancer in young women by molecular subtype.
    • Ruddy KJ, Vierkant RA, Jahan N, Higgins A, Partridge A, Larson N, Radisky DC, Couch F, Olson J, Sherman ME.
    • Breast. 2022 Nov 9:S0960-9776(22)00187-4. doi: 10.1016/j.breast.2022.11.004. Epub ahead of print.

    • Using a machine learning algorithm to predict outcome of primary cytoreductive surgery in advanced ovarian cancer.
    • Piedimonte S, Erdman L, So D, Bernardini MQ, Ferguson SE, Laframboise S, Bouchard Fortier G, Cybulska P, May T, Hogen L.
    • J Surg Oncol. 2022 Nov 9. doi: 10.1002/jso.27137. Epub ahead of print.

    • Rucaparib in recurrent ovarian cancer: real-world experience from the rucaparib early access programme in Spain - A GEICO study.
    • Yubero A, Barquín A, Estévez P, Pajares B, Sánchez L, Reche P, Alarcón J, Calzas J, Gaba L, Fuentes J, Santaballa A, Salvador C, Manso L, Herrero A, Taus Á, Márquez R, Madani J, Merino M, Marquina G, Casado V, Constenla M, Gutiérrez M, Dosil A, González-Martín A.
    • BMC Cancer. 2022 Nov 8;22(1):1150. doi: 10.1186/s12885-022-10191-5.

    • NBN pathogenic germline variants are associated with pan-cancer susceptibility and in vitro DNA damage response defects.
    • Belhadj S, Khurram A, Bandlamudi C, Palou-Márquez G, Ravichandran V, Steinsnyder Z, Wildman T, Catchings A, Kemel Y, Mukherjee S, Fesko B, Arora K, Mehine M, Dandiker S, Izhar A, Petrini J, Domchek S, Nathanson KL, Brower J, Couch F, Stadler Z, Robson M, Walsh M, Vijai J, Berger M, Supek F, Karam R, Topka S, Offit K.
    • Clin Cancer Res. 2022 Nov 8:CCR-22-1703. doi: 10.1158/1078-0432.CCR-22-1703. Epub ahead of print.

    • Resistance to Poly (ADP-Ribose) Polymerase Inhibitors (PARPi): Mechanisms and Potential to Reverse.
    • Washington CR, Moore KN.
    • Curr Oncol Rep. 2022 Nov 8. doi: 10.1007/s11912-022-01337-6. Epub ahead of print.
    • Review

    • Study: More is not better: PARP dose can be safely reduced for people with ovarian cancer.
    • [No author given]
    • FORCE. XRAY. 2022 Nov 8.

    Related:

    •• Original research:

    The impact of olaparib dose reduction and treatment interruption on treatment outcome in the SOLO2/ENGOT-ov21 platinum-sensitive recurrent ovarian cancer.

    • Tests to Guide PARP Inhibitors Emerge as New Focus for Public-Private Harmonization Effort.
    • Ashford K.
    • Precision Oncology News. 2022 Nov 8.
    • News

    • LitAlert ~~ GeneLit.com

    • The prevalence of germline pathogenic variants in Estonian colorectal cancer patients: results from routine clinical setting 2016–2021.
    • Roht L, Tooming M, Rekker K, Roomere H, Toome K, Murumets Ü, Šamarina U, Õunap K, Kahre T.
    • Front Genet. 2022 Nov 8;12:1020543. doi: 10.3389/fgene.2022.1020543.

    • Implementation of multigene panel testing for breast and ovarian cancer in South Africa: a step towards excellence in Oncology for the public sector.
    • Van Der Merwe NC, Ntaita KS, Stofberg H, Combrink HM, Oosthuizen J, Kotze MJ.
    • Front Oncol. 2022 Nov 8;12:938561. doi: 10.3389/fonc.2022.938561.

    • Society of Gynecologic Oncology Journal Club: Controversial Conversations in Gynecologic Cancer - Navigating Maintenance Therapy for Homologous Recombinant Proficient Ovarian Cancer.
    • Goldsberry WN, Norquist BS, Rocconi RP, Modesitt SC, Urban RR.
    • Gynecol Oncol Rep. 2022 Nov 8;101103. doi: 10.1016/j.gore.2022.101103.

    • Germline Pathogenic Variants Associated with Ovarian Cancer: A Historical Overview.
    • Lund Johansen E, Fribert Thusgaard C, Thomassen M, Eriksen Boonen S, Jochumsen KM.
    • Gynecol Oncol Rep. 2022 Nov 8;101105. doi: 10.1016/j.gore.2022.101105.

    • A genome-wide association study of mammographic texture variation.
    • Liu Y, Chen H, Heine J, Lindstrom S, Turman C, Warner ET, Winham SJ, Vachon CM, Tamimi RM, Kraft P, Jiang X.
    • Breast Cancer Res. 2022 Nov 7;24(1):76. doi: 10.1186/s13058-022-01570-8.

    • Lack of impact of the ALDH2 rs671 variant on breast cancer development in Japanese BRCA1/2-mutation carriers.
    • Mori T, Okamoto Y, Mu A, Ide Y, Yoshimura A, Senda N, Inagaki-Kawata Y, Kawashima M, Kitao H, Tokunaga E, Miyoshi Y, Ohsumi S, Tsugawa K, Ohta T, Katagiri T, Ohtsuru S, Koike K, Ogawa S, Toi M, Iwata H, Nakamura S, Matsuo K, Takata M.
    • Cancer Med. 2022 Nov 7. doi: 10.1002/cam4.5430. Epub ahead of print.

    • Cost-effectiveness of poly-(ADP-ribose) polymerase (PARP)-inhibitors for the maintenance treatment after responding to first- and second-line chemotherapy in advanced ovarian cancer.
    • Giuliani J, Mantoan B, Ferrario L, Candela MV, Aprile G.
    • J Oncol Pharm Pract. 2022 Nov 7:10781552221137705. doi: 10.1177/10781552221137705. Epub ahead of print.

    • Sister chromatid exchanges induced by perturbed replication can form independently of BRCA1, BRCA2 and RAD51.
    • Heijink AM, Stok C, Porubsky D, Manolika EM, de Kanter JK, Kok YP, Everts M, de Boer HR, Audrey A, Bakker FJ, Wierenga E, Tijsterman M, Guryev V, Spierings DCJ, Knipscheer P, van Boxtel R, Ray Chaudhuri A, Lansdorp PM, van Vugt MATM.
    • Nat Commun. 2022 Nov 7;13(1):6722. doi: 10.1038/s41467-022-34519-8.

    • Analysis of matched primary and recurrent BRCA1/2 mutation-associated tumors identifies recurrence-specific drivers.
    • Shah JB, Pueschl D, Wubbenhorst B, Fan M, Pluta J, D'Andrea K, Hubert AP, Shilan JS, Zhou W, Kraya AA, Llop Guevara A, Ruan C, Serra V, Balmaña J, Feldman M, Morin PJ, Nayak A, Maxwell KN, Domchek SM, Nathanson KL.
    • Nat Commun. 2022 Nov 7;13(1):6728. doi: 10.1038/s41467-022-34523-y.

    • A case of metastatic treatment-emergent small cell/neuroendocrine prostate cancer with BRCA2 mutation diagnosed by liver biopsy.
    • Naiki T, Naiki-Ito A, Kawai T, Komatsu H, Nishikawa R, Gonda M, Aoki M, Sugiyama Y, Tasaki Y, Yasui T.
    • IJU Case Rep. 2022 Jun 29 [eCollection 2022 Nov];5(6):431-435. doi: 10.1002/iju5.12501.

    Related:

    •• Commentary:

    Editorial Comment from Dr Sekino and Dr Hinata to A case of metastatic treatment emergent small cell/neuroendocrine prostate cancer with BRCA2 mutation diagnosed by liver biopsy.

    •• Commentary:

    Editorial Comment from Dr Kato to A case of metastatic treatment-emergent small cell/neuroendocrine prostate cancer with BRCA2 mutation by liver biopsy.

    • Prostate cancer recurring as small-cell carcinoma with a BRCA2 somatic mutation.
    • Yabusaki R, Yoshimura K, Taku K, Suzuki M.
    • IJU Case Rep. 2022 Aug 12 [eCollection 2022 Nov];5(6):489-492. doi: 10.1002/iju5.12523.

    • LitAlert ~~ GeneLit.com

    • Overview of familial syndromes with increased skin malignancies.
    • Juan HY, Zhou AE, Hoegler KM, Khachemoune A.
    • Arch Dermatol Res. 2022 Nov 7. doi: 10.1007/s00403-022-02447-8. Epub ahead of print.
    • Review

    • Thermo Fisher Introduces Homologous Recombination Deficiency Score for Cancer Profiling Assay.
    • Han AP.
    • GenomeWeb. 2022 Nov 7.
    • News

    • Loss of Heterozygosity of BRCA1/2 as a Predictive Marker for Talazoparib Response.
    • Mizrahi AG, Hamad H, Gugenheim A, Nisman B, Kuznetz A, David IB, Gelfend Y, Cohen S, Zick A, Sheva K, Nechushtan H, Peretz T, Meirovitz A.
    • Anticancer Res. 2022 Nov;42(11):5257-5263. doi: 10.21873/anticanres.16032.

    • Efficacy and safety of Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian carcinoma: A systematic review and meta-analysis of randomized controlled trials.
    • Zhang Y, Zhang L, Zhao Y, Wang S, Feng L.
    • Front Oncol. 2022 Oct 21;12:945867. doi: 10.3389/fonc.2022.945867.

    Related:

    •• Review registration number: CRD42022300367: Efficacy and safety of Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian cancer: A systematic review and meta-analysis of randomized controlled trials. (PROSPERO register. Accessed 2022 Nov 7.)

    • LitAlert ~~ GeneLit.com

    • Thermo Fisher Introduces Homologous Recombination Deficiency Score for Cancer Profiling Assay.
    • Han AP.
    • GenomeWeb. 2022 Nov 7.
    • News

    • Loss of Heterozygosity of BRCA1/2 as a Predictive Marker for Talazoparib Response.
    • Mizrahi AG, Hamad H, Gugenheim A, Nisman B, Kuznetz A, David IB, Gelfend Y, Cohen S, Zick A, Sheva K, Nechushtan H, Peretz T, Meirovitz A.
    • Anticancer Res. 2022 Nov;42(11):5257-5263. doi: 10.21873/anticanres.16032.

    • Efficacy and safety of Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian carcinoma: A systematic review and meta-analysis of randomized controlled trials.
    • Zhang Y, Zhang L, Zhao Y, Wang S, Feng L.
    • Front Oncol. 2022 Oct 21;12:945867. doi: 10.3389/fonc.2022.945867.

    Related:

    •• Review registration number: CRD42022300367: Efficacy and safety of Gemogenovatucel-T (Vigil) immunotherapy for advanced ovarian cancer: A systematic review and meta-analysis of randomized controlled trials. (PROSPERO register. Accessed 2022 Nov 7.)

    • LitAlert ~~ GeneLit.com

    • ASO Visual Abstract: Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome, and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer (HGSOC). A Multicenter, Retrospective Study of the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.
    • Glajzer J, Castillo-Tong DC, Richter R, Vergote I, Kulbe H, Vanderstichele A, Ruscito I, Trillsch F, Mustea A, Kreuzinger C, Gourley C, Gabra H, Taube ET, Dorigo O, Horst D, Keunecke C, Baum J, Angelotti T, Sehouli J, Braicu EI.
    • Ann Surg Oncol. 2022 Nov 5. doi: 10.1245/s10434-022-12681-z. Epub ahead of print.
    • Review

    Related:

    •• Original research:

    Impact of BRCA Mutation Status on Tumor Dissemination Pattern, Surgical Outcome and Patient Survival in Primary and Recurrent High-Grade Serous Ovarian Cancer: A Multicenter Retrospective Study by the Ovarian Cancer Therapy-Innovative Models Prolong Survival (OCTIPS) Consortium.

    • Genetic Testing Among Patients with High-Risk Breast, Ovarian, Pancreatic, and Prostate Cancers.
    • Clark NM, Roberts EA, Fedorenko C, Sun Q, Dubard-Gault M, Handford C, Yung R, Cheng HH, Sham JG, Norquist BM, Flanagan MR.
    • Ann Surg Oncol. 2022 Nov 5. doi: 10.1245/s10434-022-12755-y. Epub ahead of print.

    • Detection of microsatellite instability high (MSI-H) status by targeted plasma-based genotyping in metastatic breast cancer.
    • Vidula N, Lipman A, Kato S, Weipert C, Hesler K, Azzi G, Elkhanany A, Juric D, Rodriguez E, Faulkner C, Makhlouf P, Price K, O'Shaughnessy J, Bardia A.
    • NPJ Breast Cancer. 2022 Nov 4;8(1):117. doi: 10.1038/s41523-022-00490-2.

    • LitAlert ~~ GeneLit.com

    • Prognostic impact of germline BRCA1/2 pathogenic variants in breast cancer.
    • Corso G, Girardi A, Calvello M, Gandini S, Gaeta A, Marabelli M, Magnoni F, Veronesi P, Guerrieri-Gonzaga A, Bonanni B.
    • Breast Cancer Res Treat. 2022 Nov 4. doi: 10.1007/s10549-022-06776-0. Epub ahead of print.

    • A common IGF1R gene variant predicts later life breast cancer risk in women with preeclampsia.
    • Powell M, Fuller S, Gunderson E, Benz C.
    • Breast Cancer Res Treat. 2022 Nov 4. doi: 10.1007/s10549-022-06789-9. Epub ahead of print.

    • Characteristics of BRCA2 Mutated Prostate Cancer at Presentation.
    • Han H, Park CK, Cho NH, Lee J, Jang WS, Ham WS, Choi YD, Cho KS.
    • Int J Mol Sci. 2022 Nov 3;23(21):13426. doi: 10.3390/ijms232113426.

    • Development and Validation of a Breast Cancer Polygenic Risk Score on the Basis of Genetic Ancestry Composition.
    • Hughes E, Wagner S, Pruss D, Bernhisel R, Probst B, Abkevich V, Simmons T, Hullinger B, Judkins T, Rosenthal E, Roa B, Domchek SM, Eng C, Garber J, Gary M, Klemp J, Mukherjee S, Offit K, Olopade OI, Vijai J, Weitzel JN, Whitworth P, Yehia L, Gordon O, Pederson H, Kurian A, Slavin TP, Gutin A, Lanchbury JS.
    • JCO Precis Oncol. [2022 Nov 3];6:e2200084. doi: 10.1200/PO.22.00084.

    • Real-World Study of Regional Differences in Patient Demographics, Clinical Characteristics, and BRCA1/2 Mutation Testing in Patients with Human Epidermal Growth Factor Receptor 2-Negative Advanced Breast Cancer in the United States, Europe, and Israel.
    • Mahtani R, Niyazov A, Lewis K, Rider A, Massey L, Arondekar B, Lux MP.
    • Adv Ther. 2022 Oct 28. doi: 10.1007/s12325-022-02302-2. Epub ahead of print.

    • LitAlert ~~ GeneLit.com

    • Laboratory Cross-Comparison and Ring Test Trial for Tumor BRCA Testing in a Multicenter Epithelial Ovarian Cancer Series: The BORNEO GEICO 60-0 Study.
    • Garcia-Casado Z, Oaknin A, Mendiola M, Alkorta-Aranburu G, Antunez-Lopez JR, Moreno-Bueno G, Palacios J, Yubero A, Marquez R, Gallego A, Sanchez-Heras AB, Lopez-Guerrero JA, Perez-Segura C, Barretina-Ginesta P, Alarcon J, Gaba L, Marquez A, Matito J, Cueva J, Palacio I, Iglesias M, Arcusa A, Sanchez-Lorenzo L, Guerra-Alia E, Romero I, Vivancos A.
    • J Pers Med. 2022 Nov 4;12(11):1842. doi: 10.3390/jpm12111842.

    • BRCA Mutations, HRD Status Drive PARP Inhibitor Selection in Ovarian Cancer Maintenance.
    • Scott R, Rimel BJ.
    • OncLive. 2022 Nov 4.

    • Optimizing Therapy for Ovarian Cancer: Recent Data Highlights - Episode 9: The Rationale for PARP Inhibitor Treatment for HRD-Positive Ovarian Cancer.
    • Monk BJ, Coleman RL, Westin SN, Birrer MJ.
    • OncLive. Peer Exchange. 2022 Nov 4.

    • Optimizing Therapy for Ovarian Cancer: Recent Data Highlights - Episode 10: Antibody-Drug Conjugates in Ovarian Cancer Treatment.
    • Monk BJ, Coleman RL, Westin SN, Birrer MJ.
    • OncLive. Peer Exchange. 2022 Nov 4.

    • Familial history and prevalence of BRCA1, BRCA2 and TP53 pathogenic variants in HBOC Brazilian patients from a public healthcare service.
    • Matta BP, Gomes R, Mattos D, Olicio R, Nascimento CM, Ferreira GM, Brant AC, Boroni M, Furtado C, Lima V, Moreira MÂM, Dos Santos ACE.
    • Sci Rep. 2022 Nov 3;12(1):18629. doi: 10.1038/s41598-022-23012-3.

    • Exquisitely Platinum-Sensitive Triple-Negative Breast Cancer, Time for BRCA Methylation Testing?
    • Tan TJ, Fink JL, Tay TK, Jaradi B, Stone N, Waring P, Koo KM, Tan PH, Tan DS, Dent RA.
    • JCO Precis Oncol. 2022 Nov;6:e2200309. doi: 10.1200/PO.22.00309.
    • Case report

    • A moving target for drug discovery: Structure activity relationship and many genome (de)stabilizing functions of the RAD52 protein.
    • Bhat DS, Spies MA, Spies M.
    • DNA Repair (Amst). 2022 Oct 27;120:103421. doi: 10.1016/j.dnarep.2022.103421. Epub ahead of print.
    • Review

    • Recurrent Cervical Cancer Treated Successfully with Single-Agent PARP-Inhibitor, Olaparib.
    • Gross M, Spencer RJ.
    • Case Rep Obstet Gynecol. 2022 Oct 25;2022:6579715. doi: 10.1155/2022/6579715.

    • LitAlert ~~ GeneLit.com

    • Receipt of Bilateral Mastectomy Among Women With Hereditary Breast Cancer.
    • Reid S, Roberson ML, Koehler K, Shah T, Weidner A, Whisenant JG, Pal T.
    • JAMA Oncol. 2022 Nov 3. doi: 10.1001/jamaoncol.2022.5162. Epub ahead of print.

    • Clinical application of artificial neural network (ANN) modeling to predict BRCA1/2 germline deleterious variants in Chinese bilateral primary breast cancer patients.
    • Li Y, Chen L, Lv J, Chen X, Zeng B, Chen M, Guo W, Lin Y, Yu L, Hou J, Li J, Zhou P, Zhang W, Li S, Jin X, Cai W, Zhang K, Huang Y, Wang C, Fu F.
    • BMC Cancer. 2022 Nov 2;22(1):1125. doi: 10.1186/s12885-022-10160-y.

    • BRCA1/2 Mutation Testing in Patients with HER2-Negative Advanced Breast Cancer: Real-World Data from the United States, Europe, and Israel.
    • Mahtani R, Niyazov A, Arondekar B, Lewis K, Rider A, Massey L, Lux MP.
    • Cancers (Basel). 2022 Nov 2;14(21):5399. doi: 10.3390/cancers14215399.

    • Sequential Olaparib, Adavosertib Administration Overcomes Concurrent Use Toxicity Problems.
    • [No author given]
    • Inside Precision Medicine. Topics. Oncology. 2022 Nov 2.

    • Myriad Genetics to Submit Hereditary Cancer Risk Variants to ClinVar in 2023
    • Ray T.
    • GenomeWeb. 2022 Nov 1.
    • News

    • LitAlert ~~ GeneLit.com

    • Reducing the risk of breast cancer.
    • Pederson HJ, Al-Hilli Z, Kurian AW.
    • Cleve Clin J Med. 2022 Nov 1;89(11):643-652. doi: 10.3949/ccjm.89a.21113.

    • Olaparib Efficacy in Patients with Metastatic Castration-resistant Prostate Cancer and BRCA1, BRCA2 or ATM Alterations Identified by Testing Circulating Tumor DNA.
    • Matsubara N, de Bono J, Olmos D, Procopio G, Kawakami S, Ürün Y, van Alphen R, Flechon A, Carducci MA, Choi YD, Hotte SJ, Korbenfeld E, Kramer G, Agarwal N, Chi KN, Dearden S, Gresty C, Kang J, Poehlein C, Harrington EA, Hussain M.
    • Clin Cancer Res. 2022 Nov 1:CCR-21-3577. doi: 10.1158/1078-0432.CCR-21-3577. Epub ahead of print.

    • The avoiding late diagnosis of ovarian cancer (ALDO) project; a pilot national surveillance programme for women with pathogenic germline variants in BRCA1 and BRCA2.
    • Philpott S, Raikou M, Manchanda R, Lockley M, Singh N, Scott M, Evans DG, Adlard J, Ahmed M, Edmondson R, Woodward ER, Lamnisos A, Balega J, Brady AF, Sharma A, Izatt L, Kulkarni A, Tripathi V, Solomons JS, Hayes K, Hanson H, Snape K, Side L, Skates S, McGuire A, Rosenthal AN.
    • J Med Genet. 2022 Nov 1:jmedgenet-2022-108741. doi: 10.1136/jmg-2022-108741. Epub ahead of print.