{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T21:12:54Z","timestamp":1791666774006,"version":"4.3.4"},"reference-count":45,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T00:00:00Z","timestamp":1662681600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked, inherited genetic disease caused by a functional deficiency of lysosomal \u03b1-galactosidase, leading to the accumulation of glycosphingolipids in virtually all of the body\u2019s cell types and fluids. Patients with rare genetic diseases and non-specific symptoms often experience substantial diagnostic delays, which can negatively impact the prompt initiation of treatment. If FD is not treated specifically, end organ damage (such as chronic renal failure, hypertrophic cardiomyopathy with arrhythmia, and strokes) impairs quality of life and reduces life expectancy. Patients and Methods: For 83 consecutive patients with FD referred to the Russian reference center for lysosomal storage diseases, family trees were built and genetic testing (cascade genotyping) was offered to family members. Results: The pathogenic GLA variant associated with FD was identified for all 83 probands. Family testing using cascade genotyping enabled the identification of 165 additional cases of FD among the tested 331 at-risk family members. Discussion: This is the first study to have described family screening in a large Russian cohort of patients with FD and chronic kidney disease. Raising awareness of FD among clinicians is important for earlier diagnosis and specific treatment.<\/jats:p>","DOI":"10.3390\/genes13091619","type":"journal-article","created":{"date-parts":[[2022,9,9]],"date-time":"2022-09-09T04:54:41Z","timestamp":1662699281000},"page":"1619","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["The Benefits of Family Screening in Rare Diseases: Genetic Testing Reveals 165 New Cases of Fabry Disease among At-Risk Family Members of 83 Index Patients"],"prefix":"10.3390","volume":"13","author":[{"given":"Sergey","family":"Moiseev","sequence":"first","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0621-7054","authenticated-orcid":false,"given":"Ekaterina","family":"Tao","sequence":"additional","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexey","family":"Moiseev","sequence":"additional","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"},{"name":"Faculty of Medicine, Lomonosov Moscow State University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nikolay","family":"Bulanov","sequence":"additional","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ekaterina","family":"Filatova","sequence":"additional","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Victor","family":"Fomin","sequence":"additional","affiliation":[{"name":"Tareev Clinic of Internal Disease, Sechenov First Moscow State Medical University, 119991 Moscow, Russia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8355-007X","authenticated-orcid":false,"given":"Dominique P.","family":"Germain","sequence":"additional","affiliation":[{"name":"Geneo Referral Centre for Fabry Disease, Fili\u00e8re G2M, MetabERN European Reference Network, Paris-Saclay University, 92380 Garches, France"},{"name":"Second Department of Internal Medicine, First Faculty of Medicine, Charles University, 12808 Prague, Czech Republic"},{"name":"Faculty of Medicine, University of Puthisastra, Phnom Penh 12211, Cambodia"},{"name":"Division of Medical Genetics, University of Versailles, 78180 Montigny, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,9,9]]},"reference":[{"key":"ref_1","first-page":"1186","article-title":"Nature and frequency of mutations in the alpha-galactosidase A gene that cause Fabry disease","volume":"53","author":"Eng","year":"1993","journal-title":"Am. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1007\/s004390050292","article-title":"Fluorescence-assisted mismatch analysis (FAMA) for exhaustive screening of the alpha-galactosidase A gene and detection of carriers in Fabry disease","volume":"98","author":"Germain","year":"1996","journal-title":"Hum. Genet."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"338","DOI":"10.7326\/0003-4819-138-4-200302180-00014","article-title":"Fabry disease, an under-recognized multisystemic disorder: Expert recommendations for diagnosis, management, and enzyme replacement therapy","volume":"138","author":"Desnick","year":"2003","journal-title":"Ann. Intern. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1186\/1750-1172-5-30","article-title":"Fabry disease","volume":"5","author":"Germain","year":"2010","journal-title":"Orphanet J. Rare Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1016\/j.ymgme.2018.02.014","article-title":"Fabry disease revisited: Management and treatment recommendations for adult patients","volume":"123","author":"Ortiz","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"2812","DOI":"10.1073\/pnas.0712309105","article-title":"Elevated globotriaosylsphingosine is a hallmark of Fabry disease","volume":"105","author":"Aerts","year":"2008","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1111\/cns.12542","article-title":"Pain in Fabry disease: Practical recommendations for diagnosis and treatment","volume":"22","author":"Politei","year":"2016","journal-title":"CNS Neurosci. Ther."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"2220","DOI":"10.2215\/CJN.04340510","article-title":"Prognostic indicators of renal disease progression in adults with Fabry disease: Natural history data from the Fabry Registry","volume":"5","author":"Wanner","year":"2010","journal-title":"Clin. J. Am. Soc. Nephrol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1076","DOI":"10.1002\/ejhf.1960","article-title":"An expert consensus document on the management of cardiovascular manifestations of Fabry disease","volume":"22","author":"Linhart","year":"2020","journal-title":"Eur. J. Heart Fail."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"302","DOI":"10.1161\/STROKEAHA.114.006283","article-title":"Cerebrovascular involvement in Fabry disease: Current status of knowledge","volume":"46","author":"Kolodny","year":"2015","journal-title":"Stroke"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"57","DOI":"10.1111\/j.1651-2227.2002.tb03112.x","article-title":"Endothelial markers and homocysteine in patients with classic Fabry disease","volume":"91","author":"Demuth","year":"2002","journal-title":"Acta Paediatr."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"44","DOI":"10.1111\/cge.12613","article-title":"X-chromosome inactivation in female patients with Fabry disease","volume":"89","author":"Echevarria","year":"2016","journal-title":"Clin. Genet."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/j.ymgme.2018.09.007","article-title":"The effect of enzyme replacement therapy on clinical outcomes in female patients with Fabry disease-A systematic literature review by a European panel of experts","volume":"126","author":"Germain","year":"2019","journal-title":"Mol. Genet. Metab."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1111\/cge.13546","article-title":"Consensus recommendations for diagnosis, management and treatment of Fabry disease in paediatric patients","volume":"96","author":"Germain","year":"2019","journal-title":"Clin. Genet."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"641","DOI":"10.1093\/qjmed\/hcq117","article-title":"Fabry disease: A review of current management strategies","volume":"103","author":"Mehta","year":"2010","journal-title":"QJM"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1056\/NEJMoa1510198","article-title":"Treatment of Fabry\u2019s Disease with the Pharmacologic Chaperone Migalastat","volume":"375","author":"Germain","year":"2016","journal-title":"N. Engl. J. Med."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"189","DOI":"10.1016\/j.ymgme.2018.06.004","article-title":"European expert consensus statement on therapeutic goals in Fabry disease","volume":"124","author":"Wanner","year":"2018","journal-title":"Mol. Genet. Metab."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1159\/000494678","article-title":"Results of Fabry disease screening in male pre-end stage renal disease patients with unknown etiology found through the Platform of a Chronic Kidney Disease Education Program in a Northern Taiwan Medical Center","volume":"43","author":"Lin","year":"2018","journal-title":"Kidney Blood Press. Res."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1111\/j.1399-0004.2009.01166.x","article-title":"A successful screening for Fabry disease in a Chinese dialysis patient population","volume":"76","author":"Lv","year":"2009","journal-title":"Clin. Genet."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1093\/ndt\/gfl528","article-title":"A nationwide blood spot screening study for Fabry disease in the Czech Republic haemodialysis patient population","volume":"22","author":"Merta","year":"2007","journal-title":"Nephrol. Dial. Transpl."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1046\/j.1523-1755.2003.00160.x","article-title":"Fabry disease: Detection of undiagnosed hemodialysis patients and identification of a \u201crenal variant\u201d phenotype","volume":"64","author":"Nakao","year":"2003","journal-title":"Kidney Int."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"42","DOI":"10.1016\/j.gene.2013.05.050","article-title":"Screening for Fabry disease in patients undergoing dialysis for chronic renal failure in Turkey: Identification of new case with novel mutation","volume":"527","author":"Okur","year":"2013","journal-title":"Gene"},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"221","DOI":"10.1159\/000448740","article-title":"Targeted screening of Fabry disease in male hemodialysis patients in Brazil highlights importance of family screening","volume":"134","author":"Silva","year":"2016","journal-title":"Nephron"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1159\/000495886","article-title":"The prevalence and clinical features of Fabry disease in hemodialysis patients: Russian Nationwide Fabry Dialysis Screening Program","volume":"141","author":"Moiseev","year":"2019","journal-title":"Nephron"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1016","DOI":"10.1159\/000452605","article-title":"The prevalence of Fabry disease in patients with chronic kidney disease in Turkey: The TURKFAB Study","volume":"41","author":"Turkmen","year":"2016","journal-title":"Kidney Blood Press. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1159\/000479895","article-title":"A novel missense GLA mutation (p.G35V) detected in hemodialysis screening leads to severe systemic manifestations of Fabry disease in men and women","volume":"138","author":"Veloso","year":"2018","journal-title":"Nephron"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e001639","DOI":"10.1161\/CIRCGENETICS.116.001639","article-title":"Fabry disease in families with hypertrophic cardiomyopathy: Clinical manifestations in the classic and later-onset phenotypes.; et al","volume":"10","author":"Adalsteinsdottir","year":"2017","journal-title":"Circ. Cardiovasc. Genet."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1136\/hrt.2010.200188","article-title":"FOCUS study investigators. Screening patients with hypertrophic cardiomyopathy for Fabry disease using a filter-paper test: The FOCUS study","volume":"97","author":"Caudron","year":"2011","journal-title":"Heart"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e1","DOI":"10.1016\/j.amjmed.2017.09.010","article-title":"Identification of Fabry disease in a tertiary referral cohort of patients with hypertrophic cardiomyopathy","volume":"131","author":"Maron","year":"2018","journal-title":"Am. J. Med."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1644","DOI":"10.1016\/j.mayocp.2019.05.003","article-title":"Strategies of screening for Fabry disease in patients with unexplained left ventricular hypertrophy","volume":"94","author":"Moiseev","year":"2019","journal-title":"Mayo Clin. Proc."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1088","DOI":"10.1016\/j.clineuro.2012.11.003","article-title":"Phenotypical characterization of \u03b1-galactosidase A gene mutations identified in a large Fabry disease screening program in stroke in the young","volume":"115","author":"Yperzeele","year":"2013","journal-title":"Clin. Neurol. Neurosurg."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"261","DOI":"10.1136\/jmedgenet-2017-105080","article-title":"Fabry Disease: Prevalence of affected males and heterozygotes with pathogenic GLA mutations identified by screening renal, cardiac and stroke clinics, 1995\u20132017","volume":"55","author":"Doheny","year":"2018","journal-title":"J. Med. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1666","DOI":"10.1002\/mgg3.1666","article-title":"The benefits and challenges of family screening in rare genetic diseases\u2013lessons from Fabry disease","volume":"9","author":"Germain","year":"2021","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"492","DOI":"10.1002\/mgg3.389","article-title":"Phenotypic characteristics of the p.Asn215Ser (p.N215S) GLA mutation in male and female patients with Fabry disease: A multicenter Fabry Registry study","volume":"6","author":"Germain","year":"2018","journal-title":"Mol. Genet. Genom. Med."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1007\/s10897-007-9128-x","article-title":"Diagnosis of Fabry disease via analysis of family history","volume":"17","author":"Laney","year":"2008","journal-title":"J. Genet. Couns."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Gragnaniello, V., Burlina, A.P., Polo, G., Giuliani, A., Salviati, L., Duro, G., Cazzorla, C., Rubert, L., Maines, E., and Germain, D.P. (2021). Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience. Biomolecules, 11.","DOI":"10.3390\/biom11070951"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"180","DOI":"10.1016\/j.nephro.2021.03.002","article-title":"Screeninf for Fabry disease in male patients with end-stage renal disease in Western France","volume":"17","author":"Vigneau","year":"2021","journal-title":"Nephrol. Ther."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"45","DOI":"10.1002\/jmd2.12035","article-title":"Prevalence of Fabry disease in male dialysis patients: Argentinean screening study","volume":"48","author":"Frabasil","year":"2019","journal-title":"JIMD Rep."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1407","DOI":"10.1161\/01.CIR.0000012626.81324.38","article-title":"Prevalence of Anderson-Fabry disease in male patients with late onset hypertrophic cardiomyopathy","volume":"105","author":"Sachdev","year":"2002","journal-title":"Circulation"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1086\/504601","article-title":"High incidence of later-onset Fabry disease revealed by newborn screening","volume":"79","author":"Spada","year":"2006","journal-title":"Am. J. Hum. Genet."},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Germain, D.P., Avan, P., Chassaing, A., and Bonfils, P. (2002). Patients affected with Fabry disease have an increased incidence of progressive hearing loss and sudden deafness: An investigation of twenty-two hemizygous male patients. BMC Med. Genet., 3.","DOI":"10.1186\/1471-2350-3-10"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"790","DOI":"10.1007\/s10545-007-0616-9","article-title":"Natural history of the respiratory involvement in Anderson-Fabry disease","volume":"30","author":"Magage","year":"2007","journal-title":"J. Inherit. Metab. Dis."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"e12914","DOI":"10.1111\/ijcp.12914","article-title":"Time delays in the diagnosis and treatment of Fabry disease","volume":"71","author":"Reisin","year":"2017","journal-title":"Int. J. Clin. Pract."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"708","DOI":"10.1006\/bbrc.1999.0310","article-title":"Fabry disease: Identification of novel \u03b1-galactosidase A mutations and molecular carrier detection by use of fluorescent chemical cleavage of mismatches","volume":"257","author":"Germain","year":"1999","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"e00794","DOI":"10.1002\/mgg3.794","article-title":"Fabry pedigree analysis: A successful program for targeted genetic approach","volume":"7","author":"Rozenfeld","year":"2019","journal-title":"Mol. Genet. Genom. Med."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/9\/1619\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T00:28:08Z","timestamp":1760142488000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/13\/9\/1619"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,9,9]]},"references-count":45,"journal-issue":{"issue":"9","published-online":{"date-parts":[[2022,9]]}},"alternative-id":["genes13091619"],"URL":"https:\/\/doi.org\/10.3390\/genes13091619","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,9,9]]}}}