BACKGROUND: Family genetic testing of patients newly diagnosed with a rare genetic disease can improve early diagnosis of family members, allowing patients to receive disease-specific therapies when available. Fabry disease, an X-linked lysosomal storage disorder caused by pathogenic variants in GLA, can lead to end-stage renal disease, cardiac arrhythmias, and stroke. Diagnostic delays are common due to the rarity of the disease and non-specificity of early symptoms. Newborn screening and screening of at-risk populations, (e.g., patients with hypertrophic cardiomyopathy or undiagnosed nephropathies) can identify individuals with Fabry disease. Subsequent cascade genotyping of family members may disclose a greater number of affected individuals, often at younger age than they would have been diagnosed otherwise. METHODS: We conducted a literature search to identify all published data on family genetic testing for Fabry disease, and discussed these data, experts' own experiences with family genetic testing, and the barriers to this type of screening that are present in their respective countries. RESULTS: There are potential barriers that make implementation of family genetic testing challenging in some countries. These include associated costs and low awareness of its importance, and cultural and societal issues. Regionally, there are barriers associated with population educational levels, national geography and infrastructures, and a lack of medical geneticists. CONCLUSION: In this review, the worldwide experience of an international group of experts of Fabry disease highlights the issues faced in the family genetic testing of patients affected with rare genetic diseases.

• Klíčová slova
• Fabry disease, at-risk populations screening, cascade genotyping, early diagnosis, family genetic testing, pedigree drawing, rare disease,
• MeSH
• Fabryho nemoc diagnóza   genetika   MeSH
• genetické testování metody   normy   MeSH
• lidé MeSH
• rodokmen MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

BACKGROUND: Fabry disease (FD, OMIM #301500) is a rare, progressive, X-linked, inherited genetic disease caused by a functional deficiency of lysosomal α-galactosidase, leading to the accumulation of glycosphingolipids in virtually all of the body's 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.

• Klíčová slova
• Fabry disease, cascade genotyping, early diagnosis, family screening, rare diseases,
• MeSH
• alfa-galaktosidasa genetika   MeSH
• chronická renální insuficience * diagnóza   genetika   MeSH
• Fabryho nemoc * diagnóza   genetika   metabolismus   MeSH
• genetické testování MeSH
• glykosfingolipidy MeSH
• kvalita života MeSH
• lidé MeSH
• mutace MeSH
• rodina MeSH
• vzácné nemoci genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• alfa-galaktosidasa MeSH
• glykosfingolipidy MeSH

Although awareness of familial hypercholesterolemia (FH) is increasing, this common, potentially fatal, treatable condition remains underdiagnosed. Despite FH being a genetic disorder, genetic testing is rarely used. The Familial Hypercholesterolemia Foundation convened an international expert panel to assess the utility of FH genetic testing. The rationale includes the following: 1) facilitation of definitive diagnosis; 2) pathogenic variants indicate higher cardiovascular risk, which indicates the potential need for more aggressive lipid lowering; 3) increase in initiation of and adherence to therapy; and 4) cascade testing of at-risk relatives. The Expert Consensus Panel recommends that FH genetic testing become the standard of care for patients with definite or probable FH, as well as for their at-risk relatives. Testing should include the genes encoding the low-density lipoprotein receptor (LDLR), apolipoprotein B (APOB), and proprotein convertase subtilisin/kexin 9 (PCSK9); other genes may also need to be considered for analysis based on patient phenotype. Expected outcomes include greater diagnoses, more effective cascade testing, initiation of therapies at earlier ages, and more accurate risk stratification.

• Klíčová slova
• cascade testing, consensus statement, familial hypercholesterolemia, genetic counseling, genetic testing,
• MeSH
• apolipoproteiny B krev   genetika   MeSH
• genetické poradenství metody   normy   MeSH
• genetické testování metody   normy   MeSH
• hyperlipoproteinemie typ II krev   diagnóza   genetika   MeSH
• lidé MeSH
• proproteinkonvertasa subtilisin/kexin typu 9 krev   genetika   MeSH
• receptory LDL krev   genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• apolipoproteiny B MeSH
• LDLR protein, human MeSH Prohlížeč
• PCSK9 protein, human MeSH Prohlížeč
• proproteinkonvertasa subtilisin/kexin typu 9 MeSH
• receptory LDL MeSH

Genetic testing for pathogenic COL4A3-5 variants is usually undertaken to investigate the cause of persistent hematuria, especially with a family history of hematuria or kidney function impairment. Alport syndrome experts now advocate genetic testing for persistent hematuria, even when a heterozygous pathogenic COL4A3 or COL4A4 is suspected, and cascade testing of their first-degree family members because of their risk of impaired kidney function. The experts recommend too that COL4A3 or COL4A4 heterozygotes do not act as kidney donors. Testing for variants in the COL4A3-COL4A5 genes should also be performed for persistent proteinuria and steroid-resistant nephrotic syndrome due to suspected inherited FSGS and for familial IgA glomerulonephritis and kidney failure of unknown cause.

• Klíčová slova
• Alport syndrome, COL4A3, COL4A4, COL4A5, FSGS, collagen IV, digenic Alport syndrome, genetic testing, kidney cysts, thin basement membrane nephropathy,
• MeSH
• autoantigeny genetika   MeSH
• dědičná nefritida diagnóza   genetika   terapie   MeSH
• genetické testování normy   MeSH
• kolagen typu IV genetika   MeSH
• lidé MeSH
• směrnice pro lékařskou praxi jako téma MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• autoantigeny MeSH
• COL4A5 protein, human MeSH Prohlížeč
• kolagen typu IV MeSH
• type IV collagen alpha3 chain MeSH Prohlížeč

PURPOSE: Genetic testing in consanguineous families advances the general comprehension of pathophysiological pathways. However, short stature (SS) genetics remain unexplored in a defined consanguineous cohort. This study examines a unique pediatric cohort from Sulaimani, Iraq, aiming to inspire a genetic testing algorithm for similar populations. METHODS: Among 280 SS referrals from 2018-2020, 64 children met inclusion criteria (from consanguineous families; height ≤ -2.25 SD), 51 provided informed consent (30 females; 31 syndromic SS) and underwent investigation, primarily via exome sequencing. Prioritized variants were evaluated by the American College of Medical Genetics and Genomics standards. A comparative analysis was conducted by juxtaposing our findings against published gene panels for SS. RESULTS: A genetic cause of SS was elucidated in 31 of 51 (61%) participants. Pathogenic variants were found in genes involved in the GH-IGF-1 axis (GHR and SOX3), thyroid axis (TSHR), growth plate (CTSK, COL1A2, COL10A1, DYM, FN1, LTBP3, MMP13, NPR2, and SHOX), signal transduction (PTPN11), DNA/RNA replication (DNAJC21, GZF1, and LIG4), cytoskeletal structure (CCDC8, FLNA, and PCNT), transmembrane transport (SLC34A3 and SLC7A7), enzyme coding (CYP27B1, GALNS, and GNPTG), and ciliogenesis (CFAP410). Two additional participants had Silver-Russell syndrome and 1 had del22q.11.21. Syndromic SS was predictive in identifying a monogenic condition. Using a gene panel would yield positive results in only 10% to 33% of cases. CONCLUSION: A tailored testing strategy is essential to increase diagnostic yield in children with SS from consanguineous populations.

• Klíčová slova
• Consanguinity, Genetic testing algorithm, Pediatric endocrinology, Short stature, Short stature genes,
• MeSH
• algoritmy MeSH
• dítě MeSH
• genetické testování * metody   MeSH
• lidé MeSH
• mladiství MeSH
• mutace genetika   MeSH
• nanismus genetika   diagnóza   MeSH
• pokrevní příbuzenství * MeSH
• poruchy růstu genetika   diagnóza   MeSH
• předškolní dítě MeSH
• rodokmen MeSH
• sekvenování exomu metody   MeSH
• tělesná výška genetika   MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Irák MeSH

Pheochromocytomas (PHEOs) and paragangliomas (PGLs) are rare, catecholamine-producing tumors that are usually sporadic. However, about 30% of these tumors have been identified as being of inherited origin. To date, nine genes have been confirmed as participating in PHEO or PGL tumorigenesis. Germline mutations were found in 100% of syndromic cases and in about 90% of patients with positive familial history. In nonsyndromic patients with apparently sporadic tumors, genetic mutations have been found in up to 27%, and genetic testing is now recommended for all patients with PHEOs and PGLs. Patients with syndromic lesions, a positive family history, or both should be tested for the appertaining gene. Recent discoveries have shown that the order of tested genes in nonsyndromic, nonfamilial cases can be based on histologic evaluation, location, and the biochemical phenotype of PHEOs and PGLs--the "rule of three." Identification of a gene mutation may lead to early diagnosis and treatment, regular surveillance, and a better prognosis for patients and their relatives.

• MeSH
• asymptomatické nemoci mortalita   MeSH
• časná detekce nádoru MeSH
• dospělí MeSH
• feochromocytom * diagnóza   genetika   mortalita   terapie   MeSH
• genetické testování * MeSH
• katecholaminy genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• míra přežití MeSH
• mnohočetná endokrinní neoplazie typ 2A * diagnóza   genetika   mortalita   terapie   MeSH
• nádory nadledvin * diagnóza   genetika   mortalita   terapie   MeSH
• sukcinátdehydrogenasa genetika   MeSH
• výsledek terapie MeSH
• zárodečné mutace MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• katecholaminy MeSH
• sukcinátdehydrogenasa MeSH

Hereditary cancer syndromes are frequently seen in young cancer patients and patients with a positive family history. Genetic testing is important for the identification of high-risk individuals, and for the early introduction of specialized preventive care or prophylactic surgeries. High-risk tumour suppressor genes (BRCA1 and BRCA2) and DNA repair genes (MLH1, MSH2 and MSH6) are responsible for a substantial part of hereditary breast, ovarian and colorectal cancer. Other hereditary cancers are seen less frequently, but genetic testing has increased for many other site-specific cancers and complex syndromes. Genetic centres and molecular genetic laboratories are located mostly within university or regional hospitals. Some genetic centres are private. It is highly recommended (Czech Society for Medical Genetics) that all laboratories are accredited according to ISO 15,189 and that genetic testing of hereditary cancer syndromes is indicated by medical geneticists. The indication criteria and prevention strategies were published in Supplement 22 of Clinical Oncology 2009 (in Czech). Preventive care for high-risk individuals is organized by thirteen Oncology Centres, which provide most of the oncology care in the Czech Republic. Genetic testing and preventive care for high-risk individuals and mutation carriers is covered by health insurance. The molecular genetic laboratory at the MMCI provides molecular genetic testing of BRCA1, BRCA2, CHEK2 for hereditary breast/ovarian cancer, MLH1, MSH2, MSH6 for Lynch syndrome,TP53 for Li-Fraumeni syndrome, CDKN2A for familial malignant melanoma syndrome and CDH1 gene for hereditary diffuse gastric cancer. Other syndromes are tested in specialized laboratories elsewhere.The use of genetic testing is increasing because of more frequent referrals from oncologists and other specialists and the increasing variety of genes tested. However, in some patients the testing is not recommended and other family members are dying because of the late diagnosis of hereditary syndrome. Greater awareness of the importance of genetic testing in oncology is needed.

• MeSH
• dědičné nádorové syndromy diagnóza   genetika   prevence a kontrola   MeSH
• genetická predispozice k nemoci MeSH
• genetické testování * MeSH
• lidé MeSH
• mutace MeSH
• rodokmen MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH

PURPOSE: Preimplantation genetic testing for monogenic disorders (PGT-M) allows early diagnosis in embryos conceived in vitro. PGT-M helps to prevent known genetic disorders in affected families and ensures that pathogenic variants in the male or female partner are not passed on to offspring. The trend in genetic testing of embryos is to provide a comprehensive platform that enables robust and reliable testing for the causal pathogenic variant(s), as well as chromosomal abnormalities that commonly occur in embryos. In this study, we describe PGT protocol that allows direct mutation testing, haplotyping, and aneuploidy screening. METHODS: Described PGT protocol called OneGene PGT allows direct mutation testing, haplotyping, and aneuploidy screening using next-generation sequencing (NGS). Whole genome amplification product is combined with multiplex PCR used for SNP enrichment. Dedicated bioinformatic tool enables mapping, genotype calling, and haplotyping of informative SNP markers. A commercial software was used for aneuploidy calling. RESULTS: OneGenePGT has been implemented for seven of the most common monogenic disorders, representing approximately 30% of all PGT-M indications at our IVF centre. The technique has been thoroughly validated, focusing on direct pathogenic variant testing, haplotype identification, and chromosome abnormality detection. Validation results show full concordance with Sanger sequencing and karyomapping, which were used as reference methods. CONCLUSION: OneGene PGT is a comprehensive, robust, and cost-effective method that can be established for any gene of interest. The technique is particularly suitable for common monogenic diseases, which can be performed based on a universal laboratory protocol without the need for set-up or pre-testing.

• Klíčová slova
• Aneuploidy, Monogenic disorders, Next-generation sequencing, Preimplantation genetic testing,
• MeSH
• aneuploidie MeSH
• blastocysta patologie   MeSH
• genetické testování metody   MeSH
• lidé MeSH
• mutace genetika   MeSH
• preimplantační diagnóza * metody   MeSH
• těhotenství MeSH
• vysoce účinné nukleotidové sekvenování metody   MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• těhotenství MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

Genetic test results can have considerable importance for patients, their parents and more remote family members. Clinical therapy and surveillance, reproductive decisions and genetic diagnostics in family members, including prenatal diagnosis, are based on these results. The genetic test report should therefore provide a clear, concise, accurate, fully interpretative and authoritative answer to the clinical question. The need for harmonizing reporting practice of genetic tests has been recognised by the External Quality Assessment (EQA), providers and laboratories. The ESHG Genetic Services Quality Committee has produced reporting guidelines for the genetic disciplines (biochemical, cytogenetic and molecular genetic). These guidelines give assistance on report content, including the interpretation of results. Selected examples of genetic test reports for all three disciplines are provided in an annexe.

• MeSH
• cytogenetické vyšetření MeSH
• diagnostické techniky molekulární MeSH
• genetické poradenství MeSH
• genetické testování normy   MeSH
• lidé MeSH
• prenatální diagnóza MeSH
• zajištění kvality zdravotní péče MeSH
• zveřejnění normy   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• směrnice pro lékařskou praxi MeSH

BACKGROUND: Previous studies have investigated various factors that can determine the attitudes of the citizens considering genetic testing. However, none of them investigated how these attitudes may differ between the Visegrad countries. METHODS: In this cross-sectional study a questionnaire developed by Dutch researchers was translated and used in Hungary, Slovakia, Czechia and Poland. In each country 1000 adult citizens were asked on the topics of personal benefits regarding genetic tests, genetic determinism, and finally, the availability and usage of genetic testing. Multivariate robust regression model was created including several possible influencing factors (such as age, sex, education, marital status, religiousness, and having a genetic test within the nuclear family) to identify the possible differences between the four countries. RESULTS: The Hungarian citizens had the most positive opinion on the personal benefits of genetic testing followed by the Czech, Slovak and Polish. All differences were significant in this regard. Considering genetic determinism, the Slovak citizens had a significantly firmer belief in this issue compared to the Hungarians. No other significant differences were observed in this domain. On the topic of the availability and use of genetic testing the Hungarian citizens had the most accepting opinion among the four countries, followed by the Czech citizens. In this domain the Polish and Slovak answers did not differ significantly from each other. CONCLUSIONS: Significant differences were observed even when considering various confounding effects. As the underlying reasons for these discrepancies are unknown, future studies should investigate this enigma among the four countries.

• Klíčová slova
• Attitudes, Citizens, Genetic testing, Public, Visegrad countries,
• MeSH
• dospělí MeSH
• genetické testování * MeSH
• lidé MeSH
• postoj * MeSH
• průřezové studie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• Geografické názvy
• Česká republika MeSH
• Maďarsko MeSH
• Polsko MeSH
• Slovenská republika MeSH