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15 záznamů v Medvik Filtry

Článek

A founder COL4A4 pathogenic variant resulting in autosomal recessive Alport syndrome accounts for most genetic kidney failure in Romani people

Plevova, Pavlina
Autor Plevova, Pavlina Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia Department of Biomedical Sciences, Faculty of Medicine, University of Ostrava, Ostrava, Czechia
Indrakova, Jana
Autor Indrakova, Jana Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Savige, Judy
Autor Savige, Judy Department of Medicine (Melbourne Health and Northern Health), The University of Melbourne, Royal Melbourne Hospital, Melbourne, Australia
Kuhnova, Petra
Autor Kuhnova, Petra Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Tvrda, Petra
Autor Tvrda, Petra Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Cerna, Dita
Autor Cerna, Dita Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Hilscherova, Sarka
Autor Hilscherova, Sarka Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Kudrejova, Monika
Autor Kudrejova, Monika Department of Clinical and Molecular Pathology and Medical Genetics, University Hospital Ostrava, Ostrava, Czechia
Polendova, Daniela
Autor Polendova, Daniela Department of Medical Genetics, Faculty of Medicine in Plzeň, Charles University and University Hospital Plzeň, Plzeň, Czechia
Jaklova, Radka
Autor Jaklova, Radka Department of Medical Genetics, Faculty of Medicine in Plzeň, Charles University and University Hospital Plzeň, Plzeň, Czechia

Frontiers in medicine. 2023 ; 10 (-) : 1096869. [pub] 20230208

Front. med.
ISSN 2296-858X
Medvik
Zdroj

INTRODUCTION: Romani people have a high prevalence of kidney failure. This study examined a Romani cohort for pathogenic variants in the COL4A3, COL4A4, and COL4A5 genes that are affected in Alport syndrome (AS), a common cause of genetic kidney disease, characterized by hematuria, proteinuria, end-stage kidney failure, hearing loss, and eye anomalies. MATERIALS AND METHODS: The study included 57 Romani from different families with clinical features that suggested AS who underwent next-generation sequencing (NGS) of the COL4A3, COL4A4, and COL4A5 genes, and 83 family members. RESULTS: In total, 27 Romani (19%) had autosomal recessive AS caused by a homozygous pathogenic c.1598G>A, p.Gly533Asp variant in COL4A4 (n = 20) or a homozygous c.415G>C, p.Gly139Arg variant in COL4A3 (n = 7). For p.Gly533Asp, 12 (80%) had macroscopic hematuria, 12 (63%) developed end-stage kidney failure at a median age of 22 years, and 13 (67%) had hearing loss. For p.Gly139Arg, none had macroscopic hematuria (p = 0.023), three (50%) had end-stage kidney failure by a median age of 42 years (p = 0.653), and five (83%) had hearing loss (p = 0.367). The p.Gly533Asp variant was associated with a more severe phenotype than p.Gly139Arg, with an earlier age at end-stage kidney failure and more macroscopic hematuria. Microscopic hematuria was very common in heterozygotes with both p.Gly533Asp (91%) and p.Gly139Arg (92%). CONCLUSION: These two founder variants contribute to the high prevalence of kidney failure in Czech Romani. The estimated population frequency of autosomal recessive AS from these variants and consanguinity by descent is at least 1:11,000 in Czech Romani. This corresponds to a population frequency of autosomal dominant AS from these two variants alone of 1%. Romani with persistent hematuria should be offered genetic testing.

Publikační typ
časopisecké články MeSH

Článek

Hereditární renální nádorové syndromy
[Hereditary renal cell carcinoma syndromes]

Česká urologie. 2020 ; 24 (1) : 26-41.

ISSN 1211-8729
Medvik
Zdroj

V posledních letech dochází ke zvyšování počtu definovaných hereditárních nádorových syndromů, z nichž některé jsou spojeny s predispozicí k rozvoji renálního karcinomu. Na hereditární renální nádorový syndrom je třeba pomýšlet u mladých jedinců s renálním karcinomem, u pacientů s pozitivní rodinnou anamnézou nádorů ledvin, dále u renálních lézí bilaterálních a multifokálních a při výskytu extrarenálních symptomů charakteristických pro některý ze syndromů. Mezi nejčastější hereditární nádorové syndromy asociované s renálním karcinomem patří syndrom von Hippel Lindau, Birt Hogg Dubé syndrom, hereditární papilární renální karcinom, hereditární leiomyomatóza a renální karcinom, sukcinátdehydrogenáza deficientní renální karcinom, komplex tuberózní sklerózy a Cowdenův syndrom. V souvislosti s hereditárním renálním karcinomem jsou popsány mutace v tumor supresorových genech (VHL, BAP1, PTEN, TSC1, TSC2) i v protoonkogenech (MET) V rámci jednotlivých syndromů se setkáváme s rozdíly ve stupni penetrance onemocnění, v histologii jednotlivých typů renálního karcinomu, v jeho agresivitě a metastatickém potenciálu, a tedy i v následné léčbě a dispenzarizaci.

In recent years, there has been an increase in the number of defined hereditary syndromes, some of which may predispose to kidney cancer. Hereditary renal cell carcinoma syndromes are often suggested by early age of onset, family history of kidney cancer, multifocal or bilateral lesions and the presence of other extrarenal lesions typical for the respective syndrome. The most common encountered syndromes are von Hippel Lindau, Birt-Hogg-Dubé, hereditary papillary renal cell carcinoma, hereditary leiomyomatosis and renal cell carcinoma, succinate dehydrogenase deficient renal cell carcinoma, tuberous sclerosis complex and Cowden syndrome. Related to hereditary renal cancer syndromes, germline mutations in tumor suppressor genes (VHL, BAP1, PTEN, TSC1, TSC2) and protooncogenes (MET) are described. Different histological subtypes are found among hereditary kidney cancer syndromes. The degree of kidney cancer penetrance, tumor aggressiveness, metastatic potential widely vary and the treatment and surveillance of kidney cancer is different among hereditary syndromes.

Klíčová slova
hereditární syndrom, zárodečná mutace,
MeSH
karcinom z renálních buněk * genetika MeSH
lidé MeSH
surveillance populace MeSH
Check Tag
lidé MeSH
Publikační typ
práce podpořená grantem MeSH
přehledy MeSH

Článek

Late diagnosis of complete androgen insensitivity syndrome and transmission/carriers of the condition in a family with mutation c.2495G> T p.(Arg832Leu) in exon 7 of the androgen receptor gene: genetic, clinical and ethical aspects

Biomedical papers of the Medical Faculty of the University Palacký, Olomouc Czech Republic. 2019 ; 163 (4) : 379-382. [pub] 20181106

Biomed. Pap. Fac. Med. Palacký Univ. Olomouc Czech Repub. (Print)
ISSN 1213-8118
Medvik
Zdroj

BACKGROUND: The complete androgen insensitivity syndrome (CAIS) is a rare genetic disorder causing insensitivity to androgens in a person with female phenotype and 46,XY karyotype due to a mutation in the androgen receptor gene located on chromosome X. These children are born with female external genitalia, and females are transmitters. CASE REPORT: We illustrate an unexpected diagnosis of CAIS in two siblings during examination for short stature, and describe transmission/carriers in the family along with ethical aspects. CONCLUSION: A genetic examination could have earlier revealed the transmission of c.2495G>Tp.(Arg832Leu) mutation in exon 7. Our experience highlights the possibility of prenatal testing for the management of pregnancy in a family with a history of CAIS. The implications of prenatal testing in relation to CAIS with clearer explication of ethical and clinical issues warrant further investigation.