Ovarian cancer (OC) is the deadliest gynecologic malignancy with a substantial proportion of hereditary cases and a frequent association with breast cancer (BC). Genetic testing facilitates treatment ...and preventive strategies reducing OC mortality in mutation carriers. However, the prevalence of germline mutations varies among populations and many rarely mutated OC predisposition genes remain to be identified. We aimed to analyze 219 genes in 1333 Czech OC patients and 2278 population-matched controls using next-generation sequencing. We revealed germline mutations in 18 OC/BC predisposition genes in 32.0% of patients and in 2.5% of controls. Mutations in
,
,
, and mismatch repair genes conferred high OC risk (OR > 5). Mutations in
and
were associated with moderate risk (both OR = 3.5).
mutations dominated in almost all clinicopathological subgroups including sporadic borderline tumors of ovary (BTO). Analysis of remaining 201 genes revealed somatic mosaics in
and germline mutations in
and
associating with a high/moderate OC risk significantly; however, further studies are warranted to delineate their contribution to OC development in other populations. Our findings demonstrate the high proportion of patients with hereditary OC in Slavic population justifying genetic testing in all patients with OC, including BTO.
Romani people have a high prevalence of kidney failure. This study examined a Romani cohort for pathogenic variants in the
, and
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.
The study included 57 Romani from different families with clinical features that suggested AS who underwent next-generation sequencing (NGS) of the
genes, and 83 family members.
In total, 27 Romani (19%) had autosomal recessive AS caused by a homozygous pathogenic c.1598G>A, p.Gly533Asp variant in
(
= 20) or a homozygous c.415G>C, p.Gly139Arg variant in
(
= 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 (
= 0.023), three (50%) had end-stage kidney failure by a median age of 42 years (
= 0.653), and five (83%) had hearing loss (
= 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%).
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.
Hepatoblastoma is an uncommon malignant neoplasm in general, yet, it is the most common liver malignancy in children with the incidence about one per milion children. This type of liver tumor usually ...occurs before the age of three years. The etiology of hepatoblastoma remains unknown. However, there are some genetic conditions known to be associated with an increased risk of developing hepatoblastoma such as Beckwith-Wiedemann syndrome, hemihypertrophy, APC-associated polyposis, α-1-antitrypsin defficiency and some metabolic disorders including tyrosinemia, galactosemia and glycogen storage disease type 1. There is a higher risk of hepatoblastoma in children with very low birthweight, children who acquire hepatitis B at an early age and children with congenital biliary atresia.
Two Gram-stain-positive, coagulase-negative staphylococcal strains were isolated from abiotic sources comprising stone fragments and sandy soil in James Ross Island, Antarctica. Here, we describe ...properties of a novel species of the genus
that has a 16S rRNA gene sequence nearly identical to that of
However, compared to
and the next closest relatives, the new species demonstrates considerable phylogenetic distance at the whole-genome level, with an average nucleotide identity of <85% and inferred DNA-DNA hybridization of <30%. It forms a separate branch in the
phylogenetic clade as confirmed by multilocus sequence analysis of six housekeeping genes,
,
,
,
,
, and
Matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS) and key biochemical characteristics allowed these bacteria to be distinguished from their nearest phylogenetic neighbors. In contrast to
subsp.
, the novel strains are pyrrolidonyl arylamidase and β-glucuronidase positive and β-galactosidase negative, nitrate is reduced, and acid produced aerobically from d-mannose. Whole-genome sequencing of the 2.69-Mb large chromosome revealed the presence of a number of mobile genetic elements, including the 27-kb pseudo-staphylococcus cassette chromosome
of strain P5085
(ψSCC
), harboring the
gene, two composite phage-inducible chromosomal islands probably essential to adaptation to extreme environments, and one complete and one defective prophage. Both strains are resistant to penicillin G, ampicillin, ceftazidime, methicillin, cefoxitin, and fosfomycin. We hypothesize that antibiotic resistance might represent an evolutionary advantage against beta-lactam producers, which are common in a polar environment. Based on these results, a novel species of the genus
is described and named
sp. nov. The type strain is P5085
(= CCM 8730
= DSM 104441
).
The description of
sp. nov. enables the comparison of multidrug-resistant staphylococci from human and veterinary sources evolved in the globalized world to their geographically distant relative from the extreme Antarctic environment. Although this new species was not exposed to the pressure of antibiotic treatment in human or veterinary practice, mobile genetic elements carrying antimicrobial resistance genes were found in the genome. The genomic characteristics presented here elucidate the evolutionary relationships in the
genus with a special focus on antimicrobial resistance, pathogenicity, and survival traits. Genes encoded on mobile genetic elements were arranged in unique combinations but retained conserved locations for the integration of mobile genetic elements. These findings point to enormous plasticity of the staphylococcal pangenome, shaped by horizontal gene transfer. Thus,
can act not only as a reservoir of antibiotic resistance in a natural environment but also as a mediator for the spread and evolution of resistance genes.
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