European Union's Seventh Framework programme.

This is the first study performed in Murcia (south-eastern Spain) in which 592 families with hereditary breast and ovarian cancer were identified thanks to Genetic Counselling Units from this area over 6 years. Diagnostic performance was 18.1% and 194 different genetic variants were obtained. Variants with uncertain significance accounted for only 5.6% of the total number of reports, so our population has been well characterised. In BRCA1 gene, two novel variants were found (c.1859delT and c.3205C > T) and the most frequently detected mutations were c.68_69delAG, c.212 + 1G > A, c.5123C > A, c.211A > G and c.1918C > T, which together represented 56.67% of total pathogenic mutations. In BRCA2 gene, four recurrent variants were described (deletion of entire exon 2, c.9117G > A, c.3264dupT and c.3455T > G) representing 43.5% of the mutations in this gene. Mutation c.68_69delAG and deletion of entire exon 2 in BRCA1 and BRCA2 genes respectively were the most prevalent variants in our population. Regarding the genotype-phenotype relation, mutation c.212 + 1G > A appeared in an important percentage of breast and ovarian cancer cases, c.5123C > A in bilateral breast cancer and c.9117G > A in bilateral breast cancer and ovarian cancer. With respect to clinical-pathological characteristic, BRCA1/BRCA2 mutation carriers showed earlier onset age of breast tumour and higher risk of developing contra lateral breast cancer than non-informative cases. Moreover, association between either molecular subtype triple negative breast cancer or ovarian cancer and BRCA1 carriers was obtained.

Group A streptococcal (GAS) disease shows increasing incidence worldwide. We characterised children admitted with GAS infection to European hospitals and studied risk factors for severity and disability. This is a prospective, multicentre, cohort study (embedded in EUCLIDS and the Swiss Pediatric Sepsis Study) including 320 children, aged 1 month to 18 years, admitted with GAS infection to 41 hospitals in 6 European countries from 2012 to 2016. Demographic, clinical, microbiological and outcome data were collected. A total of 195 (61%) patients had sepsis. Two hundred thirty-six (74%) patients had GAS detected from a normally sterile site. The most common infection sites were the lower respiratory tract (LRTI) (22%), skin and soft tissue (SSTI) (23%) and bone and joint (19%). Compared to patients not admitted to PICU, patients admitted to PICU more commonly had LRTI (39 vs 8%), infection without a focus (22 vs 8%) and intracranial infection (9 vs 3%); less commonly had SSTI and bone and joint infections ( p < 0.001); and were younger (median 40 (IQR 21–83) vs 56 (IQR 36–85) months, p = 0.01). Six PICU patients (2%) died. Sequelae at discharge from hospital were largely limited to patients admitted to PICU (29 vs 3%, p < 0.001; 12% overall) and included neurodisability, amputation, skin grafts, hearing loss and need for surgery. More patients were recruited in winter and spring ( p < 0.001). Conclusion : In an era of observed marked reduction in vaccine-preventable infections, GAS infection requiring hospital admission is still associated with significant severe disease in younger children, and short- and long-term morbidity. Further advances are required in the prevention and early recognition of GAS disease. What is Known: • Despite temporal and geographical variability, there is an increase of incidence of infection with group A streptococci. However, data on the epidemiology of group A streptococcal infections in European children is limited. What is New: • In a large, prospective cohort of children with community-acquired bacterial infection requiring hospitalisation in Europe, GAS was the most frequent pathogen, with 12% disability at discharge, and 2% mortality in patients with GAS infection. • In children with GAS sepsis, IVIG was used in only 4.6% of patients and clindamycin in 29% of patients. Supplementary Information The online version contains supplementary material available at 10.1007/s00431-022-04718-y.

In the original published version of the above article, the names of members of the EUCLIDS consortium were not introduced in the authorship section. The names are now properly displayed.The original article has been corrected.Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

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Mutations in breast cancer susceptibility (BRCA) genes lead to defects in DNA repair processes resulting in elevated genome instability and predisposing to breast and ovarian cancer. We report a novel mutation (c.1918C>T) in the exon 11 of the BRCA1 gene that consists of a nonsense mutation that causes a stop codon downstream in the 640 position of the protein. The mutation was present in two Spanish unrelated families and was associated with four breast cancer cases, including two bilateral breast cancer (one of them synchronous). The median age/mean age (range) was 48.5/44.25 years (27-53). This finding led us to perform haplotype analysis in all family carriers. Four highly polymorphic microsatellite markers were used (17-3858, 17-3930, D17S855, D17S1326) to establish whether or not all these families had a common ancestor. This analysis showed that all mutation carriers of these families had a common haplotype. None of the noncarriers of the mutation or of the 24 healthy controls showed this haplotype. Therefore, the c.1918C>T mutation carriers from these two families allows us to assert that all analyzed mutation carriers share a common ancestry.

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