A 16-year-old boy developed multiple rare skin tumours called atypical cutaneous fibrous histiocytomas (ACFHs). Genetic testing revealed he has two inherited cancer predisposition conditions: Li-Fraumeni syndrome (TP53 gene) and Birt-Hogg-Dubé syndrome (FLCN gene), a rare combination known as MINAS. His TP53 mutation was new (not inherited), while the FLCN mutation came from his father. This […]
Latest articles
Long-term efficacy of migalastat in females with Fabry disease
Females with Fabry disease often experience diagnostic delays and underappreciated disease burden due to variable disease presentation and progression. The spectrum of disease severity and long-term efficacy of migalastat were assessed in females with Fabry disease and amenable GLA variants. Most had multiorgan involvement at baseline, suggesting significant disease burden. Migalastat treatment preserved renal function, […]
APC I1307K and clinical management: insights from UK Biobank association analysis of colorectal and other cancer risks in Ashkenazi and non-Ashkenazi whites
The APC I1307K variant, more common in Ashkenazi Jewish (AJ) individuals, has been linked to a modest increase in colorectal cancer (CRC) risk. Analysis of over 460,000 UK Biobank participants found no statistically significant association between I1307K and CRC—or other cancers—in AJ or non-AJ white populations. However, the analysis was underpowered due to the variant’s […]
Resolving structural variations missed by short-read sequencing uncovers their pathogenicity
Short-read Genome sequencing (sr-GS) affords efficient characterization of apparently balanced chromosomal rearrangement. However, 9 to 11% of cases remain undetectable, mainly due to highly repetitive genomic regions at breakpoints. We studied 14 patients with abnormal phenotype carrying ABCR that could not be detected by sr-GS. We used a combination of different approaches including fluorescence in […]
Development of a functional assay for the characterisation of SMAD4 variants from the French haemorrhagic hereditary telangiectasia cohort
Hereditary Hemorrhagic Telangiectasia (HHT) and Juvenile Polyposis Syndrome (JPS) can be caused by deleterious variants in the SMAD4 gene, which is part of the TGFß/BMP signaling pathway. We developed a functional assay for SMAD4 variants that allows discrimination between benign and pathogenic SMAD4 variants. We found that all the variants tested led to a loss of function in the SMAD4 protein. […]
First intragenic inversion of CYP11B1 gene causing 11β-hydroxylase deficiency: a molecular diagnosis easily overlooked
Steroid hormones are essential for the body to function properly. 11beta-hydroxylase deficiency is a rare genetic disorder that disrupts the production of steroid hormones. We have studied a patient with this deficiency and have identified a structural anomaly in the CYP11B1 gene in this family, which is particularly complicated to identify: the region of the […]
Homologous recombination deficiency in unselected high-grade ovarian carcinoma
1008 women with high-grade ovarian carcinoma (serous, endometrioid, clear cell, carcinosarcoma) were tested for pathogenic variants (PV) in germline homologous recombination repair (HRR) genes and tumour homologous recombination deficiency (HRD) including tumour BRCA1/2 and genomic instability (GI). Over 95% of tumours with a BRCA1 PV had High GI, whilst only 80% with a BRCA2 PV […]
New patients with duplication of the pituitary gland–plus syndrome, including a PTCH2 variant and a literature review
Duplication of the Pituitary Gland Plus Syndrome is an extremely rare condition, with fewer than 60 cases reported worldwide. It involves having two pituitary glands, abnormal neck bones, cleft palate, and a teratoma (benign tumor) inside the mouth at birth—features that suggest a genetic cause rather than occurring by chance. We report the first two […]
Exploration of possible association of BRIP1 pathogenic variants with central nervous system cancers in an institutional cohort
Our study examines a potential link between BRIP1 pathogenic germline variants (PGVs) and central nervous system (CNS) tumors through a retrospective review of institutional germline and somatic databases. We found that 16.3% of families with BRIP1 PGVs reported CNS tumors. Somatic BRIP1 variants were rare in CNS tumors, but one of two individuals subsequently germline […]
Refined genotype–phenotype correlations in neurofibromatosis type 1 patients with NF1 point variants
Neurofibromatosis type 1 (NF1) is a genetic condition that can cause a wide range of medical issues, with symptoms varying greatly between individuals. In this study, we analyzed over 100 patients with specific NF1 gene mutations and found that some of these variants are consistently associated with milder or more severe forms of the disease. […]