Long term dormancy in a BRCA1 heterozygote

Germline pathogenic variants in BRCA1 or BRCA2 genes increase the risk of ovarian high grade serous carcinoma, the most common and most lethal subtype of epithelial ovarian cancer. Carriers of these genetic variants are usually offered surgery known as risk-reducing salpingo-oophorectomy (RRSO) where the Fallopian tubes and ovaries are removed. We report the case of […]

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CDH1 germline mutations in healthy individuals from families with the hereditary diffuse gastric cancer syndrome

Hereditary diffuse gastric cancer is an inherited cancer predisposition syndrome associated with CDH1 germline mutations. To date, more than 500 mutations are described from different countries, with a particular higher mutation frequency in countries with low incidence for gastric cancer. The distribution of germline mutations sub-types in this inherited cancer susceptibility is rather heterogeneous: missense […]

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Impaired social cognition and fine dexterity in patients with Cowden syndrome associated with germline PTEN variants

Cowden syndrome is a genetic disorder related to germline PTEN variants and characterized by increased risk of cancers. These patients sometimes show behaviors considered as maladapted to social norms and conventions. We collected data on 15 patients from a single center in France. We analyzed their abilities in social cognition, considered as cognitive processes involved […]

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Multimodal bioinformatic analyses of the neurodegenerative disease-associated TECPR2 gene reveal its diverse roles

Loss of TECPR2 function has been implicated in an array of neurodegenerative diseases, but what exactly is that function? Understanding TECPR2 function is essential for developing precision diagnostics and targeted treatment options for TECPR2-related neurodegenerative diseases. Therefore, we leveraged the increasing amounts of functional genomic data to perform a first comprehensive functional characterization of TECPR2. We report that TECPR2 might […]

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Surprising genetic and pathological findings in a patient with giant bilateral periadrenal tumors: PEComas and mutations of PTCH1 in Gorlin-Goltz syndrome

The genetic background of a previously undescribed manifestation in a Gorlin-Goltz syndrome (including skin basal cell carcinomas and multiple developmental abnormalities) patient is presented: two-sided PEComas (perivascular epitheloid cell tumors) next to the adrenal glands. A novel germ-line mutation of the PTCH1 tumor suppressor gene was identified. Surprisingly, the same somatic mutation (a five nucleotide […]

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Redefining WILD syndrome: a primary lymphatic dysplasia with congenital multisegmental lymphoedema, cutaneous lymphovascular malformation, CD4 lymphopaenia and warts

Swelling of the extremities (lymphoedema) due to underlying abnormalities of the lymphatic system has many causes but can be genetic. We describe 20 patients with a newly defined clinical entity called WILD syndrome (acronym from Warts, Immunodeficiency and Lymphatic Dysplasia). They presented with asymmetrical lymphoedema affecting different body regions including internal organs. Low immunity was […]

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Loeys-Dietz and Shprintzen-Goldberg Syndromes: analysis of TGF-β-opathies with craniofacial manifestations using an innovative multi-modality method

Loeys-Dietz and Shprintzen-Goldberg syndromes are caused by mutations along the TGF-beta signaling pathway.  Some of the most striking features include craniofacial anomalies.  Yet it is very difficult to find a common facial pattern that can be matched to the specific mutation.  We used deep clinical examination methods and cutting-edge imaging technology, such as 3D photos […]

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New locus underlying familial adenomatous polyposis: 3.9 MB rearrangement disrupting APC expression

Familial adenomatous polyposis (FAP) is a cancer predisposition syndrome caused by changes in the APC gene, but approximately 20% of patients remain unsolved after routine diagnostics. In this work, we applied multidimensional genomic analyses to solve a case of FAP after more than 20 years. We identified a complex genomic rearrangement disrupting several coding genes […]

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Biallelic ANGPT2 loss-of-function causes severe early onset nonimmune hydrops fetalis

Variants in the angiopoietin 2 (ANGPT2) gene were recently shown to cause lymphedema in children and adults by dominant inheritance. In a single family that experienced recurrent pregnancy loss due to severe generalized swelling of the fetuses (hydrops fetalis), we identified a novel disorder caused by bi-allelic variants in the ANGPT2 gene. Angiopoietin 2 is […]

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Phenotypic spectrum and clinical course of single large-scale mitochondrial DNA deletion disease in the paediatric population: a multicentre study

Large-scale mitochondrial DNA deletions are one of the most common causes of mitochondrial disease. The presentation varies greatly and understanding of the disease course has remained unclear. This large study of 80 patients with disease onset in childhood provides a detailed and improved insight into the characteristic symptoms, signs and course of the disease. It […]

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