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 […]
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 […]
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 […]
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 […]
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 […]
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 […]
Pharmacogenomic testing and prescribing patterns for cancer patients in a large national precision medicine cohort
Analyzing large cancer populations could help both patients and providers better understand current prescribing and genetic testing practices for precision medicine. In this study, we analyzed cancer patients, precision medicine drugs, and related genetic testing in the National Institutes of Health “All of Us” healthcare research database. While cancer patients frequently received precision medicine drugs, […]
Clinical and molecular features of 66 patients with musculocontractural Ehlers−Danlos syndrome caused by pathogenic variants in CHST14 (mcEDS-CHST14)
Musculocontractural Ehlers−Danlos syndrome (mcEDS) is caused by biallelic loss-of-function variants in CHST14 (mcEDS-CHST14) or DSE. To reveal the spectrum of variants, prevalence of various manifestations, and natural history of mcEDS-CHST14, we collected and evaluated detailed and comprehensive clinical and molecular information on 66 patients through international collaborations. Craniofacial, skeletal, cutaneous, and ocular features were common. […]
Variable skeletal phenotypes associated with biallelic variants in PRKG2
Although disruption of PRKG2 has been shown to cause skeletal anomalies and/or dwarfism in rodents, cattle and dogs, only two human patients have been reported in the medical literature so far. In this study, four individuals with rare PRKG2 variants are described. In one family, the variant lies close to the end of the gene; […]