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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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, […]

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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. […]

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New locus underlying auriculocondylar syndrome (ARCND): 430 kb duplication involving TWIST1 regulatory elements

We report a novel genetic mechanism underlying Auriculocondylar syndrome (ARCND), a rare disease that mainly affects jaw and outer ear development. In a Brazilian family we identified a large duplication of DNA within the HDAC9 gene that contains elements involved in regulation of the neighbouring gene, TWIST1. We found higher levels of HDAC9 and TWIST1 in […]

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Bi-allelic loss-of-function variants in KIF21A cause severe fetal akinesia with arthrogryposis multiplex

Fetal akinesia (FA) is a multifaceted disease entity, sharing contractures of multiple joints as a common feature. Although progress has been made in defining the environmental and genetic factors involved, in many affected individuals the causes remain unknown. This study identifies bi-allelic pathogenic DNA variants in the kinesin family member 21A gene (KIF21A) as a […]

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