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. […]
Latest articles
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; […]
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 […]
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 […]
Complex pathway to identification of Fanconi anaemia due to biallelic BRCA2 variants presenting as severe chemotherapy toxicity in adulthood
We describe an interesting case of a 23 year old female with known primary ovarian failure, who was diagnosed with abdominal adenocarcinoma of gastrointestinal origin. She experienced severe and prolonged chemotherapy side effects, and was eventually diagnosed with Fanconi anaemia due to biallelic BRCA2 variants. We highlights hurdles that were encountered during diagnosis, including initial […]
SUFU haploinsufficiency causes a recognisable neurodevelopmental phenotype at the mild end of the Joubert syndrome spectrum
Joubert syndrome (JS) is a genetic neurodevelopmental condition diagnosed by characteristic brain imaging findings in patients with abnormal eye movements, ataxia, and cognitive impairment. Until recently, all JS patients have been consistent with autosomal or X-linked recessive inheritance of variants in one of >40 ciliary genes. This study and other recent work demonstrate that dominant […]
NOTCH2NLC-related disorders: the widening spectrum and genotype–phenotype correlation
GGC repeats in the NOTCH2NLC has been identified in patients with a group of neurodegenerative disorders. We review the NOTCH2NLC-related disorders and potential disease-causing mechanisms. We found that visual abnormalities may be NOTCH2NLC-specific, and the actual prevalence of the expansion in European patients may be potentially higher than reported. Repeat size and interruptions confer pleiotropic […]
SOX10: twenty years of phenotypic plurality and current understanding of its developmental function
SOX10 is a transcription factor involved in development of the neural crest and of a few non-neural crest derivatives. It has been involved in human disease (Waardenburg-Hirschsprung disease; type 4 Waardenbur syndrome) in 1998. Since then, the phenotypic spectrum has been broadened several times and now goes from mild to life-threatening phenotype. In this review, […]
Sporadic facial angiofibroma and sporadic angiomyolipoma mimicking Tuberous Sclerosis Complex
Tuberous Sclerosis Complex (TSC) is due to TSC1/TSC2 mutations, leading to the development of tumors in multiple organs. Here, we describe an individual with minimal TSC clinical features for whom we identified four different inactivating TSC2 mutations, including two unique mutations in each of angiomyolipoma and angiofibroma tumors; these mutations were not present at all in other analyzed tissues. This suggests […]
Biallelic variants in ZFP36L2 cause female infertility characterized by recurrent preimplantation embryo arrest
Recurrent preimplantation embryo developmental arrest (RPEA) is the most common cause of assisted reproductive technology failure though the causes remain unknown. This study emphasizes the relevance of the association between maternal mRNA decay and human preimplantation embryo development. A novel potential gene ZFP36L2 was identified as a factor associated with female infertility characterized as RPEA. […]