Hypermobile Ehlers-Danlos syndrome (hEDS) phenotype in fragile X premutation carriers: case series

Although hypermobile Ehlers-Danlos syndrome (hEDS) is the most common type of EDS, its genetic etiology is unclear. This study presents 5 cases who had both a hEDS phenotype and FMR1 premutation. In premutation carriers, a possible connection between both conditions could be explained by a depletion of fragile X mental retardation protein (FMRP), a major […]

Read More…

Prevalence and spectrum of DNA mismatch repair gene variation in the general Chinese population

DNA mismatch repair (MMR) genes of MLH1, MSH2, MSH6 and PMS2 play essential roles in maintaining microsatellite stability through DNA mismatch repair, pathogenic variation in MMR genes causes microsatellite instability and high cancer risk as represented by the Lynch syndrome. We identified 17,687 MMR variants from 18,844 ethnic Chinese individuals. We characterized the basic biological […]

Read More…

Loss-of-function variants in DNM1 cause a specific form of developmental and epileptic encephalopathy only in bi-allelic state

The DNM1 gene encodes dynamin-1, a protein playing an important role in signal transduction from one neuron to another. This neuronal communication uses release of neurotransmitters stored in vesicles beneath the neuronal membrane. Dynamin-1 induces membrane constriction subsequently resulting in vesicle fission from the membrane. Missense variants in DNM1 were found to be associated with […]

Read More…

Adult phenotype of KCNQ2 encephalopathy

In this study, we describe the disease evolution and adult phenotype of KCNQ2 encephalopathy through retrospective study of 13 patients (18-45 years of age). We show that┬áseizure frequency declines over the years and that most patients are seizure-free in adulthood. Longer seizure-free periods followed by seizure recurrence are however common during childhood and adolescence.┬áTonic seizures […]

Read More…

Learning from massive testing of mitochondrial disorders: UPD explaining unorthodox transmission

Reaching a full genetic diagnosis in patients with rare diseases such as the mitochondrial disorders (MDs) is important for counseling and to prepare correct follow up and future therapies. Massive gene sequencing allow extensive investigation of potential etiologies but it is important to consider uniparental disomy (UPD) as a possible explanation for the transmission whenever […]

Read More…

A protein-truncating mutation in CCNB3 in a patient with recurrent miscarriages and failure of meiosis I

Our patient suffered from 16 miscarriages and spent more than 20 years looking for treatments that could allow her to have live births but without success. She changed countries, cities, and medical centers, and sought the help of the best specialists but with no cure or satisfying answers. Her desire to understand the causes of […]

Read More…

WFS1 protein expression correlates with clinical progression of optic atrophy in patients with Wolfram syndrome

Wolfram syndrome, a rare form of monogenic diabetes and neurodegeneration, currently has no cure or treatment to slow the progression. Currently we have no way of predicting progression to blindness, or how different genetic mutations may affect this progression. This paper shows that affected people who retain partial Wolfram protein expression, present with milder visual […]

Read More…

Neurodevelopmental phenotypes associated with pathogenic variants in SLC6A1

SLC6A1 encodes GAT-1, a gamma-aminobutyric acid (GABA) transporter in the brain. We describe 28 individuals recruited through Simons Searchlight with heterozygous pathogenic or likely pathogenic SLC6A1 variants to better understand the associated neurobehavioral phenotype. Individuals all have some combination of developmental delay, intellectual disability, speech delay, language disorder, seizures, autism, hypotonia, and/or movement/coordination disorders. We […]

Read More…

Development and evaluation of an online, patient-driven, family outreach intervention to facilitate sharing of genetic risk information in families with Lynch syndrome

Cancer patients with a genetic mutation for hereditary cancer are largely responsible for sharing genetic risk information with relatives and encouraging them to have predictive genetic testing. Genetic risk communication within families is incomplete and limited to close relatives. To address this gap, we developed FamilyCONNECT, a provider-mediated, patient-navigated online tool to facilitate family outreach […]

Read More…

Genetic testing in motor neuron disease and frontotemporal dementia: a 5-year multicentre evaluation

Motor neurone disease (MND) is a neurodegenerative disorder that forms a disease spectrum with frontotemporal dementia (FTD). Affected MND/FTD patients and their unaffected relatives are often referred to clinical genetics for genetic testing. Our service evaluation explored genetics testing practices over a five-year period and across ten UK genetics centres. 301 referrals were included, 70 […]

Read More…