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 seizure 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. Tonic seizures […]
Latest articles
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 […]
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 […]
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 […]
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 […]
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 […]
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 […]
Analysis of 200,000 exome-sequenced UK Biobank subjects illustrates the contribution of rare genetic variants to hyperlipidaemia
A number of genes have previously been identified in which extremely rare variants with a large impact on gene function can produce marked abnormalities in lipid metabolism. Here we show that much larger numbers of protein-altering variants in these genes can have moderate effects on increasing or reducing the risk of clinically relevant hyperlipidaemia in […]
BBS1 branchpoint variant is associated with non-syndromic retinitis pigmentosa
In our study, we have identified a pathogenic splice defect caused by a branchpoint variant in BBS1 gene in four unrelated individuals with non-syndromic retinitis pigmentosa. Splicing is the process in which the pre-mRNA is transformed into mature mRNA by removing the introns and joining the exons. The branchpoint nucleotide ‘A’, plays a crucial step […]
Haploinsufficiency in non-homologous end joining factor 1 induces ovarian dysfunction in humans and mice
Premature ovarian insufficiency (POI) is a common disease in women that leads to a reduced reproductive lifespan. By utilizing whole-exome sequencing, we identified a rare heterozygous loss-of-function variant of non-homologous end joining factor 1 (NHEJ1) co-segregating with POI in a three-generation Chinese family. The loss-of-function variant caused an approximately 50% reduction in NHEJ1 protein amount […]