Parkinson’s disease (PD) is a complex neurodegenerative disorder. Several risk variants and genes were identified by genetic studies and predictive disease risk models were built based on associations with common variants. We showed that singleton loss-of-function variants contribute to the genetic architecture of PD and that disease risk prediction models combining singleton and common variants […]
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CDK5RAP2 primary microcephaly is associated with hypothalamic, retinal and cochlear developmental defects
Primary Microcephaly (PM) is a neurodevelopmental disorder characterized by a small brain size frequently associated with intellectual disability. CDK5RAP2 is a cyclin-dependent kinase regulatory subunit associated protein whose deficiency causes a rare recessive isolated PM called MCPH3. In this article, Nasser and colleagues report patients carrying new bi-allelic CDK5RAP2 mutations and found that all patients […]
ATR-16 syndrome: mechanisms linking monosomy to phenotype
Advances in DNA sequencing technology mean chromosomal deletions are increasingly found in healthy individuals and also in patients with a wide range of developmental abnormalities. Understanding the contribution of each deletion to the clinical picture is challenging. In this work, as an example of this common phenomenon, we analysed 41 patients with simple deletions of […]
Whole genome sequence-based haplotypes reveal a single origin of the 1393 bp HBB deletion
Germline mutations of HBB gene that reduces its expression give rise to b thalassemia, and nearly 300 of these have been described. Deletions causing b-thalassemia are very rare. We have identified three individuals with identical HBB deletions of 1,393 bp associated with relatively high levels of hemoglobin A2 and hemoglobin. Using information from whole genome […]
Impacts of genomics on the health and social costs of intellectual disability
The economic cost of caring for people with intellectual disability (ID) is extremely high for families, health systems and society. These costs have been significantly underestimated. We show that when all costs of care for a person with ID are considered, that they average US$172,000 per person per year, accumulating to millions of dollars over […]
Xq28 copy number gain causing moyamoya disease and a novel moyamoya syndrome
Moyamoya angiopathy is a rare cerebrovascular disorder. Its main clinical manifestations include ischemic and hemorrhagic stroke. A few genes and cytogenetic anomalies have been reported in a limited number of patients. However, the molecular causative anomaly is so far unknown in most moyamoya patients. In this study, we identified a novel association between an Xq28 […]
FLNC truncations cause arrhythmogenic right ventricular cardiomyopathy
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a heart muscle disease that affects predominantly the right ventricle and cause sudden cardiac death. We studied 156 ARVC patients lacking variants in known ARVC genes, and identified two unique FLNCtv variants in two families fulfilling “definite” diagnosis according to the 2010 ARVC Task Force Criteria. Segregation analysis revealed […]
Increased TBX6 Gene Dosages Induce Congenital Cervical Vertebral Malformations in Humans and Mice
We previously reported that the human 16p11.2 BP4-BP5 deletion and its associated TBX6 dosage reduction caused congenital vertebral malformations (CVMs) in thoracic and lumber vertebrae. Here we reveal genetic contributions of the reciprocal 16p11.2 BP4-BP5 duplication to cervical CVMs. The spinal assessments in seven duplication carriers showed that four presented characteristics of cervical CVMs. We […]
Gene editing prospects for treating inherited retinal diseases
Retinal diseases can result from genetic mutations or combined risk factors, all causing vision impairment progressing to blindness. To date, available therapeutic approaches result in inefficient and expensive treatments. The CRISPR-Cas9 system, an RNA-guided genome editing technology, may be applied to precisely correct or remove disease-related genetic mutations, or induce permanent inhibition of factors promoting […]
Genetic variability and potential effects on clinical trial outcomes: perspectives in Parkinson’s disease
All clinical trials for drugs aimed to stop diseases such as Parkinson’s disease and Alzheimer’s disease have failed, and currently there are no drugs that can stop or slow down these diseases. In parallel, we have gathered a lot of data on how genetics affect the risk for these diseases and their clinical progression. However, […]