Genetic and metabolic investigations for neurodevelopmental disorders: position statement of the Canadian College of Medical Geneticists (CCMG)

Neurodevelopmental disorders (NDDs) such as global developmental delay, intellectual disability and autism spectrum disorder are collectively the most common chronic medical conditions encountered in pediatric primary care. Given their clinical and etiological heterogeneity, the cause of NDDs can be challenging to diagnose. Guideline recommendations for appropriate metabolic and genomic investigations are inconsistent and has resulted […]

Read More…

Frontotemporal dementia presentation in patients with heterozygous p.H157Y variant of TREM2

This study examined three separate Latin American families with frontotemporal dementia (FTD) and found that they all had the same genetic variation (p.H157Y) in the TREM2 gene. Compared to both sporadic FTD cases and healthy controls, the three patients displayed early behavioral changes, worse cognitive impairments, and more severe brain atrophy, particularly in areas where […]

Read More…

Pseudocoloboma-like maculopathy with biallelic RDH12 missense mutations

RDH12 is an enzyme for recycling visual pigment in the photoreceptor cells. Mutations in RDH12 are known for causing severe childhood-onset visual impairment or diffuse retinal degeneration. This article described a new phenotype, an autosomal recessive pseudocoloboma-like maculopathy, resulting from RDH12 mutations. Although RDH12 is primarily expressed in the photoreceptor cells, relatively normal to subnormal photoreceptor functions are observed […]

Read More…

Biallelic frameshift variants in PHLDB1 cause mild type Osteogenesis Imperfecta with regressive spondylometaphyseal changes

Osteogenesis imperfecta (OI) is a group of disorders, mostly autosomal dominant, inherited characterized by susceptibility to fractures, resulting from a type 1 collagen defect. Although many autosomal recessive genes have been shown to cause OI in recent years, there are still patients whose molecular defect is still unknown. In this study, we described recurrent fractures, […]

Read More…

Genetic diagnosis of Duchenne and Becker muscular dystrophy through mRNA analysis: new splicing events

Duchenne and Becker muscular dystrophy (DMD/BMD), caused by mutations in the DMD gene, are characterized by the presence of progressive muscle weakness. DMD is the most severe form of the disease, leading to significant disability, and is the most common neuromuscular disorder in childhood. For these patients, it is essential to obtain a precise genetic […]

Read More…

Recurring germline mosaicism in a family due to reversion of an inherited derivative chromosome 8 from an 8;21 translocation with interstitial telomeric sequences

Mosaicism (a mixture of normal cells and cells with an abnormal chromosome) is rarely seen in multiple family members. We studied a family spanning three generations that had an abnormal chromosome 8 with a small piece of chromosome 21 attached to its end (der(8)). Multiple family members also had cells with normal chromosomes resulting in […]

Read More…

Long-term multisystemic efficacy of migalastat on Fabry-associated clinical events, including renal, cardiac and cerebrovascular outcomes

Fabry disease is a rare inherited condition that can lead to serious renal, cardiac and cerebrovascular events. Using pooled clinical trial data, we examined the efficacy of migalastat, an oral treatment, in a large group of patients. The rate of newly occurring Fabry-associated clinical events (FACES) with prolonged treatment was low, regardless of whether patients […]

Read More…

FXN gene methylation determines carrier status in Friedreich ataxia

Friedreich ataxia is a genetic condition that is characterized by progressive incoordination and unsteadiness that leads to loss of independent mobility, and premature mortality due to heart disease. It is transmitted by unaffected parents who are “carriers” for the genetic defect that causes Friedreich ataxia, which the child inherits from both parents. Genetic testing of […]

Read More…

Clinical and genetic features of GATOR1 complex-associated epilepsy

We evaluated the mutant prevalence of GATOR1-complex encoded by DEPDC5, NPRL2 and NPRL3 genes, a modulator in mammalian target of rapamycin (mTOR) pathway, in Chinese epilepsy cohort and further defined the phenotype variation. we find that patients carrying DEPDC5-loss-of-function variants may have a high prevalence of focal seizures with a dynamic phenotype highlighting reduced penetrance […]

Read More…

Reporting clinically relevant genetic variants unrelated to genomic test requests: a survey of Australian clinical laboratory policies and practices

A genetic test can identify genetic change(s) not related to the initial reason for doing the test. Internationally, there are differences in how these findings are managed. Survey responses from Australian testing laboratories found that they used several different terms to describe the findings, and had different reasons guiding their decision of whether to report them. […]

Read More…