Québec offers a striking example of how human migration leaves a genetic record. A relatively small number of French settlers founded communities along the St. Lawrence River, followed by later migrations into Charlevoix and Saguenay–Lac-Saint-Jean. These population expansions produced regional founder effects and genetic drift, increasing the frequency of some rare variants. One well-known example […]
Latest articles
A rare non-coding variant is genetically associated with early onset severe retinal degeneration (Contributed by Dr. Philipp Maass)
In a family where the parents were relatives, three children developed a severe degeneration of the retina, leading to blindness in childhood. To investigate this, we searched their DNA and found a single misspelled letter, inherited from both parents. This DNA variation sits on a switch that regulates genes. Using CRISPR genome editing, we found […]
Navigating the Complexity of BRCA1/BRCA2 Constitutional Mosaicism: A Case Report and Literature Review Exploring Clinical, Molecular, and Genetic Counselling Approaches (Contributed by Dr Valeria Viassolo)
Pathogenic variants in BRCA1 and BRCA2 genes increase a person’s risk of developing cancer, particularly breast and ovarian cancer. These variants are usually inherited from a parent and are present in all cells of the body. In rare cases, the genetic change occurs during early embryonic development and is present in only a subset of […]
Exome sequencing and large-scale analysis of electronic medical record-linked biobank data identify candidate deafness genes (Contributed by Professor Karen B Avraham)
Hearing loss is often caused by genetic variants, but for many people, the underlying cause remains unknown, preventing an accurate diagnosis and limiting access to emerging genetic therapies. We performed whole-exome sequencing in more than 1,000 people with hearing loss and integrated the findings with data from their electronic medical records. Despite incomplete clinical information, […]
Founder derivative chromosome causing a recessive-like recurrent disorder: der(17)-associated 19p13.3 duplication in the Upper Tigris Basin (Contributed by Dr. Murat Ozturk)
In this study, we identified the same rare chromosome rearrangement in 15 affected individuals from 11 unrelated families in the Upper Tigris Basin. The rearrangement causes the gain of a small segment of chromosome 19 and the loss of a segment of chromosome 17, resulting in a recognizable pattern of developmental, neurological, and growth-related features. […]
Dual impact of uniparental disomy in imprinting and recessive disorders: a case of UPD(15) with unexpected inheritance and literature review (Contributed by Dr. Sarah Baer)
Our study highlights an unusual way in which one genetic event can cause two different rare diseases in the same child. We describe a boy with Prader-Willi syndrome and Tay-Sachs disease resulting from the inheritance of both copies of chromosome 15 from his mother. Reviewing previous cases showed that similar combinations of genetic diseases can […]
Deletion size and background genetic variation shape congenital heart disease phenotypes in 3016 individuals with 22q11.2 deletion syndrome (Contributed by Dr. Bernice E Morrow)
The clinical presentation of 22q11.2 deletion syndrome (22q11.2DS) is highly variable due to reasons that are not fully understood. Most, but not all, individuals are affected with various types of congenital heart disease (CHD). In our study, we performed a retrospective analysis of data from 3,016 individuals with 22q11.2DS to identify demographic and/or genomic contributors […]
Integrating deep-exome sequencing and droplet digital PCR for genetic diagnosis of 142 patients with somatic overgrowth and vascular malformation (Contributed by Mrs. Karin Sollander)
In this study, we show how it’s possible to increase the diagnostic yield and improve outcome for patients with somatic overgrowth and vascular malformations. These conditions are often caused by genetic variants in a fraction of the individual’s cells, so called mosaicism. Low fraction variants make diagnostics challenging and requires specific laboratory methods. Identifying variants […]
Recurrent helical COL1A1 E678K variant in three families with an EDS-predominant phenotype expanding the clinical and molecular spectrum of COL1-related overlap disorder (Contributed by Dr Shaimaa Helal)
Type I collagen helps give connective tissues their strength. Changes in COL1A1, a gene involved in making this collagen, can cause conditions affecting bones, joints and skin. We describe seven people from three unrelated families with the same COL1A1 variant. They had flexible joints, soft skin and, in some cases, hip dysplasia or dislocation present […]
Clinicopathological, imaging and genetic spectrum of inherited rimmed vacuolar myopathies in a Chinese cohort (Contributed by Dr Feng Lin)
Rimmed vacuoles are small abnormal spaces seen in muscle fibers, but they can occur in many inherited muscle diseases, making diagnosis difficult. We studied 48 patients in China by combining symptoms, muscle imaging, biopsy findings and genetic testing. A genetic diagnosis was reached in 42 patients (87.5%), involving 16 different disease-causing genes. Importantly, rimmed vacuoles […]