This paper re-evaluates how effectively regular colonoscopy protects people with Lynch syndrome, a common inherited cause of bowel cancer. While colonoscopy saves lives by detecting cancers at an early stage, large contemporary studies show it does not reliably prevent cancers from developing. This is because Lynch syndrome cancers can grow rapidly or arise without visible […]
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Remembering Dr. Robert Sladek
A few days ago, I learned the sad news that Dr. Robert Sladek had passed away. Although our paths crossed only a few times in life and in academia, he left a deep impression on me. Dr. Robert Sladek was one of those rare individuals whose intellect and scholarly rigor were evident even in a […]
Multi-tissue analysis improves diagnosis of mosaicism in tumour predisposition syndromes
Tumour predisposition syndromes are typically diagnosed through blood-based genetic testing. However, pathogenic variants arising early in embryonic development may lead to mosaicism that escapes detection in blood. A recent JMG study shows that analysing multiple tissues can uncover these hidden variants and confirm the underlying genetic diagnosis. Multi-tissue analysis can therefore shorten diagnostic odysseys, improve […]
MGRN1 is linked to recessive heart and laterality defects: the first genotype-phenotype report in humans (Contributed by Laura Kasak)
This study identified a novel gene – MGRN1 (mahogunin ring finger 1) – implicated in congenital fetal malformations. A family experienced two pregnancies with fetuses presenting unexplained severe heart and laterality defects. ‘Genomic autopsy’ of affected cases uncovered a rare homozygous defect in MGRN1, regulating early development and left-right patterning. The observed human malformations closely resembled developmental […]
Clinically significant DNA variation from the GENCOV and HostSeq COVID-19 genome sequencing studies (Contributed by Erika Frangione)
Large-scale Canadian genome research studies like HostSeq provide researchers with an opportunity to study genetic variation in the Canadian population. Sharing this data with public databases such as ClinVar is important for advancing our understanding of genetic changes associated with disease risk and susceptibility. However, these databases are often incomplete or contain conflicting information. By […]
Inherited variants in autosomal dominant disease genes are a significant cause of fetal structural anomalies
In a cohort of 1,185 fetuses with structural anomalies undergoing prenatal exome sequencing, inherited variants in autosomal dominant disease genes accounted for 11.5% of diagnoses and conferred a recurrence risk in nearly one in five families. Often overlooked by standard filtering strategies, these findings have important implications for genetic counselling, parental assessment and the design […]
Evaluating the efficiency of nanopore adaptive sampling sequencing in detecting balanced translocation (Contributed by Meng Gao)
Some people carry a “balanced translocation,” a harmless-looking chromosome change that can greatly increase the risk of recurrent miscarriage or having affected children. Unfortunately, many of these changes are too small or too complex to be detected by routine genetic tests. In this study, we evaluated a targeted DNA sequencing approach called nanopore adaptive sampling […]
End of a diagnostic odyssey: the added value of multi-tissue analysis in the identification of mosaicism in tumour predisposition syndromes (Contributed by Dr. Layla Damen)
People with a tumor predisposition syndrome have increased risks of various tumors. The cause is an inherited mutation in a certain gene, usually detected with a DNA-test using blood. Sometimes a novel mutation develops during early embryonic development. The mutation is then not present in all cells, which is called mosaicism. In mosaicism, a blood […]
Mosaic variegated aneuploidy as a novel feature in patients with Mulibrey nanism and TRIM37 variants (Contributed by Dr Anna H Hakonen)
This study reveals new information on the disease mechanisms of a hereditary condition called Mulibrey nanism. Mulibrey nanism occurs if a child inherits a genetic change in a gene called TRIM37 from both parents (recessive inheritance). Children and adults with Mulibrey nanism are shorter than average, they may develop a rare type of heart disease, […]
Reasoning Based AI in Rare Disease Diagnosis
A recent study in Nature marks a conceptual advance in medical genetics by reframing rare disease diagnosis as a coordinated reasoning task rather than a static prediction problem. The proposed agentic system orchestrates phenotype, genotype, and knowledge retrieval modules under a large language model host, generating ranked hypotheses with transparent, evidence linked logic. It is […]