A Deep Intronic Splice Variant in COL1A1 Causing Osteogenesis Imperfecta Type II.

Osteogenesis imperfecta (OI) is a rare disease, hallmarked by bone fragility, multiple fractures, and deformities, and is commonly caused by pathogenic variants in the genes encoding type I collagen. Type II OI is the most severe form and is lethal in the perinatal period. Here, we report recurrence of perinatal lethal OI in two fetuses due to parental mosaicism for a deep intronic pathogenic variant at c.

Clinically Relevant Germline Variants in Children With Nonmedullary Thyroid Cancer.

Context: The underlying genetic cause of nonmedullary thyroid cancer (NMTC) in children is often unknown, hampering both predictive testing of family members and preventive clinical management.

Objective: Our objectives were to investigated the potential heritability in the largest childhood NMTC cohort that has been genotyped to date.

Methods: Nationwide retrospective cohort study in tertiary referral centers.

[A monogenetic disorder instead of type 1 diabetes].

Background: Transient Neonatal Diabetes Mellitus (TNDM) is a rare monogenetic disorder characterized by impaired insulin secretion occurring in the first weeks after birth. TNDM goes into remission after a few weeks to months. However, a large number of children develop non-insulin-dependent DM during puberty.

variant type impacts phenotype and malignancy in pheochromocytoma-paraganglioma.

Background: Traditional genotype-phenotype correlations for the succinate dehydrogenase-complex II (SDH) genes link variants to thoracic-abdominal pheochromocytoma-paraganglioma (PPGL) and variants to head and neck paraganglioma (HNPGL). However, in a recent study we found strong and specific genotype-phenotype associations for variants. In the present study we zoom in on the genotype-phenotype associations of gene variants, considering the impact of individual gene variants on disease risk and risk of malignancy.

Surveillance recommendations for DICER1 pathogenic variant carriers: a report from the SIOPE Host Genome Working Group and CanGene-CanVar Clinical Guideline Working Group.

DICER1 syndrome is a rare genetic disorder that predisposes to a wide spectrum of tumors. Developing surveillance protocols for this syndrome is challenging because uncertainty exists about the clinical efficacy of surveillance, and appraisal of potential benefits and harms vary. In addition, there is increasing evidence that germline DICER1 pathogenic variants are associated with lower penetrance for cancer than previously assumed.