A novel mutation in the matrix metallopeptidase 2 coding gene associated with intrafamilial variability of multicentric osteolysis, nodulosis, and arthropathy.

Background: MONA, which stands for a spectrum of Multicentric Osteolysis, subcutaneous Nodulosis, and Athropathia, is an ultra rare autosomal recessive disorder caused by mutations in the matrix metallopeptidase 2 (MMP2) gene. To date only 44 individuals, carrying 22 different mutations have been reported. Here we report on two brothers with identical homozygous MMP2 gene mutations, but with clearly different phenotypes.

Whole exome sequencing in Finnish families identifies new candidate genes for osteoarthritis.

Introduction: Osteoarthritis (OA) is the most common degenerative joint disease and one of the major causes of disability worldwide. It is a multifactorial disorder with a significant genetic component. The heritability of OA has been estimated to be 60% for hip OA and 39% for knee OA.

Absence of the ER Cation Channel TMEM38B/TRIC-B Disrupts Intracellular Calcium Homeostasis and Dysregulates Collagen Synthesis in Recessive Osteogenesis Imperfecta.

Recessive osteogenesis imperfecta (OI) is caused by defects in proteins involved in post-translational interactions with type I collagen. Recently, a novel form of moderately severe OI caused by null mutations in TMEM38B was identified. TMEM38B encodes the ER membrane monovalent cation channel, TRIC-B, proposed to counterbalance IP3R-mediated Ca2+ release from intracellular stores.

Targeted re-sequencing of linkage region on 2q21 identifies a novel functional variant for hip and knee osteoarthritis.

Objective: The aim of the study was to identify genetic variants predisposing to primary hip and knee osteoarthritis (OA) in a sample of Finnish families.

Methods: Genome wide analysis was performed using 15 independent families (279 individuals) originating from Central Finland identified as having multiple individuals with primary hip and/or knee OA. Targeted re-sequencing was performed for three samples from one 33-member, four-generation family contributing most significantly to the LOD score.

The collagenopathies: review of clinical phenotypes and molecular correlations.

Genetic defects of collagen formation (the collagenopathies) affect almost every organ system and tissue in the body. They can be grouped by clinical phenotype, which usually correlates with the tissue distribution of the affected collagen subtype. Many of these conditions present in childhood; however, milder phenotypes presenting in adulthood are increasingly recognized.