Mutations in Fibronectin Cause a Subtype of Spondylometaphyseal Dysplasia with "Corner Fractures".

Fibronectin is a master organizer of extracellular matrices (ECMs) and promotes the assembly of collagens, fibrillin-1, and other proteins. It is also known to play roles in skeletal tissues through its secretion by osteoblasts, chondrocytes, and mesenchymal cells. Spondylometaphyseal dysplasias (SMDs) comprise a diverse group of skeletal dysplasias and often manifest as short stature, growth-plate irregularities, and vertebral anomalies, such as scoliosis.

Phenotypic variability of osteogenesis imperfecta type V caused by an IFITM5 mutation.

In a large cohort of osteogenesis imperfecta type V (OI type V) patients (17 individuals from 12 families), we identified the same mutation in the 5' untranslated region (5'UTR) of the interferon-induced transmembrane protein 5 (IFITM5) gene by whole exome and Sanger sequencing (IFITM5 c.-14C > T) and provide a detailed description of their phenotype. This mutation leads to the creation of a novel start codon adding five residues to IFITM5 and was recently reported in several other OI type V families.

Disease gene characterization through large-scale co-expression analysis.

Background: In the post genome era, a major goal of biology is the identification of specific roles for individual genes. We report a new genomic tool for gene characterization, the UCLA Gene Expression Tool (UGET).

Results: Celsius, the largest co-normalized microarray dataset of Affymetrix based gene expression, was used to calculate the correlation between all possible gene pairs on all platforms, and generate stored indexes in a web searchable format.

Genetic determinants of osteoporosis susceptibility in a female Ashkenazi Jewish population.

Purpose: To determine the heritability of low bone mineral density (BMD) at the hip in Ashkenazi Jewish families.

Methods: BMD at hip was accessed by dual x-ray absorptiometry (DEXA) in 166 female subjects from 61 families. Variance component analysis was used to estimate genetic contributions.

The observed human sperm mutation frequency cannot explain the achondroplasia paternal age effect.

The lifelong spermatogonial stem cell divisions unique to male germ cell production are thought to contribute to a higher mutation frequency in males. The fact that certain de novo human genetic conditions (e.g.