Bruck syndrome type 2 (Bruck syndrome 2) - Gen PLOD2.
Syndrome type 2 Bruck (BRKS2) is an autosomal recessive disease characterized by generalized osteopenia, congenital joint contractures, brittle bones, fractures with onset in early childhood, short stature, deformity member states, progressive scoliosis, and pterygium. Some people have affected bilateral inguinal hernias. This disease is distinguished from osteogenesis imperfecta by the absence of hearing loss and dentinogenesis imperfecta, and the presence of clubfoot and congenital joint limitations.
Syndrome type 2 Bruck is due to mutations in the PLOD2 gene, located on the long arm of chromosome 3 (3q24). This gene encodes a homodimeric membrane bound enzyme that is localized in the rough endoplasmic reticulum cisternae. The enzyme catalyzes the hydroxylation of lysine residues in collagen - like peptides. The resulting hydroxylysyl groups are binding sites for carbohydrates in collagen and therefore are critical for the stability of intermolecular crosslinks.
Mutations in the gene PLOD2 cause of Bruck syndrome type 2, results in a wide variety of phenotypes with varying degrees of severity of bone fragility and joint contractures. They have been identified homozygous missense mutations in exon 17 of the gene PLOD2. Another mutation in exon 17 of the PLOD2 gene, results in a substitution arg598. We have identified a homozygous mutation consisting of a duplication of a single nucleotide in the alternative 13th exon of the gene (1559dupC), indicating that the specific inactivation of protein isoform is enough to cause type 2 Bruck syndrome.
This disease is inherited in an autosomal recessive pattern, that is, both copies of the gene in every cell must have mutations for alteration is expressed. The parents of an individual with an autosomal recessive disease have a copy of the mutated gene, but usually show no signs and symptoms of the disease.
Tests performed in IVAMI: in IVAMI perform detection of mutations associated with syndrome type 2 Bruck, by complete PCR amplification of the exons of PLOD2 gene, and subsequent sequencing.
Samples recommended: EDTA blood collected for separation of blood leukocytes, or impregnated sample card with dried blood (IVAMI may mail the card to deposit the blood sample).