Kniest dysplasia (Kniest dysplasia) - Gen COL2A1
Kniest dysplasia is collagenopathy collagen II affecting bone growth and is characterized by short stature (dwarfism), other skeletal abnormalities and hearing and vision problems. The latter are mostly myopia, vitreous degeneration and retinal detachment. Skeletal features may include kyphoscoliosis, platyspondyly, dumbbell - shaped bones in the arms and legs, long, gnarled fingers, and clubfoot. Skeletal abnormalities may limit physical activity if they cause movement restrictions. In addition, joint problems may also cause arthritis.
The abnormalities associated with Kniest dysplasia result from mutations in the COL2A1 gene, located on the long arm of chromosome 12 (12q13.11). This gene encodes a component of collagen type II, called the pro-alpha1 (II) chain. This type of collagen is found primarily in the vitreous and cartilage. Collagen type II is essential for normal bone development and other connective tissues that form the support frame body. Collagen type II is also part of the vitreous, the inner ear, and the nucleus pulposus.
They described more than 20 mutations in the COL2A1 gene in people with dysplasia Kniest. Most of these mutations eliminate one or more nucleotides in the COL2A1 gene. These genetic changes lead to abnormally short encoding pro-alpha1 (II) chains, which then bind to the normal length chains. This type II collagen abnormal prevents bone and other connective tissues develop properly, which results in the characteristics of the Kniest dysplasia.
A wide phenotypic variability due to genetic alterations in the COL2A1 gene ranging from lethal dwarfism at birth, in cases of type 2 Achondrogenesis or some case Spondyloepiphyseal dysplasia congenita, to minimal skeletal abnormalities, and Stickler syndrome I . Kniest dysplasia, moderately severe, is in the midst of the phenotypic spectrum of these collagenopathies. The type of mutation and the particular location in the COL2A1 sequence which will determine the severity of collagenosis, hence the importance of molecular diagnostics. In general, the more severe phenotypes associated with mutations that cause protein truncation or severely abnormal collagen generate while milder phenotypes are usually generated by point mutations that result in a decrease in collagen production. Most mutations associated Kniest dysplasia are small deletions are located between exons 12 and 24 of the COL2A1 gene.
Kniest dysplasia is inherited as an autosomal dominant, which means that a copy of the altered gene in each cell is sufficient to express the disease.
Tests in IVAMI: in IVAMI perform detection of mutations associated with Kniest dysplasia, by complete PCR amplification of exons COL2A1 gene, and subsequent sequencing. Because most mutations associated Kniest dysplasia have been located between exons 12 and 24 of the COL2A1 gene, it is recommended to start the study for them can, in any case, complete the study of the entire gene, if if desired.
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) if postnatal diagnosis. For prenatal diagnosis, amniotic fluid or chorionic villi.