Spondyloperipheral dysplasia
Encyclopedia
Spondyloperipheral dysplasia is an autosomal
dominant disorder of bone
growth. The condition is characterized by flattened bones of the spine
(platyspondyly) and unusually short fingers and toes (brachydactyly
). Some affected individuals also have other skeletal abnormalities, short stature, nearsightedness (myopia
), hearing loss, and mental retardation
. Spondyloperipheral dysplasia is a subtype of collagenopathy, types II and XI
.
Spondyloperipheral dysplasia is one of a spectrum of skeletal disorders caused by mutations in the COL2A1 gene
, located on chromosome
12q13.11-q13.2
. The protein made by this gene forms type II collagen
, a molecule found mostly in cartilage
and in the clear gel that fills the vitreous humour
(the eyeball). Type II collagen is essential for the normal development of bones and other connective tissues (the tissues that form the body's supportive framework).
Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules. The protein made by the altered COL2A1 gene cannot be used to make type II collagen, resulting in a reduced amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones, leading to the signs and symptoms of spondyloperipheral dysplasia.
The disorder is believed to be inherited in an autosomal dominant manner. This indicates that the defective gene responsible for the disorder is located on an autosome
(chromosome 12 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
dominant disorder of bone
Bone
Bones are rigid organs that constitute part of the endoskeleton of vertebrates. They support, and protect the various organs of the body, produce red and white blood cells and store minerals. Bone tissue is a type of dense connective tissue...
growth. The condition is characterized by flattened bones of the spine
Vertebral column
In human anatomy, the vertebral column is a column usually consisting of 24 articulating vertebrae, and 9 fused vertebrae in the sacrum and the coccyx. It is situated in the dorsal aspect of the torso, separated by intervertebral discs...
(platyspondyly) and unusually short fingers and toes (brachydactyly
Brachydactyly
Brachydactyly , is a medical term which literally means "shortness of the fingers and toes" . The shortness is relative to the length of other long bones and other parts of the body. Brachydactyly is an inherited, usually dominant trait...
). Some affected individuals also have other skeletal abnormalities, short stature, nearsightedness (myopia
Myopia
Myopia , "shortsightedness" ) is a refractive defect of the eye in which collimated light produces image focus in front of the retina under conditions of accommodation. In simpler terms, myopia is a condition of the eye where the light that comes in does not directly focus on the retina but in...
), hearing loss, and mental retardation
Mental retardation
Mental retardation is a generalized disorder appearing before adulthood, characterized by significantly impaired cognitive functioning and deficits in two or more adaptive behaviors...
. Spondyloperipheral dysplasia is a subtype of collagenopathy, types II and XI
Collagenopathy, types II and XI
The type II and XI collagenopathies are a group of disorders that affect connective tissue, the tissue that supports the body's joints and organs. These disorders are caused by defects in type II or type XI collagen. Collagens are complex molecules that provide structure, strength, and elasticity ...
.
Cause and Genetics
Gene
A gene is a molecular unit of heredity of a living organism. It is a name given to some stretches of DNA and RNA that code for a type of protein or for an RNA chain that has a function in the organism. Living beings depend on genes, as they specify all proteins and functional RNA chains...
, located on chromosome
Chromosome
A chromosome is an organized structure of DNA and protein found in cells. It is a single piece of coiled DNA containing many genes, regulatory elements and other nucleotide sequences. Chromosomes also contain DNA-bound proteins, which serve to package the DNA and control its functions.Chromosomes...
12q13.11-q13.2
Chromosome 12 (human)
Chromosome 12 is one of the 23 pairs of chromosomes in humans. People normally have two copies of this chromosome. Chromosome 12 spans about 143 million base pairs and represents between 4 and 4.5 percent of the total DNA in cells.Identifying genes on each chromosome is an active area of genetic...
. The protein made by this gene forms type II collagen
Collagen
Collagen is a group of naturally occurring proteins found in animals, especially in the flesh and connective tissues of mammals. It is the main component of connective tissue, and is the most abundant protein in mammals, making up about 25% to 35% of the whole-body protein content...
, a molecule found mostly in cartilage
Cartilage
Cartilage is a flexible connective tissue found in many areas in the bodies of humans and other animals, including the joints between bones, the rib cage, the ear, the nose, the elbow, the knee, the ankle, the bronchial tubes and the intervertebral discs...
and in the clear gel that fills the vitreous humour
Vitreous humour
The vitreous humour or vitreous humor is the clear gel that fills the space between the lens and the retina of the eyeball of humans and other vertebrates...
(the eyeball). Type II collagen is essential for the normal development of bones and other connective tissues (the tissues that form the body's supportive framework).
Mutations in the COL2A1 gene interfere with the assembly of type II collagen molecules. The protein made by the altered COL2A1 gene cannot be used to make type II collagen, resulting in a reduced amount of this type of collagen in the body. Instead of forming collagen molecules, the abnormal protein builds up in cartilage cells (chondrocytes). These changes disrupt the normal development of bones, leading to the signs and symptoms of spondyloperipheral dysplasia.
The disorder is believed to be inherited in an autosomal dominant manner. This indicates that the defective gene responsible for the disorder is located on an autosome
Autosome
An autosome is a chromosome that is not a sex chromosome, or allosome; that is to say, there is an equal number of copies of the chromosome in males and females. For example, in humans, there are 22 pairs of autosomes. In addition to autosomes, there are sex chromosomes, to be specific: X and Y...
(chromosome 12 is an autosome), and only one copy of the defective gene is sufficient to cause the disorder, when inherited from a parent who has the disorder.