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=Cranio-lenticulo-sutural dysplasia=

Overview
Cranio-lenticulo-sutural dysplasia (CLSD, or Boyadjiev-Jabs syndrome) is caused by a disorder in the 14q13-q21 chromosome. It is an autosomal recessive disorder, meaning that both recessive genes must be carried in order for the disease to manifest itself. The disease causes a significant dilation of the endoplasmic reticulum of fibroblasts in the host with CLSD. Due to the distension of the endoplasmic reticulum, the export of proteins from the cell is disrupted as well as collagen secretion. This is usually the function of SEC23A in the genetic material, but, due to a missense mutation in this section, the cell is not able to support the normal exportation of proteins. It has also been hypothesized that there are other defects in the genetic code besides SEC23A that contribute to the disease.

Discovery
Cranio-lenticulo-sutural dysplasia was first discovered by Simeon Boyadjiev Boyd, chief of the Section of Genetics at UC Davis Children’s Hospital in 2003. CLSD was found in a consanguineous Saudi Arabian family. The children who were affected inherited the defective gene from both of their parents. Originally discovered in 5 males and 1 female from a large consanguineous Saudi Arabian family of Beduin decent (Boyadjiev, 1193).

Symptoms

 * Abnormal hair
 * Calvarial hypomineralization
 * Y-shaped cataracts by 1-2 years of age
 * Skeletal defects
 * Hypertelorism and other facial dysmorphisms
 * Facial dysmorphisms
 * Late-closing fontanels (soft spots in infants/kids)
 * Abnormal accumulation of proteins in the endoplasmic reticulum
 * scoliosis

Onset of the disease is in neonatal development and infancy.

Mutation
Mutation localized in the 14q13{q21 region of the chromosome 14 SEC23A gene This gene inactivates the SEC23A protein, which closes off the COP-II pathway, which is vital in the transportation of proteins from one part of the cell to the other. The inability for proteins to travel enlarges the endoplasmic reticulum, and therefore alters the normal growth patterns of skeletal and muscle tissues. This is evidenced by a low concentration extracellular collagen in affected cells. The same affected cells contain a much larger intercellular concentration of collagen than normal cells. Collagen aids in the ossification process of bone formation. Thus, diseased cells are unable to transport collagen effectively and bone mineralization is hindered. Probability that the defect is found in the ability to form a working complex with SEC13-SEC31 (pg 1195)

Frequency
Estimated to affect one in every 500 to 1,000 babies in the United States of America Recommended that CLSD is evaluated in all patients with late-closing fontanels and hypertelorism Genetic Testing?

Current Research
Zebrafish were used as a model organism to take advantage of their transparent embryos. Zebrafish were implanted with the abnormal gene. Observations include:
 * expression in developing head cartilages
 * expression in all main neurocrainial and vicerocranial cartilages of the head
 * scapulocoracoid and postcoracoid processes of the pectoral fin and distal edge of endoskeletal disc

Prognosis
Good, and treatment is symptomatic. As of the most recent published articles, identified children were still alive at over 4 years of age. Mutant proteins still maintain some residual activity (pg 1195)