Homozygosity for a missense mutation in SERPINH1, which encodes the collagen chaperone protein HSP47, results in severe recessive osteogenesis imperfecta.

[dentinogenesis imperfecta]

Osteogenesis imperfecta (OI ) is characterized by bone fragility and fractures that may be accompanied by bone deformity , dentinogenesis imperfecta , short stature , and shortened life span . About 90 % of individuals with OI have dominant mutations in the type I collagen genes COL 1 A 1 and COL 1 A 2 . Recessive forms of OI resulting from mutations in collagen-modifying enzymes and chaperones CRTAP , LEPRE 1 , PPIB , and FKBP 10 have recently been identified . We have identified an autosomal-recessive missense mutation (c .233 T >C , p .Leu 78 Pro ) in SERPINH 1 , which encodes the collagen chaperone-like protein HSP 47 , that leads to a severe OI phenotype . The mutation results in degradation of the endoplasmic reticulum resident HSP 47 via the proteasome . Type I procollagen accumulates in the Golgi of fibroblasts from the affected individual and a population of the secreted type I procollagen is protease sensitive . These findings suggest that HSP 47 monitors the integrity of the triple helix of type I procollagen at the ER /cis-Golgi boundary and , when absent , the rate of transit from the ER to the Golgi is increased and helical structure is compromised . The normal 3 -hydroxylation of the prolyl residue at position 986 of the triple helical domain of proalpha 1 (I ) chains places the role of HSP 47 downstream from the CRTAP /P 3 H 1 /CyPB complex that is involved in prolyl 3 -hydroxylation . Identification of this mutation in SERPINH 1 gives further insight into critical steps of the collagen biosynthetic pathway and the molecular pathogenesis of OI .

Diseases
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Diseases presenting "mutations in the type i collagen genes col1a1" symptom

dentinogenesis imperfecta

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