Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XI is an autosomal recessive form of OI (summary by Alanay ... Osteogenesis imperfecta (OI) comprises a group of connective tissue disorders characterized by bone fragility and low bone mass. The disorder is clinically and genetically heterogeneous. OI type XI is an autosomal recessive form of OI (summary by Alanay et al., 2010).
Alanay et al. (2010) studied 5 consanguineous families from northern Turkey in which a severe progressive deforming type of OI cosegregated with autosomal recessive epidermolysis bullosa simplex (131900), the latter resulting from a defect in keratin-14 (148066). Dentinogenesis ... Alanay et al. (2010) studied 5 consanguineous families from northern Turkey in which a severe progressive deforming type of OI cosegregated with autosomal recessive epidermolysis bullosa simplex (131900), the latter resulting from a defect in keratin-14 (148066). Dentinogenesis imperfecta, a feature of OI type III (259420), was absent. The histologic features included a distorted lamellar structure and a fish scale-like pattern, along with elevated serum alkaline phosphatase. Alanay et al. (2010) also studied a Mexican family in which 3 sibs of consanguineous parents had severe progressive deforming OI. Steinlein et al. (2011) described 3 German male sibs with a severe form of OI who were homozygous for a mutation in the FKBP10 gene (607063.0008). All 3 had dentinogenesis imperfecta and none showed contractures or webbing.
In affected members of 5 consanguineous Turkish families segregating autosomal recessive epidermolysis bullosa simplex (139100) and OI type XI, Alanay et al. (2010) identified homozygosity for 2 mutations: a missense mutation in the KRT14 gene (148066.0006) known to ... In affected members of 5 consanguineous Turkish families segregating autosomal recessive epidermolysis bullosa simplex (139100) and OI type XI, Alanay et al. (2010) identified homozygosity for 2 mutations: a missense mutation in the KRT14 gene (148066.0006) known to cause EB simplex and an in-frame deletion in the FKBP10 gene (607063.0001) causing OI. In 3 Mexican sibs with OI type XI, they identified homozygosity for a null mutation in the FKBP10 gene (607063.0002). Neither mutation was found in a panel of 210 alleles from ethnically matched unaffected individuals. The FKBP10 gene encodes a chaperone that participates in type I procollagen folding, and Alanay et al. (2010) determined that FKBP10 mutations affect type I procollagen secretion. In 2 brothers with Bruck syndrome (BRKS1; 259450), Shaheen et al. (2010) identified a homozygous mutation in the FKBP10 gene (607063.0003). They suggested that their patients and the patients reported by Alanay et al. (2010) with OI may both have had Bruck syndrome and that bisphosphonate therapy may explain the less severe phenotype in their patients. In response to Shaheen et al. (2010), Alanay and Krakow (2010) noted that a wide phenotypic range of severity can result from different mutations in the same gene and suggested that the disorder caused by mutation in the FKBP10 gene be categorized as a recessive form of progressive deforming OI with or without joint contractures. Kelley et al. (2011) sequenced the FKBP10 gene in 6 individuals from 5 families with a moderately severe OI phenotype, 4 with congenital joint contractures (Bruck syndrome; 259450) and 1 (patient 2) without contractures. The patient without contractures had a 35-bp deletion (607063.0004). Barnes et al. (2012) identified a Palestinian pedigree with moderate and lethal forms of recessive OI caused by mutations in the FKBP10 or PPIB (123841) gene. In 1 pedigree branch, a child with moderate type XI OI was homozygous for the indel mutation in the FKBP10 gene (607063.0009) previously identified in a Bruck syndrome patient. In the other pedigree branch, both parents carried a deletion in the PPIB gene (123841.0004) causing lethal OI type IX (OI9; 259440) in their 2 children.