Osteogenesis Imperfecta, Type Xiv

A number sign (#) is used with this entry because autosomal recessive osteogenesis imperfecta type XIV (OI14) can be caused by homozygous mutation in the TMEM38B gene (611236) on chromosome 9q31.

Description

Osteogenesis imperfecta (OI) is a connective tissue disorder characterized by bone fragility and low bone mass. Due to considerable phenotypic variability, Sillence et al. (1979) developed a classification of OI subtypes based on clinical features and disease severity: OI type I, with blue sclerae (166200); perinatal lethal OI type II, also known as congenital OI (166210); OI type III, a progressively deforming form with normal sclerae (259420); and OI type IV, with normal sclerae (166220). Most cases of OI are autosomal dominant with mutations in 1 of the 2 genes that code for type I collagen alpha chains, COL1A1 (120150) and COL1A2 (120160).

Shaheen et al. (2012) described osteogenesis imperfecta type XIV (OI14), an autosomal recessive form of the disorder characterized by variable degrees of severity of multiple fractures and osteopenia, with normal teeth, sclerae, and hearing. Fractures first occur prenatally or by age 6 years.

Clinical Features

Shaheen et al. (2012) described 3 consanguineous Saudi families with a history of fractures. The patients who were studied from these families ranged in age from 2.8 to 16 years. Occurrence of first fracture ranged from prenatal onset to 6 years of age. Most had variable degrees of severity of multiple fractures and osteopenia. None had blue sclerae, abnormal teeth, progressive hearing loss, or other organ involvement.

Mapping

By autozygosity and linkage mapping in 3 multiplex consanguineous Saudi families with OI, Shaheen et al. (2012) found linkage of the disorder to chromosome 9q31.1-q31.3.

Molecular Genetics

Shaheen et al. (2012) described 2 simplex and 11 multiplex families encompassing 27 patients with OI. By exome sequencing and haplotype analysis within a critical interval on chromosome 9 identified in 3 of the consanguineous Saudi families, Shaheen et al. (2012) identified a homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members (611236.0001). In 6 other families, homozygous mutations were found in the previously described OI genes SERPINF1 (172860), CRTAP (605497), and LEPRE1 (610339). Gonadal or gonadal/somatic mosaic mutations in the COL1A1 or COL1A2 genes were identified in the remaining families.

Volodarsky et al. (2013) identified the same homozygous truncating deletion of exon 4 of the TMEM38B gene in affected members of 3 unrelated Israeli Bedouin consanguineous families segregating OI.