The molecular genetic classification

of OI has shown to be very heterogeneous, with different patterns of inheritance and wide variability of clinical severity.10 Glorieux et al.11 described an autosomal dominant form of OI, similar to OI Sillence type IV, but with distinct clinical, histological, and molecular characteristics. No mutations were found in COL1A1 and COL1A2 and, therefore, it was called OI type V (OMIM #610967) by the authors. Approximately 65% of affected individuals develop hyperplastic callus after fractures or surgical interventions, considered a pathognomonic characteristic. 12 ABT-199 purchase Only in 2012 were IFITM5 mutations identified in patients with type V OI, the gene encoding interferon-induced transmembrane protein 5, by sequencing of the entire exome. 12, 13 and 14

The encoded protein has a role in early mineralization, but its mechanism remains unknown. 10 In 2006, a CRTAP gene mutation was identified as the first genetic cause of lethal recessive OI. 15 Since then, new mutations in genes that cause recessive OI have been identified by exome sequencing, such as FKBP10, LEPRE1, PLOD2, PPIB, SERPINF1, SERPINH1, SP, BMP1, and TMEM38B. Each of these genes received an OI type number in the OMIM database, following the sequence numbers of the Sillence classification. OI type VI AZD0530 cell line (OMIM #613982) is an autosomal recessive form of the disease that can be caused by a homozygous mutation in the gene SERPINF1 in chromosome 17p13.3, causing a mineralization defect. Idoxuridine 14 According to the classification of Sillence et al., the phenotype is compatible with type IV or type III. 16 and 17 OI type VII (MIM #610682) is a lethal autosomal recessive form of OI, caused by a mutation in CRTAP gene in homozygosity or compound heterozygosity in chromosome 3p22. It accounts for 2% to 3% of cases of

lethal OI. 15 Cabral et al.18 described a form of autosomal recessive OI, called OI type VIII (OMIM #610915), which is characterized by white sclera, severe growth impairment, very poor skeletal mineralization, and bulbous metaphyses. This form is caused by mutations in the gene encoding leprecan (LEPRE1) in chromosome 1p34.2, associated with severe or lethal OI. OI type IX (OMIM #259440) is an autosomal recessive form of OI corresponding to clinically severe types II/III of the Sillence classification.19 There are no reports of dentinogenesis imperfecta. It can be caused by a homozygous mutation in the PPIB gene in chromosome 15q22.31. OI type X (OMIM #613848) is an autosomal recessive form of the disease that can be caused by a homozygous mutation in the gene SERPINH1 in chromosome 11q13.5. It is characterized by bone deformities and multiple fractures, generalized osteopenia, dentinogenesis imperfecta, and blue sclera.