Osteogenesis Imperfecta Genotypes and Genotype–Phenotype Relationships

Dalgleish, Raymond

doi:10.1016/b978-0-12-397165-4.00010-1

Cited by 4 publications

(8 citation statements)

References 68 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Severity of OI mutation is determined by a number of genetic factors, including location, mutation type and mutated residues. Over 1,000 different COL1A1 / COL1A2 mutations have been identified in patients with OI ( 11 ), accounting for ~90% of OI cases in patients with OI type I–IV. Additionally, there are a number of mutations identified in genes encoding proteins that interact with type I collagen, affecting the development of bones and leading to different symptoms of OI.…”

Section: Discussionmentioning

confidence: 99%

“…PCR products were stained with ethidium bromide and visualized on a UV transilluminator following 1.5% agarose gel electrophoresis and were sequenced directly in an ABI 3130 genetic analyzer (Thermo Fisher Scientific, Inc.). When a potential novel mutation was considered following alignment of the patient's genome sequence against the ClinVar ( ), HGMD ( ), HPSD (liweilab.genetics.ac.cn/HPSD/), the SNP ( ) databases and osteogenesis imperfecta and Ehlers-Danlos syndrome variant databases ( 11 ), direct sequencing of the amplified PCR products from the same region of the 300 unaffected patients was performed to verify the possibility of the difference being caused by a polymorphism. Sorting Intolerant From Intolerant ( 12 ), PolyPhen 2.0 ( 13 ) and Mutation Taster ( 14 ) tools were used to evaluate the pathology of the novel mutations.…”

Section: Methodsmentioning

confidence: 99%

“… Adapted from the osteogenesis imperfecta and Ehlers-Danlos syndrome variant databases ( 11 ). OI, osteogenesis imperfecta; COL1A1, collagen α-1(I) chain.…”

Section: Figurementioning

confidence: 99%

“…COL1A1 and COL1A2 are ~18 kb and 38 kb long, respectively and are located in 17q21.3–17q22, 7q21.3–7q22.3, respectively, both with >50 exons. To date, >1,000 different COL1A1 / COL1A2 mutations have been identified in patients with OI ( 11 ). The present study reports a Chinese patient with OI type IV disease, who carried a novel missense mutation c.281T>A in the N-propeptide of collagen type I α chain in the COL1A1 gene.…”

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level caused by a Val94Asp mutation in COL1A1

Yang

Luo

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

Osteogenesis imperfecta (OI) is a rare congenital disorder characterized by bone fragility and fractures, and associated with bone deformity, short stature, dentin, ligament and blue-gray eye sclera. OI is caused by a heterozygous mutation in collagen α-1(I) chain (COL1A1) or collagen α-2(I) chain (COL1A2) genes that encode α chains of type I collagen. Collagen α chain peptide contains an N-propeptide, which has a role in assembly and processing of collagen. Point mutations in the N-propeptide domain appear to trigger OI. In the present study, a novel heterozygous missense mutation, c.281T>A (p.Val94Asp), was identified in the von Willebrand C domain of N-terminal of type I collagen in an individual with type IV OI. The majority of N-terminal mutations are associated with OI/Ehlers-Danlos syndrome (EDS); however, in the present study, the affected individual did not suffer from EDS and the level of serum phosphorus of the patient was low (0.67 mmol/l). A number of clinical phenotypes were observed at the same variation site or in the same region on the polypeptide chain of COL1A, which suggests that additional genetic and environmental factors may influence the severity of OI. The present study may provide insight into the phenotype-genotype association in collagen-associated diseases and improve clinical diagnosis of OI.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

“… Adapted from the osteogenesis imperfecta and Ehlers-Danlos syndrome variant databases ( 11 ). OI, osteogenesis imperfecta; COL1A1, collagen α-1(I) chain.…”

Section: Figurementioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

A novel variant of osteogenesis imperfecta type IV and low serum phosphorus level caused by a Val94Asp mutation in COL1A1

Yang

Luo

et al. 2018

Mol Med Report

View full text Add to dashboard Cite

show abstract

“…Potentially pathogenic mutations may occur in any of the 338 Gly‐Xaa‐Yaa triplets following the change of a single nucleotide in the codon for glycine (GGG, GGA, GGC, GGT). Depending on the location, the change can result in the glycine substitution for one of eight possible amino acids, i.e., alanine, arginine, aspartic acid, cysteine, glutamic acid, serine, tryptophan, or valine (Dalgleish, 2014 ). Previous studies on patients with OI have reported examples of seven such substitutions in the COL1A1 gene, involving all but the tryptophan residue, this being a large, non‐polar aromatic amino acid containing an indole side chain.…”

Section: Introductionmentioning

confidence: 99%

The first glycine‐to‐tryptophan substitution in the COL1A1 gene identified in a patient with progressively‐deforming Osteogenesis imperfecta

Sałacińska

Michałus

Pinkier

et al. 2022

Molec Gen & Gen Med

View full text Add to dashboard Cite

Background Osteogenesis imperfecta (OI) is a genetic disorder of connective tissue with variable phenotype and heterogeneous genetic background. Majority of reported mutations are glycine substitutions, whose clinical outcome ranges from mild to perinatal lethal. The phenotype appears to be influenced by the properties of amino acid side chain and the degree of structural aberration of collagen molecules. Since the genotype–phenotype correlation remains unclear, the severity of mutation is mostly predicted according to previously‐reported cases. Although the number of OI variants is constantly expanding, no glycine‐to‐tryptophan substitutions have been reported in COL1A1 gene. Methods A sample from a 15‐year‐old girl presenting with progressively‐deforming OI type III was tested using an NGS custom gene panel. Multiple bioinformatic and interpretation tools, including mutation databases and conservation analysis, were used for variant classification. The presence of the mutation was verified by Sanger sequencing. Results A novel heterozygous mutation c.733G>T was identified in the COL1A1 gene (p.Gly245Trp). Conclusions The discovery of this novel glycine‐to‐tryptophan substitution located in the COL1A1 gene broadens the spectrum of mutations underlying this rare disease and provides useful information on the clinical outcome of such substitutions.

show abstract