| Family / report | Mutation (DNA level) | Mutation (protein level) | Mutation type | Exon / intron location | Effect on CyPB protein | Clinical severity | Reference / year |
|---|---|---|---|---|---|---|---|
| van Dijk family 1 | c.556_559delAAGA | p.Lys186Glnfs*8 | Homozygous frameshift deletion | Exon 5 | Replaces the last 31 highly conserved C-terminal amino acids; mutant mRNA present, but intracellular CyPB was undetectable in proband fibroblasts, consistent with absent or unstable truncated protein (pqac-00000008, pqac-00000009) | Perinatal lethal / severe, compatible with Sillence type II-B; prenatal fractures, bowed/fractured long bones without rhizomelia (pqac-00000008, pqac-00000014) | van Dijk et al., 2009 (pqac-00000007, pqac-00000008, pqac-00000009) |
| van Dijk family 2 | c.451C>T | p.Gln151* | Homozygous nonsense | Exon 4 | Premature truncation removing the last 65 amino acids at the C-terminus; predicted to impair function or trigger nonsense-mediated decay (pqac-00000009) | Severe deforming to moderately severe OI; one child survived with OI type III, marked short stature, kyphoscoliosis, wheelchair dependence; affected sib diagnosed prenatally/neonatally (pqac-00000008) | van Dijk et al., 2009 (pqac-00000007, pqac-00000008, pqac-00000009) |
| Pyott family 1 (P1) | c.414_423del | p.Ser139Thrfs*21 | Homozygous frameshift deletion | Exon 4 | Creates a premature termination codon 61 nt downstream; marked nonsense-mediated mRNA decay; predicted shortened 158-aa protein not detected on western blot (pqac-00000015, pqac-00000016) | Perinatal lethal to very severe OI phenotype (study cohort range stated as perinatal lethal to moderate) (pqac-00000003, pqac-00000036) | Pyott et al., 2011 (pqac-00000015, pqac-00000016, pqac-00000036) |
| Pyott family 2 (P2) | c.120delC + c.313G>A | frameshift allele truncating downstream of c.120delC; p.Gly105Arg on second allele | Compound heterozygous: frameshift + missense | Exon 2 + exon 2 | c.120delC allele undergoes rapid mRNA degradation; only the c.313A transcript is readily detected in cDNA; western blot showed only a very small amount of CYPB protein, indicating marked reduction of residual protein (pqac-00000011) | Moderate OI within reported spectrum; study title and text state phenotypes ranged from perinatal lethal to moderate (pqac-00000003, pqac-00000036) | Pyott et al., 2011 (pqac-00000011, pqac-00000036) |
| Pyott family 3 (P3) | c.343+1G>A | Splice defect causing p.Gly115 deletion plus 10-aa insertion in one transcript; exon 3 skipping in alternate transcript | Homozygous splice-donor mutation | Intron 3 donor site | Produced two abnormal transcripts: one with retention of 27 bp of intron 3 yielding an in-frame altered protein, and one with exon 3 skipping causing frameshift/PTC and NMD; no CYPB detected on western blot (pqac-00000010, pqac-00000011) | Moderate OI within reported spectrum; radiographs at 9–16 years showed broad poorly modeled femora, cortical thinning, and stable scoliosis (pqac-00000012, pqac-00000036) | Pyott et al., 2011 (pqac-00000010, pqac-00000011, pqac-00000012, pqac-00000036) |
| Additional patients noted in later review | Start-codon Arg-to-Met substitution (exact cDNA not provided in available context) | Arg-to-Met substitution affecting translation initiation / start codon | Start-codon missense / initiation codon defect | Start codon | Reported in other OI type IX patients; notable because it was described as not delaying collagen folding or altering proline 3-hydroxylation levels in the cited review summary, suggesting residual or atypical function (pqac-00000017) | OI type IX with severe bone deformities in broader phenotype spectrum; exact family-level severity not detailed in available context (pqac-00000017, pqac-00000023) | Cotti et al., 2025 review summary (pqac-00000017, pqac-00000023) |


*Table: This table summarizes the reported PPIB variants associated with osteogenesis imperfecta type IX, including their molecular class, predicted effect on cyclophilin B, and associated clinical severity. It is useful for linking genotype to mechanism and phenotype across the key early case series and later review evidence.*