Pathogenic mechanisms of osteogenesis imperfecta, evidence for classification

Table 1 Pathogenesis and genetic typing of OI

Typing	Pathogenic mechanism	Sub-type	Pre-existing typing	Pathogenic genes	Mutant proteins	Mode of inheritance	Phenotype lightness and weight
Type 1	Type I Collagen defects	1 A	Type I	COL1A1	α1 chain	AD	Mild
		1 A	Type II-IV	COL1A1, COL1A2	α2 chain	AD	More severe clinical phenotype or lethality
		1B	Type XIII	BMP1	BMP1	AR	More severe
		1B	Type VIIC	ADAMT-2	ADAMT-2	AR	ESD, not OI
		1 C	Type VII	CRTAP	CRTAP	AR	Severe to lethality
			Type VIII	LEPRE1	P3H1	AR	Severe to lethality
			Type IX	PPIB	CypB	AR	Extremely rare
			Type XIV	TMEMB38	TRIC-B	AR	Asymptomatic individual to severe OI
		1D	Type X	SERPINH1	HSP47	AR	Severe
			Type XI	FKBP10	FKBP65	AR
			-	KDELR2	KDELR2	AR
			-/BS	PLOD2	LH2	AR
Type 2	Bone mineralization defects		Type V	IFITM5	BRIL	AD	Usually a moderate OI, similar in severity to type IV OI
			Type VI	SERPINF1	PEDF	AR	Severe bone dysplasia
			Special Type VI	IFITM5	BRIL (Ser40Leu)	AD	More severe than typical Type VI OI
Type 3	Defective osteoblast differentiation and function		Type XVI	CREB3L1	OASIS	AR	Mild or lethality
			Type XVIII	MBTPS2	S2P	XR	Moderate severity
			Type XV	WNT1	WNT1	AR	Moderate to progressive deformation
			Type XII	SP7	Osterix	AR
			Type XVII	SPRAC	Osteonectin	AR
Type 4	Unclassified and untyped OI		-	FAM46A	FAM46A	AR
			-	MESD	MESD	AR	Can cause stillbirth, drugs that enhance Wnt signaling such as anti-sclerostin antibodies may have potential therapeutic efficacy
			-	CCDC134	CCDC134	AR

OI: osteogenesis imperfecta; BS: Bruck syndrome; EDS: Ehlers-Danlos syndrome; AD: autosomal dominant; AR: autosomal recessive; XR: X-linked recessive

ISSN: 1750-1172