Table 1. Finally identified variants in CMI families.

Gene	Gene functiona	Variant	SIFTb	Polyphen-2c	Mutation Tasterd	Expressione	Animal models
Family #VED
FBN3	Extracellular matrix constituent	c.143G>A:p.(R48Q)	D	PD	P	Connective tissue	—
ITGA10	Glycoprotein involved in cell adhesion	c.1681C>G:p.(Q561E)	T	B	DC	Lung, heart, chondrocytes	Mild chondrodysplasiaf
EP300	Transcriptional co-activator	c.7168G>A:p.(A2390T)	T	PD	DC	Bone marrow	—
DKK1	Inhibitor of the WNT pathway	c.121G>A:p.(A41T)	D	PD	DC	Chondrocytes, osteocytes	Lethal, absence of the head, digits anomaliesg
MATN3	Cartilage matrix component	c.526G>T:p.(V176L)	T	B	P	Primitive streak, chondrocytes	Abnormalities of the knee and joint cartilagesh
Family #DRN
LRP4	Inhibitor of the WNT pathway	c.2552C>G:p.(T851R)	D	B	D	Osteoblasts, osteocytes	Bone and cranium anomaliesi
EXT2	Glycosyltransferases involved in the synthesis of heparan sulfate	c.1178G>A: p.(R393K)	T	B	D	Ubiquitous	Ectopic bone growthj
BMP1	Peptidase capable to induce cartilage formation	c.941G>A:p.(R314H)	D	D	D	Ubiquitous	Lethal, failure of the closure of body wallk

Abbreviations: B, benign; D, damaging; DC, disease causing; PD, probably damaging; T, tolerated.

The DNA mutation and amino-acid numbering systems are based on the following cDNA sequences accession numbers: FBN3 NM_032447; ITGA10 NM_003637; EP300 NM_001429; DKK1 NM_012242; MATN3 NM_002381; LRP4 NM_002334, EXT2 NM_000401; BMP1 NM_001199 and protein sequences accession numbers: DKK1 NP_036374: FBN3 NP_115823; ITGA10 NP_003628; EP300 NP_001420; MATN3 NP_002372; LRP4 NP_002325 EXT2 NP997005; BMP1 NP_001190.

^aAccording to GeneCards Database (http://www.genercards.org).

^bSIFT, the Sorting Intolerant from Tolerant algorithm (http://www.jcvi.org/).

^cPolyphen-2, polymorphism phenotyping 2 (http://genetics.bwh.harvard.edu/).

^dhttp://www.mutationtaster.org.

^eAccording to GeneCards Database.

^fBengtsson et al.⁴⁵

^gMukhopadhyay et al.²⁴

^hYang et al.⁴⁶

ⁱJohnson et al.²⁹

^jStickens et al.⁴⁷

^kSuzuki et al.³³