Page 185 - MemoriaER-Eng

www.ciberer.es

• caParrós-Martín Ja, Valencia M, reytor e, Pacheco M, Fernández M, Perez-aytes a, Gean Most relevant
e, laPunzina P, Peters h, GoodshiP Ja, ruiz-Perez Vl. The ciliary Evc/Evc2 complex
scientific
interacts with Smo and controls Hedgehog pathway activity in chondrocytes by re-
gulating Sufu/Gli3 dissociation and Gli3 trafficking in primary cilia. Human Molecular
articles

Genetics (2013). 22(1):124-139.

• caParrós-Martín Ja, Valencia M, Pulido V, Martínez-Glez V, rueda-arenas i, aMr k, Fa-
c, l P, r-P Vl*, t s*, a M*.*=Corresponding authors.
rra aPunzinauizerezeMtaMyGlan
Clinical and molecular analysis in families with autosomal recessive osteogenesis
imperfecta identifies mutations in five genes and suggests genotype-phenotype co-

rrelations. Am J Med Genet A (2013). 61A:1354-69.

• keuPP k, beleGGia F, kayserili h, barnes aM, steiner M, seMler o, Fischer b, yiGit G, Janda

cy, becker J, breer s, altunoGlu u, GrünhaGen J, kraWitz P, hecht J, schinke t, MakareeVa
e, lausch e, cankaya t, caParrós-Martín Ja, laPunzina P, teMtaMy s, aGlan M, zabel b, eysel

P, koerber F, leikin s, García kc, netzer c, schönau e, ruiz-Perez Vl, Mundlos s, aMlinG
M, k u, M J, W b. Mutations in WNT1 cause different forms of bone
ornakariniollnik
fragility. American Journal of Human Genetics (2013). 92(4):565-74.

• Mitsushiro nakatoMi, Maria hoVorakoVa, aMel Gritli-linde, helen blair, kathleen Mcarthur,
M P, h l, r P, V l r-P, J G,
iroslaVeterkaerVéesotenataeterkoVaictoruizerezudithoodshiP
heiko Peters. Evc regulates a symmetric response to Shh signaling in molar develop-
ment. Journal of Dental Research (2013). 92(3):222-8.
´ó

During 2013 we have improved our current knowledge on the biology and func- Highlights
tion of Evc and Evc2, the two proteins mutated in Ellis-van Creveld syndrome

(EvC) and Weyers acrodental dysostosis (Weyers), and have demonstrated the
molecular mechanisms that differentiate the dominant from the recessive muta-

tions in EVC and EVC2 (Caparros-Martin et al. Hum Mol Genet 2013). We have

described: i) that Evc and Evc2 form a mutually protective protein complex, that
is both proteins are mutually required for maintaining their expression levels and

cellular localization at the base of primary cilia; ii) that Evc/Evc2 interact with

Smoothened, the main activator of Hedgehog (Hh) signalling, to mediate Gli3/
Sufu dissociation and Gli3 trafficking to the end of cilia, hence promoting target

gene transcription; and iii) that the dominant Evc2 variants associated with Wey-
ers patients form stable Evc/Evc2 complexes that instead of being localized at the

base of cilia are distributed along the entire organelle, indicating that localization

of Evc/Evc2 at the base of cilia is critical for Hh signalling. In contrast, the large
majority of Evc2 recessive variants present in EvC patients lead to non-stable

Evc/Evc2 complexes.

On the other hand, in 2013 we have collaborated with international groups in the

identification of WNT1 as a new gene mutated in osteogenesis imperfecta (OI)
) (Keupp et al., Am J Hum Genet 2013) and through the analysis of a cohort of 13
20
patients with OI we have described genotype-phenotype correlations useful in T
the clinic (Caparrs-Martin et al., Am J Med Genet A 2013). Finally, along with the OR
P
U753, we have conducted molecular diagnosis in EvC and OI patients and have RE
L
developed a NGS-based diagnostic tool to be used in the molecular diagnosis of A
these two diseases.
NU
N
A
R /
E
ER
B
CI

185