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In addition to heterotopic bone formation, individuals with FOP also exhibit malformations of the normotopic skeleton.
Combinatorial Dlx mutants exhibit malformations of the distal limb (reviewed in [ 2]), but the limb itself still forms.
Patients with OAS exhibit malformations of the outer ear (pinna) and defects of the eye, including microphthalmia, cataract, coloboma and retinal dystrophy (Schorderet et al., 2008; Vaclavik et al., 2011).
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Zebrafish expressing the gridlock mutation grl in the hey2 gene exhibit malformation of the aorta (Weinstein et al., 1995).
In addition to malformed ears, dumbo mice exhibit eye malformations, although less severe than those observed in the OAS patients identified to date.
Aldh1a2−/− embryos die around embryonic day (E) 10.5 and display phenotypes resembling severe maternal vitamin A deficiency, while Cyp26a1 and Cyp26b1 null embryos exhibit numerous malformations reminiscent of RA teratogenicity [3] [8].
Heterozygous mice have been shown to exhibit craniofacial malformations, such as anophthalmia/microphthalmia (absent or small eyes), short nose or agnathia/micrognathia (absent or small jaw; Matsuo et al., 1995).
This hypothesis has been further backed by the observation that MBNL1 knockout mice exhibit characteristic malformations similar to those of DM1, including the aberrant splicing pattern of several specific RNAs.
Hoxa13-null mice have agenesis of the caudal portion of the Müllerian duct, and Hoxd13 (homeobox D13 -null mice that also lack one copy of Hoxa13 exhibit severe malformations of the vagina anD13 -nulll genitalia, suggesting critical roles for these Hox gene paralogs in posterior FRT developmice (FromenthatRalson et alack996; Waroneet al. 1997).
The fetus exhibited skeletal malformations.
Altogether, the 140 newborns exhibited 175 malformations, corresponding to a prevalence rate of 0.7%.
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