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Vianna F.S.L.,INAGEMP National Institute of Population Medical Genetics | Vianna F.S.L.,Hospital Of Clinicas2De Porto Alegre | Vianna F.S.L.,Federal University of Rio Grande do Sul | Schuler-Faccini L.,INAGEMP National Institute of Population Medical Genetics | And 10 more authors.
Clinical Dysmorphology | Year: 2013

Thalidomide is the best-known teratogen worldwide. It was first marketed as a sedative in the late 1950s, but the birth of ∼10 000 children with birth defects resulted in the withdrawal of thalidomide from the market in 1962. Thalidomide embryopathy affects almost all organs but the main defects are concentrated in the limbs, eyes, ears, and heart. Shortly after the withdrawal of thalidomide from the market, its effectiveness in the treatment of erythema nodosum leprosum, an inflammatory condition resulting from leprosy, was reported and since the mid-1990s, the drug has been used widely in the treatment of cancers and autoimmune diseases, among other conditions. 40 000 new cases of leprosy are diagnosed every year in Brazil. Although there is a strict legislation for the prescription and use of thalidomide in Brazil, cases of thalidomide embryopathy have continued to be reported. Here, we present two new cases of thalidomide embryopathy identified in 2011 and review the major clinical findings in the literature that can aid the identification of the embryopathy. © 2013 Wolters Kluwer Health | Lippincott Williams & Wilkins.


Leslie E.J.,University of Pittsburgh | Liu H.,University of Iowa | Liu H.,Hubei University of Education | Carlson J.C.,University of Pittsburgh | And 62 more authors.
American Journal of Human Genetics | Year: 2016

Cleft palate (CP) is a common birth defect occurring in 1 in 2,500 live births. Approximately half of infants with CP have a syndromic form, exhibiting other physical and cognitive disabilities. The other half have nonsyndromic CP, and to date, few genes associated with risk for nonsyndromic CP have been characterized. To identify such risk factors, we performed a genome-wide association study of this disorder. We discovered a genome-wide significant association with a missense variant in GRHL3 (p.Thr454Met [c.1361C>T]; rs41268753; p = 4.08 × 10-9) and replicated the result in an independent sample of case and control subjects. In both the discovery and replication samples, rs41268753 conferred increased risk for CP (OR = 8.3, 95% CI 4.1-16.8; OR = 2.16, 95% CI 1.43-3.27, respectively). In luciferase transactivation assays, p.Thr454Met had about one-third of the activity of wild-type GRHL3, and in zebrafish embryos, perturbed periderm development. We conclude that this mutation is an etiologic variant for nonsyndromic CP and is one of few functional variants identified to date for nonsyndromic orofacial clefting. This finding advances our understanding of the genetic basis of craniofacial development and might ultimately lead to improvements in recurrence risk prediction, treatment, and prognosis. © 2016 The American Society of Human Genetics. All rights reserved.


PubMed | Ophir Loyola Hospital, INAGEMP National Institute of Population Medical Genetics, Federal University of Rio de Janeiro, In memoriam ECLAMC at Hospital Zonal El Bolson and 2 more.
Type: Journal Article | Journal: European journal of oral sciences | Year: 2016

Increased susceptibility to cleft lip, with or without cleft palate (CLP) has been observed in South America, as related to Amerindian ancestry, using epidemiological data, uniparental markers, and blood groups. In this study, it was evaluated whether this increased risk remains when Amerindian ancestry is estimated using autosomal markers and considered in the predictive model. Ancestry was estimated through genotyping 62 insertion and deletion (INDEL) markers in sample sets of patients with CLP, patients with cleft palate (CP), and controls, from Patagonia in southern Argentina and Belm in northern Brazil. The Amerindian ancestry in patients from Patagonia with CLP was greater than in controls although it did not reach statistical significance. The European ancestry in patients with CLP from Belm and in patients with CP from Belm and Patagonia was higher than in controls and statistically significant for patients with CP who were from Belm. This high contribution of European genetic ancestry among patients with CP who were from Belm has not been previously observed in American populations. Our results do not corroborate the currently accepted risks for CLP and CP estimated by epidemiological studies in the North American populations and probably reflect the higher admixture found in South American ethnic groups when compared with the same ethnic groups from the North American populations.

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