The Experts below are selected from a list of 231 Experts worldwide ranked by ideXlab platform
Ali O. Yildirim - One of the best experts on this subject based on the ideXlab platform.
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Viable Ednra ^ Y129F mice feature human Mandibulofacial Dysostosis with alopecia (MFDA) syndrome due to the homologue mutation
Mammalian Genome, 2016Co-Authors: Sibylle Sabrautzki, Michael A. Sandholzer, Bettina Lorenz-depiereux, Robert Brommage, Gerhard Przemeck, Ingrid L. Vargas Panesso, Alexandra Vernaleken, Lillian Garrett, Katharina Baron, Ali O. YildirimAbstract:Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene ( Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the Mandibulofacial Dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra ^Y129F mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA-affected individuals. As observed in MFDA-affected individuals, mutant Ednra ^Y129F mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra ^Y129F mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)–endothelin receptor type A (EDNRA) signaling. Above all, Ednra ^Y129F mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions.
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Viable Ednra (Y129F) mice feature human Mandibulofacial Dysostosis with alopecia (MFDA) syndrome due to the homologue mutation.
Mammalian genome : official journal of the International Mammalian Genome Society, 2016Co-Authors: Sibylle Sabrautzki, Michael A. Sandholzer, Bettina Lorenz-depiereux, Robert Brommage, Gerhard Przemeck, Alexandra Vernaleken, Lillian Garrett, Katharina Baron, Ingrid L. Vargas Panesso, Ali O. YildirimAbstract:Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene (Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the Mandibulofacial Dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra Y129F mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA-affected individuals. As observed in MFDA-affected individuals, mutant Ednra Y129F mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra Y129F mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)–endothelin receptor type A (EDNRA) signaling. Above all, Ednra Y129F mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions.
Sibylle Sabrautzki - One of the best experts on this subject based on the ideXlab platform.
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Viable Ednra ^ Y129F mice feature human Mandibulofacial Dysostosis with alopecia (MFDA) syndrome due to the homologue mutation
Mammalian Genome, 2016Co-Authors: Sibylle Sabrautzki, Michael A. Sandholzer, Bettina Lorenz-depiereux, Robert Brommage, Gerhard Przemeck, Ingrid L. Vargas Panesso, Alexandra Vernaleken, Lillian Garrett, Katharina Baron, Ali O. YildirimAbstract:Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene ( Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the Mandibulofacial Dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra ^Y129F mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA-affected individuals. As observed in MFDA-affected individuals, mutant Ednra ^Y129F mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra ^Y129F mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)–endothelin receptor type A (EDNRA) signaling. Above all, Ednra ^Y129F mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions.
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Viable Ednra (Y129F) mice feature human Mandibulofacial Dysostosis with alopecia (MFDA) syndrome due to the homologue mutation.
Mammalian genome : official journal of the International Mammalian Genome Society, 2016Co-Authors: Sibylle Sabrautzki, Michael A. Sandholzer, Bettina Lorenz-depiereux, Robert Brommage, Gerhard Przemeck, Alexandra Vernaleken, Lillian Garrett, Katharina Baron, Ingrid L. Vargas Panesso, Ali O. YildirimAbstract:Animal models resembling human mutations are valuable tools to research the features of complex human craniofacial syndromes. This is the first report on a viable dominant mouse model carrying a non-synonymous sequence variation within the endothelin receptor type A gene (Ednra c.386A>T, p.Tyr129Phe) derived by an ENU mutagenesis program. The identical amino acid substitution was reported recently as disease causing in three individuals with the Mandibulofacial Dysostosis with alopecia (MFDA, OMIM 616367) syndrome. We performed standardized phenotyping of wild-type, heterozygous, and homozygous Ednra Y129F mice within the German Mouse Clinic. Mutant mice mimic the craniofacial phenotypes of jaw dysplasia, micrognathia, dysplastic temporomandibular joints, auricular dysmorphism, and missing of the squamosal zygomatic process as described for MFDA-affected individuals. As observed in MFDA-affected individuals, mutant Ednra Y129F mice exhibit hearing impairment in line with strong abnormalities of the ossicles and further, reduction of some lung volumetric parameters. In general, heterozygous and homozygous mice demonstrated inter-individual diversity of expression of the craniofacial phenotypes as observed in MFDA patients but without showing any cleft palates, eyelid defects, or alopecia. Mutant Ednra Y129F mice represent a valuable viable model for complex human syndromes of the first and second pharyngeal arches and for further studies and analysis of impaired endothelin 1 (EDN1)–endothelin receptor type A (EDNRA) signaling. Above all, Ednra Y129F mice model the recently published human MFDA syndrome and may be helpful for further disease understanding and development of therapeutic interventions.
Gabriele Gillessenkaesbach - One of the best experts on this subject based on the ideXlab platform.
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microcephaly microtia preauricular tags choanal atresia and developmental delay in three unrelated patients a Mandibulofacial Dysostosis distinct from treacher collins syndrome
American Journal of Medical Genetics Part A, 2009Co-Authors: Dagmar Wieczorek, Blanca Gener, Ma Jesus Martinez Gonzalez, Saskia Seland, Sven Fischer, Ute Hehr, Alma Kuechler, Lies H Hoefsloot, Nicole De Leeuw, Gabriele GillessenkaesbachAbstract:Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined Mandibulofacial Dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other Mandibulofacial dysostoses (MDs) such as Toriello (OMIM 301950), Bauru (OMIM 604830), Hedera-Toriello-Petty (OMIM 608257), and Guion-Almeida (OMIM 610536) syndromes are less well characterized and much rarer. Here we describe three unrelated patients showing clinical features overlapping with TCS, but who in addition have developmental delay, microcephaly and a distinct facial gestalt. Because of the distinct ear anomalies and the hearing loss a HOXA2 mutation was taken into account. CHARGE syndrome was discussed because of ear anomalies, choanal atresia, and developmental delay in our patients. But mutational analyses including sequencing of the TCOF1, the HOXA2, and the CHD7 genes, deletion screening of the TCOF1 gene as well as genomewide array analyses revealed normal results. We suggest that these three patients have a new type of Mandibulofacial Dysostosis. As all three cases are sporadic and both sexes are affected the pattern of inheritance might be autosomal dominant or autosomal recessive. Identification of additional patients will allow to further delineate the phenotype, to assign the inheritance pattern and to identify the molecular basis.
David M. Sherer - One of the best experts on this subject based on the ideXlab platform.
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Prenatal sonographic diagnosis of Treacher Collins syndrome: a case and review of the literature.
American journal of perinatology, 1995Co-Authors: Jose Cohen, Fabio Ghezzi, Luis F. Gonçalves, José Fuentes, Kristin J. Paulyson, David M. ShererAbstract:We report the prenatal ultrasonographic diagnosis of a fetus with Mandibulofacial Dysostosis (Treacher Collins syndrome). Sonographic findings included : polyhydramnios, microcephaly, abnormal fetal facial features (slanting forehead, microphthalmos, micrognathia), and abnormal fetal swallowing. A review of the current literature pertaining to prenatal diagnosis of this condition is presented.
Blanca Gener - One of the best experts on this subject based on the ideXlab platform.
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Haploinsufficiency of a Spliceosomal GTPase Encoded by EFTUD2 Causes Mandibulofacial Dysostosis with Microcephaly
American journal of human genetics, 2012Co-Authors: Matthew A. Lines, Blanca Gener, Roseli Maria Zechi-ceide, Maria Leine Guion-almeida, Lijia Huang, Jeremy Schwartzentruber, Stuart Douglas, Danielle C. Lynch, Chandree L. Beaulieu, Gabriele Gillessen-kaesbachAbstract:Mandibulofacial Dysostosis with microcephaly (MFDM) is a rare sporadic syndrome comprising craniofacial malformations, microcephaly, developmental delay, and a recognizable dysmorphic appearance. Major sequelae, including choanal atresia, sensorineural hearing loss, and cleft palate, each occur in a significant proportion of affected individuals. We present detailed clinical findings in 12 unrelated individuals with MFDM; these 12 individuals compose the largest reported cohort to date. To define the etiology of MFDM, we employed whole-exome sequencing of four unrelated affected individuals and identified heterozygous mutations or deletions of EFTUD2 in all four. Validation studies of eight additional individuals with MFDM demonstrated causative EFTUD2 mutations in all affected individuals tested. A range of EFTUD2-mutation types, including null alleles and frameshifts, is seen in MFDM, consistent with haploinsufficiency; segregation is de novo in all cases assessed to date. U5-116kD, the protein encoded by EFTUD2, is a highly conserved spliceosomal GTPase with a central regulatory role in catalytic splicing and post-splicing-complex disassembly. MFDM is the first multiple-malformation syndrome attributed to a defect of the major spliceosome. Our findings significantly extend the range of reported spliceosomal phenotypes in humans and pave the way for further investigation in related conditions such as Treacher Collins syndrome.
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microcephaly microtia preauricular tags choanal atresia and developmental delay in three unrelated patients a Mandibulofacial Dysostosis distinct from treacher collins syndrome
American Journal of Medical Genetics Part A, 2009Co-Authors: Dagmar Wieczorek, Blanca Gener, Ma Jesus Martinez Gonzalez, Saskia Seland, Sven Fischer, Ute Hehr, Alma Kuechler, Lies H Hoefsloot, Nicole De Leeuw, Gabriele GillessenkaesbachAbstract:Treacher Collins syndrome (TCS, OMIM 154500) is a well-defined Mandibulofacial Dysostosis characterized by symmetric facial anomalies consisting of malar hypoplasia, coloboma of the lower eyelid, dysplastic ears, micrognathia, cleft palate and deafness. Other Mandibulofacial dysostoses (MDs) such as Toriello (OMIM 301950), Bauru (OMIM 604830), Hedera-Toriello-Petty (OMIM 608257), and Guion-Almeida (OMIM 610536) syndromes are less well characterized and much rarer. Here we describe three unrelated patients showing clinical features overlapping with TCS, but who in addition have developmental delay, microcephaly and a distinct facial gestalt. Because of the distinct ear anomalies and the hearing loss a HOXA2 mutation was taken into account. CHARGE syndrome was discussed because of ear anomalies, choanal atresia, and developmental delay in our patients. But mutational analyses including sequencing of the TCOF1, the HOXA2, and the CHD7 genes, deletion screening of the TCOF1 gene as well as genomewide array analyses revealed normal results. We suggest that these three patients have a new type of Mandibulofacial Dysostosis. As all three cases are sporadic and both sexes are affected the pattern of inheritance might be autosomal dominant or autosomal recessive. Identification of additional patients will allow to further delineate the phenotype, to assign the inheritance pattern and to identify the molecular basis.