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Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome.
Genet Med. 2014 Sep; 16(9):720-4.GM

Abstract

PURPOSE

Treacher Collins syndrome is a mandibulofacial dysostosis caused by mutations in genes involved in ribosome biogenesis and synthesis. TCOF1 mutations are observed in ~80% of the patients and are inherited in an autosomal dominant manner. Recently, two other genes have been reported in <2% of patients--POLR1D in patients with autosomal dominant inheritance, and POLR1C in patients with autosomal recessive inheritance.

METHODS

We performed direct sequencing of TCOF1, POLR1C, and POLR1D in two unrelated consanguineous families.

RESULTS

The four affected children shared the same homozygous mutation in POLR1D (c.163C>G, p.Leu55Val). This mutation is localized in a region encoding the dimerization domain of the RNA polymerase. It is supposed that this mutation impairs RNA polymerase, resulting in a lower amount of mature dimeric ribosomes. A functional analysis of the transcripts of TCOF1 by real-time quantitative reverse transcription-polymerase chain reaction was performed in the first family, demonstrating a 50% reduction in the index case, compatible with this hypothesis.

CONCLUSION

This is the first report of POLR1D mutation being responsible for an autosomal recessive inherited Treacher Collins syndrome. These results reinforce the concept of genetic heterogeneity of Treacher Collins syndrome and underline the importance of combining clinical expertise and familial molecular analyses for appropriate genetic counseling.

Links

Publisher Full Text
linkinghub.elsevier.com
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Authors+Show Affiliations

Schaefer E
1] Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, CHU de Hautepierre, Strasbourg, France [2] Laboratoire de Génétique Médicale, INSERM U1112, Faculté de Médecine, Université de Strasbourg, Strasbourg, France.
Collet C
Service de Biochimie et de Biologie Moleculaire, Hôpital Lariboisière, INSERM U606, Assistance Publique-Hôpitaux de Paris, Paris, France.
Genevieve D
Service de Génétique Médicale, CHRU Montpellier, Université de Montpellier 1, Montpellier, France.
Vincent M
Service de Génétique Médicale, CHRU Montpellier, Université de Montpellier 1, Montpellier, France.
Lohmann DR
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
Sanchez E
Service de Génétique Médicale, CHRU Montpellier, Université de Montpellier 1, Montpellier, France.
Bolender C
Service de Pédiatrie, Centre Hospitalier de Haguenau, Haguenau, France.
Eliot MM
Service ORL, Hôpitaux Universitaires de Strasbourg, CHU de Hautepierre, Strasbourg, France.
Nürnberg G
Center for Genomics, University of Cologne, Cologne, Germany.
Passos-Bueno MR
Department of Genetics and Evolutive Biology, Human Genome Center, Institute of Bioscience, University of Sao Paulo, Sao Paulo, Brazil.
Wieczorek D
Institut für Humangenetik, Universitätsklinikum Essen, Universität Duisburg-Essen, Essen, Germany.
van Maldergem L
Centre de Génétique Humaine, Université de Franche-Comté, Besançon, France.
Doray B
1] Service de Génétique Médicale, Hôpitaux Universitaires de Strasbourg, CHU de Hautepierre, Strasbourg, France [2] Laboratoire de Génétique Médicale, INSERM U1112, Faculté de Médecine, Université de Strasbourg, Strasbourg, France [3] Current affiliation: Service de Génétique, CHU la Réunion, Hôpital Félix Guyon, Saint-Denis, France.

MeSH

AdultAmino Acid SubstitutionChildChild, PreschoolDNA Mutational AnalysisDNA-Directed RNA PolymerasesFaciesFemaleGene Expression RegulationGenes, RecessiveGenetic Association StudiesGenetic LociHaplotypesHomozygoteHumansMandibulofacial DysostosisMutationNuclear ProteinsPhenotypePhosphoproteinsRNA, Messenger

Pub Type(s)

Journal Article

Language

eng

PubMed ID

24603435

Citation

Schaefer, Elise, et al. "Autosomal Recessive POLR1D Mutation With Decrease of TCOF1 mRNA Is Responsible for Treacher Collins Syndrome." Genetics in Medicine : Official Journal of the American College of Medical Genetics, vol. 16, no. 9, 2014, pp. 720-4.
Schaefer E, Collet C, Genevieve D, et al. Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genet Med. 2014;16(9):720-4.
Schaefer, E., Collet, C., Genevieve, D., Vincent, M., Lohmann, D. R., Sanchez, E., Bolender, C., Eliot, M. M., Nürnberg, G., Passos-Bueno, M. R., Wieczorek, D., van Maldergem, L., & Doray, B. (2014). Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genetics in Medicine : Official Journal of the American College of Medical Genetics, 16(9), 720-4. https://doi.org/10.1038/gim.2014.12
Schaefer E, et al. Autosomal Recessive POLR1D Mutation With Decrease of TCOF1 mRNA Is Responsible for Treacher Collins Syndrome. Genet Med. 2014;16(9):720-4. PubMed PMID: 24603435.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. AU - Schaefer,Elise, AU - Collet,Corinne, AU - Genevieve,David, AU - Vincent,Marie, AU - Lohmann,Dietmar R, AU - Sanchez,Elodie, AU - Bolender,Chantal, AU - Eliot,Marie-Madeleine, AU - Nürnberg,Gudrun, AU - Passos-Bueno,Maria-Rita, AU - Wieczorek,Dagmar, AU - van Maldergem,Lionel, AU - Doray,Bérénice, Y1 - 2014/03/06/ PY - 2013/09/17/received PY - 2014/01/13/accepted PY - 2014/3/8/entrez PY - 2014/3/8/pubmed PY - 2015/5/23/medline SP - 720 EP - 4 JF - Genetics in medicine : official journal of the American College of Medical Genetics JO - Genet Med VL - 16 IS - 9 N2 - PURPOSE: Treacher Collins syndrome is a mandibulofacial dysostosis caused by mutations in genes involved in ribosome biogenesis and synthesis. TCOF1 mutations are observed in ~80% of the patients and are inherited in an autosomal dominant manner. Recently, two other genes have been reported in <2% of patients--POLR1D in patients with autosomal dominant inheritance, and POLR1C in patients with autosomal recessive inheritance. METHODS: We performed direct sequencing of TCOF1, POLR1C, and POLR1D in two unrelated consanguineous families. RESULTS: The four affected children shared the same homozygous mutation in POLR1D (c.163C>G, p.Leu55Val). This mutation is localized in a region encoding the dimerization domain of the RNA polymerase. It is supposed that this mutation impairs RNA polymerase, resulting in a lower amount of mature dimeric ribosomes. A functional analysis of the transcripts of TCOF1 by real-time quantitative reverse transcription-polymerase chain reaction was performed in the first family, demonstrating a 50% reduction in the index case, compatible with this hypothesis. CONCLUSION: This is the first report of POLR1D mutation being responsible for an autosomal recessive inherited Treacher Collins syndrome. These results reinforce the concept of genetic heterogeneity of Treacher Collins syndrome and underline the importance of combining clinical expertise and familial molecular analyses for appropriate genetic counseling. SN - 1530-0366 UR - https://www.unboundmedicine.com/medline/citation/24603435/Autosomal_recessive_POLR1D_mutation_with_decrease_of_TCOF1_mRNA_is_responsible_for_Treacher_Collins_syndrome_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1098-3600(21)04890-5 DB - PRIME DP - Unbound Medicine ER -