Universität zu Köln

Schaefer, Elise, Collet, Corinne, Genevieve, David, Vincent, Marie ORCID: 0000-0003-1010-5618, Lohmann, Dietmar R. ORCID: 0000-0002-2624-9889, Sanchez, Elodie, Bolender, Chantal, Eliot, Marie-Madeleine, Nuernberg, Gudrun, Passos-Bueno, Maria-Rita, Wieczorek, Dagmar ORCID: 0000-0003-2812-6492, Van Maldergem, Lionel ORCID: 0000-0001-8880-5214 and Doray, Berenice (2014). Autosomal recessive POLR1D mutation with decrease of TCOF1 mRNA is responsible for Treacher Collins syndrome. Genet. Med., 16 (9). S. 720 - 725. NEW YORK: NATURE PUBLISHING GROUP. ISSN 1530-0366

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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 similar to 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.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Schaefer, Elise UNSPECIFIED UNSPECIFIED UNSPECIFIED Collet, Corinne UNSPECIFIED UNSPECIFIED UNSPECIFIED Genevieve, David UNSPECIFIED UNSPECIFIED UNSPECIFIED Vincent, Marie UNSPECIFIED orcid.org/0000-0003-1010-5618 UNSPECIFIED Lohmann, Dietmar R. UNSPECIFIED orcid.org/0000-0002-2624-9889 UNSPECIFIED Sanchez, Elodie UNSPECIFIED UNSPECIFIED UNSPECIFIED Bolender, Chantal UNSPECIFIED UNSPECIFIED UNSPECIFIED Eliot, Marie-Madeleine UNSPECIFIED UNSPECIFIED UNSPECIFIED Nuernberg, Gudrun UNSPECIFIED UNSPECIFIED UNSPECIFIED Passos-Bueno, Maria-Rita UNSPECIFIED UNSPECIFIED UNSPECIFIED Wieczorek, Dagmar UNSPECIFIED orcid.org/0000-0003-2812-6492 UNSPECIFIED Van Maldergem, Lionel UNSPECIFIED orcid.org/0000-0001-8880-5214 UNSPECIFIED Doray, Berenice UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-430139
DOI:	10.1038/gim.2014.12
Journal or Publication Title:	Genet. Med.
Volume:	16
Number:	9
Page Range:	S. 720 - 725
Date:	2014
Publisher:	NATURE PUBLISHING GROUP
Place of Publication:	NEW YORK
ISSN:	1530-0366
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language GENE; TRANSCRIPTION Multiple languages Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43013