Poulter, JA, Smith, CEL, Murrillo, G et al. (9 more authors) (2015) A distinctive oral phenotype points to FAM20A mutations not identified by Sanger sequencing. Molecular Genetics & Genomic Medicine, 3 (6). pp. 543-549.
Abstract
Biallelic FAM20A mutations cause two conditions where Amelogenesis Imperfecta (AI) is the presenting feature: Amelogenesis Imperfecta and Gingival Fibromatosis Syndrome; and Enamel Renal Syndrome. A distinctive oral phenotype is shared in both conditions. On Sanger sequencing of FAM20A in cases with that phenotype, we identified two probands with single, likely pathogenic heterozygous mutations. Given the recessive inheritance pattern seen in all previous FAM20A mutation-positive families and the potential for renal disease, further screening was carried out to look for a second pathogenic allele. Reverse transcriptase-PCR on cDNA was used to determine transcript levels. CNVseq was used to screen for genomic insertions and deletions. In one family, FAM20A cDNA screening revealed only a single mutated FAM20A allele with the wild-type allele not transcribed. In the second family, CNV detection by whole genome sequencing (CNVseq) revealed a heterozygous 54.7 kb duplication encompassing exons 1 to 4 of FAM20A. This study confirms the link between biallelic FAM20A mutations and the characteristic oral phenotype. It highlights for the first time examples of FAM20A mutations missed by the most commonly used mutation screening techniques. This information informed renal assessment and ongoing clinical care.
Metadata
Item Type: | Article |
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Authors/Creators: |
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Copyright, Publisher and Additional Information: | © 2015 The Authors. This is an open access article under the terms of the Creative Commons Attribution License (CC-BY 4.0), which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
Keywords: | Amelogenesis imperfecta; CNVseq; namel renal syndrome; FAM20A |
Dates: |
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Institution: | The University of Leeds |
Academic Units: | The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Dentistry (Leeds) > Oral Surgery (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > School of Medicine (Leeds) > Inst of Biomed & Clin Sciences (LIBACS) (Leeds) > Genetics (LIBACS) (Leeds) The University of Leeds > Faculty of Medicine and Health (Leeds) > Institute of Molecular Medicine (LIMM) (Leeds) > Section of Opthalmology and Neurosciences (Leeds) |
Depositing User: | Symplectic Publications |
Date Deposited: | 18 Jun 2015 14:33 |
Last Modified: | 12 May 2016 08:44 |
Published Version: | https://dx.doi.org/10.1002/mgg3.164 |
Status: | Published |
Publisher: | Wiley |
Identification Number: | 10.1002/mgg3.164 |
Open Archives Initiative ID (OAI ID): | oai:eprints.whiterose.ac.uk:87174 |