Spectrum of pathogenic variants and founder effects in amelogenesis imperfecta associated with MMP20
Autor: | Alan J. Mighell, Claire E. L. Smith, Suhaila Al-Bahlani, Mary J. O'Connell, Francesca Soldani, Peter F. Day, James A. Poulter, Gina Murillo, Georgios Nikolopoulos, Ian R. Berry, Sarah A. Harris, Teresa Lamb, Chris F. Inglehearn, Catriona J. Brown, Sandra Silva |
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Rok vydání: | 2021 |
Předmět: |
Amelogenesis Imperfecta
Biology Compound heterozygosity 03 medical and health sciences symbols.namesake stomatognathic system Genetics medicine Humans Amelogenesis imperfecta Genetics (clinical) Exome sequencing 030304 developmental biology 0303 health sciences MMP20 Homozygote 030305 genetics & heredity Haplotype Amelogenesis medicine.disease Founder Effect Pedigree Matrix Metalloproteinase 20 Mendelian inheritance symbols Founder effect |
Zdroj: | Human Mutation. 42:567-576 |
ISSN: | 1098-1004 1059-7794 |
Popis: | Amelogenesis imperfecta (AI) describes a heterogeneous group of developmental enamel defects that typically have Mendelian inheritance. Exome sequencing of ten families with recessive hypomaturation AI revealed 4 novel and 1 known variants in the matrix metallopeptidase 20 (MMP20) gene that were predicted to be pathogenic. MMP20 encodes a protease that cleaves the developing extracellular enamel matrix and is necessary for normal enamel crystal growth during amelogenesis. New homozygous missense changes were shared between four families of Pakistani heritage (c.625G>C; p.(Glu209Gln)) and two of Omani origin (c.710C>A; p.(Ser237Tyr)). In two families of UK origin and one from Costa Rica, affected individuals were homozygous for the previously reported c.954-2A>T; p.(Ile319Phefs*19) variant. For each of these variants, microsatellite haplotypes appeared to exclude a recent founder effect, but elements of haplotype were conserved, suggesting more distant founding ancestors. New compound heterozygous changes were identified in one family of European heritage; c.809_811+12delinsCCAG; p.(?) and c.1122A>C; p.(Gln374His). This report further elucidates the mutation spectrum of MMP20 and the probable impact on protein function, confirms a consistent hypomaturation phenotype and shows that mutations in MMP20 are a common cause of autosomal recessive AI in some communities. This article is protected by copyright. All rights reserved. |
Databáze: | OpenAIRE |
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