New missense variants in RELT causing hypomineralised amelogenesis imperfecta

Autor: Nikolopoulos, G, Smith, CEL, Brookes, SJ, El‐Asrag, ME, Brown, CJ, Patel, A, Murillo, G, O'Connell, MJ, Inglehearn, CF, Mighell, AJ
Jazyk: angličtina
Rok vydání: 2020
Předmět:
ISSN: 0009-9163
1399-0004
Popis: © 2020 The Authors. Clinical Genetics published by John Wiley & Sons Ltd. Amelogenesis imperfecta (AI) is a heterogeneous group of genetic diseases characterised by dental enamel malformation. Pathogenic variants in at least 33 genes cause syndromic or non-syndromic AI. Recently variants in RELT, encoding an orphan receptor in the tumour necrosis factor (TNF) superfamily, were found to cause recessive AI, as part of a syndrome encompassing small stature and severe childhood infections. Here we describe four additional families with autosomal recessive hypomineralised AI due to previously unreported homozygous mutations in RELT. Three families carried a homozygous missense variant in the fourth exon (c.164C>T, p.(T55I)) and a fourth family carried a homozygous missense variant in the 11th exon (c.1264C>T, p.(R422W)). We found no evidence of additional syndromic symptoms in affected individuals. Analyses of tooth microstructure with computerised tomography and scanning electron microscopy suggest a role for RELT in ameloblasts' coordination and interaction with the enamel matrix. Microsatellite genotyping in families segregating the T55I variant reveals a shared founder haplotype. These findings extend the RELT pathogenic variant spectrum, reveal a founder mutation in the UK Pakistani population and provide detailed analysis of human teeth affected by this hypomineralised phenotype, but do not support a possible syndromic presentation in all those with RELT-variant associated AI.
Databáze: OpenAIRE
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