De novo enhancer deletion of LMX1B produces a mild nail-patella clinical phenotype.

Autor: Francis D; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia., Lall P; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia., Ayres S; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Parkville, Australia., Van Bergen NJ; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Parkville, Australia.; Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Parkville, Australia., Christodoulou J; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Parkville, Australia.; Brain and Mitochondrial Research Group, Murdoch Children's Research Institute, Parkville, Australia., Brown NJ; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Parkville, Australia., Kalitsis P; Victorian Clinical Genetics Services, Murdoch Children's Research Institute, Parkville, Australia.; Department of Paediatrics, University of Melbourne, The Royal Children's Hospital, Parkville, Australia.
Jazyk: angličtina
Zdroj: Clinical genetics [Clin Genet] 2024 Feb; Vol. 105 (2), pp. 214-219. Date of Electronic Publication: 2023 Oct 29.
DOI: 10.1111/cge.14447
Abstrakt: Critical genes involved in embryonic development are often transcription factors, regulating many downstream genes. LMX1B is a homeobox gene that is involved in formation of the limbs, eyes and kidneys, heterozygous loss-of-function sequence variants and deletions cause Nail-Patella syndrome. Most of the reported variants are localised within the gene's coding sequence, however, approximately 5%-10% of affected individuals do not have a pathogenic variant identified within this region. In this study, we present a family with four affected individuals across two generations with a deletion spanning a conserved upstream LMX1B-binding sequence. This deletion is de novo in the mother of three affected children. Furthermore, in this family, the manifestations appear limited to the nails and limbs, and therefore may reflect an attenuated phenotype of the classic Nail-Patella phenotype that includes ophthalmological and renal manifestations.
(© 2023 The Authors. Clinical Genetics published by John Wiley & Sons Ltd.)
Databáze: MEDLINE
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