Rapp-Hodgkin syndrome and SHFM1 patients: delineating the p63-Dlx5/Dlx6 pathway

Gene
Ascensión Vera-CarbonellIsabel López-Expósito

Abstract

Rapp-Hodgkin Syndrome (RHS) is a genetic disorder resulting from mutations in the TP63 gene encoding p63 transcription factor. p63 is directly associated with a cis-regulatory element on chromosome 7q21 that controls the expression of DLX5 and DLX6 genes which are involved in craniofacial abnormalities and ectrodactyly or split hand/foot malformation (SHFM). Chromosomal deletions on 7q21 locus can result in loss of DXL5/DLX6 and/or in loss/disruption of cis-regulatory elements, at which p63 binds. We report two patients that have in common a p63-Dlx5/Dlx6 pathway dysregulation. One showed growth retardation, craniofacial dysmorphism, syndactyly, developmental delay and a de novo deletion (~8.5Mb) on chromosome 7q21.13-q21.3, including DLX5 and DLX6. The second patient with a clinical diagnosis of RHS showed a de novo heterozygous missense mutation, c. 401G>A (p.G134D), in TP63 (exon 4). Our findings may contribute to a greater understanding of the pathogenic mechanisms underlying disorders caused by TP63 mutations.

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Citations

Feb 4, 2016·Human Genetics·Malene B RasmussenNanna D Rendtorff
Jun 15, 2013·The International Journal of Biochemistry & Cell Biology·Cécile PolgeDaniel Taillandier
Feb 1, 2019·American Journal of Medical Genetics. Part a·John Timothy WrightMaria I Morasso
Feb 18, 2016·Clinical Dysmorphology·Felix B Brueggemann, Oliver Bartsch
Jan 1, 2020·Scientific Reports·Laurène Alicia LecaudeyEhsan Pashay Ahi

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