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

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• 作者：Ascensió ; n Vera-Carbonell^a ; Marí ; a Rosa Moya-Quiles^b ; Marí ; a Ballesta-Martí ; nez^c ; Vanesa Ló ; pez-Gonzá ; lez^c ; Juan Antonio Bafallí ; u^a ; Encarna Guill&eacute ; n-Navarro^c ; Isabel Ló ; pez-Expó ; sito^a ; ^{isabel.lopez4@carm.es}
• 关键词：TP63 ; tumor protein p63 ; DLX ; distal-less homeobox ; AER ; apical ectodermal ridge ; DBD ; DNA-binding domain ; ISO ; isomerization ; TA ; transactivation ; SAM ; sterile alpha motif ; TI ; transactivation inhibitory ; EEC ; ectrodactyly&ndash ; ectodermal dysplasia&ndas
• 刊名：Gene
• 出版年：2012
• 期刊代码：73_03781119
• 类别：bio
• 出版时间：15 April, 2012
• 卷：497
• 期：2
• 页码：292-297
• 文件大小：619 K

摘要

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 (~ 8.5 Mb) 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.