title: Rapp-Hodgkin syndrome and SHFM1 patients: delineating the p63-Dlx5/Dlx6 pathway.
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.
authors.affiliation: Centro de Bioquímica y Genética Clínica, Hospital U. Virgen de la Arrixaca, Murcia, Spain.
authors.forename: Ascensión
authors.initials: A
authors.lastname: Vera-Carbonell
authors.forename: María Rosa
authors.initials: MR
authors.lastname: Moya-Quiles
authors.forename: María
authors.initials: M
authors.lastname: Ballesta-Martínez
authors.forename: Vanesa
authors.initials: V
authors.lastname: López-González
authors.forename: Juan Antonio
authors.initials: JA
authors.lastname: Bafallíu
authors.forename: Encarna
authors.initials: E
authors.lastname: Guillén-Navarro
authors.forename: Isabel
authors.initials: I
authors.lastname: López-Expósito
mesh_terms: D000293:Adolescent; D002675:Child, Preschool; D002872:Chromosome Deletion; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D002971:Cleft Lip / Q000235:genetics* / Q000378:metabolism; D002972:Cleft Palate / Q000235:genetics* / Q000378:metabolism; D019465:Craniofacial Abnormalities / Q000235:genetics / Q000378:metabolism; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000378:metabolism; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000378:metabolism; D008297:Male; D020125:Mutation, Missense / Q000235:genetics; D046988:Proteasome Endopeptidase Complex / Q000235:genetics*; D017384:Sequence Deletion / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics* / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C100596:DLX5 protein, human; C491014:DLX6 protein, human; D018398:Homeodomain Proteins; C484606:SEM1 protein, human; C115051:TP63 protein, human; D014157:Transcription Factors; D025521:Tumor Suppressor Proteins; D046988:Proteasome Endopeptidase Complex