Rapp-Hodgkin ectodermal dysplasia syndrome: the clinical and molecular overlap with Hay-Wells syndrome.
We report on the clinical and molecular abnormalities in a 7-month-old girl and her mother with an ectodermal dysplasia disorder that most closely resembles Rapp-Hodgkin syndrome (RHS). At birth, the child had bilateral cleft palate, a narrow pinched nose, small chin, and hypoplastic nipples, and suffered from respiratory distress, feeding difficulties, and poor weight gain, although developmental progress was normal. Her mother had a cleft palate, sparse hair, high forehead, dental anomalies, a narrow nose, dysplastic nails, and reduced sweating. Sequencing of the p63 gene in genomic DNA from both individuals revealed a heterozygous frameshift mutation, 1721delC, in exon 14. This mutation has not been described previously and is the seventh report of a pathogenic p63 gene mutation in RHS. The frameshift results in changes to the tail of p63 with the addition of 90 missense amino acids downstream and a delayed termination codon that extends the protein by 21 amino acids. This mutation is predicted to disrupt the normal repressive function of the transactivation inhibitory domain leading to gain-of-function for at least two isoforms of the p63 transcription factor. The expanding p63 mutation database demonstrates that there is considerable overlap between the molecular pathology of RHS and Hay-Wells syndrome, with identical mutations in some cases, and that these two disorders may in fact be synonymous.
Kannu
Peter
P
Genetic Health Services Victoria, Flemington Road, Parkville, Australia. peter.kannu@ghsv.org.au
Savarirayan
Ravi
R
Ozoemena
Linda
L
White
Susan M
SM
McGrath
John A
JA
D000328:Adult; D015415:Biomarkers; D002680:Chin / Q000002:abnormalities; D002972:Cleft Palate / Q000235:genetics; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D016368:Frameshift Mutation; D006801:Humans; D007223:Infant; D008565:Membrane Proteins / Q000235:genetics; D009264:Nails, Malformed / Q000235:genetics; D009666:Nose / Q000002:abnormalities; D013577:Syndrome
D015415:Biomarkers; C081876:CKAP4 protein, human; D008565:Membrane Proteins