Clinical Variability in a Family with an Ectodermal Dysplasia Syndrome and a Nonsense Mutation in the TP63 Gene.

Abstract

Mutations in the TP63 gene have been associated with a variety of ectodermal dysplasia syndromes, among which the clinically overlapping Ankyloblepharon-Ectodermal defects-Cleft lip/palate (AEC) and the Rapp-Hodgkin syndromes. We report a multiplex nonconsanguineous family of Ashkenazi-Jewish descent, in which the index patient presented with a persistent scalp skin lesion, dystrophic nails and light thin hair. Further evaluation revealed over 10 affected individuals in the kindred, over four generations, exhibiting varying degrees of ectodermal involvement. Analysis of the TP63 gene from four of the patients and from two healthy individuals of the same family was performed. Gene sequencing of the patients revealed a nonsense mutation leading to a premature termination codon (PTC) (p.Gln16X). The same mutation was found in all tested affected individuals in the family, but gave rise to marked phenotypic variability with minor clinical manifestations in some individuals, underscoring the clinical heterogeneity associated with the recently described PTC-causing mutations.

• Authors: Arik Eisenkraft, Ben Pode-Shakked, Nurit Goldstein, Zvi Shpirer, Hans van Bokhoven, Yair Anikster
• Journal: Fetal and pediatric pathology (Fetal Pediatr Pathol) Vol. 34 Issue 6 Pg. 400-6 ( 2015) ISSN: 1551-3823 [Electronic] England
• PMID: 26470833 (Publication Type: Case Reports, Journal Article)

Chemical References

• Codon, Nonsense
• TP63 protein, human
• Transcription Factors
• Tumor Suppressor Proteins

Topics

• Child, Preschool
• Codon, Nonsense
• DNA Mutational Analysis
• Ectodermal Dysplasia (genetics, pathology)
• Female
• Genotype
• Humans
• Male
• Pedigree
• Phenotype
• Polymerase Chain Reaction
• Transcription Factors (genetics)
• Tumor Suppressor Proteins (genetics)