Ectodermal dysplasia-skin fragility syndrome due to a new homozygous internal deletion mutation in the PKP1 gene.
Ectodermal dysplasia-skin fragility syndrome (ED-SFS) is a rare autosomal recessive genodermatosis resulting from mutations in the PKP1 gene, encoding the desmosomal plaque protein plakophilin-1 (PKP1). Mutations in PKP1 may manifest with skin fragility and erosions, patches of scale crust on the trunk and limbs, peri-oral cracking and inflammation, hypotrichosis, palmoplantar keratoderma with painful fissuring and other somewhat variable ectodermal anomalies. Ten cases of the syndrome have been reported. We report a further case of this desmosomal genodermatosis. A 14-month old child, born to consanguineous parents, presented with a history of neonatal bullae and subsequent development of dystrophic nails, sparse eyelashes and eyebrows, woolly scalp hair, abnormal dental development and a desquamating erythematous rash at sites of trauma. A clinical diagnosis of ED-SFS was supported by skin biopsy findings of suprabasal intraepidermal clefting and a loss of immunoreactivity for PKP1. Sequencing of genomic DNA revealed a homozygous 5 base pair deletion in exon 5 of the PKP1 gene, designated c.897del5 (CAACC). This new mutation creates a frameshift, leading to a downstream premature termination codon, p.Pro299fsX61. This case highlights the clinicopathological consequences of inherited mutations in the PKP1 gene and illustrates the key role of desmosomes in skin biology.
Peter MacCallum Cancer Centre, Melbourne, Victoria, Australia. aaroneboyce@yahoo.com.au
Aaron E
AE
Boyce
John A
JA
McGrath
Tanasit
T
Techanukul
Dédée F
DF
Murrell
Chung Wo
CW
Chow
Lesley
L
McGregor
Lachlan J
LJ
Warren
D001483:Base Sequence; D004476:Ectodermal Dysplasia / Q000235:genetics* / Q000473:pathology; D005260:Female; D006720:Homozygote; D006801:Humans; D007223:Infant; D051191:Plakophilins / Q000235:genetics*; D017384:Sequence Deletion; D012871:Skin Diseases / Q000235:genetics* / Q000473:pathology
D051191:Plakophilins