Novel homozygous mutation, c.400C>T (p.Arg134*), in the PVRL1 gene underlies cleft lip/palate-ectodermal dysplasia syndrome in an Asian patient.
Cleft lip/palate-ectodermal dysplasia syndrome is a rare, autosomal recessive disorder caused by homozygous loss-of-function mutations of the poliovirus receptor-like 1 (PVRL1) gene encoding nectin-1. Nectin-1 is a cell-cell adhesion molecule that is important for the initial step in the formation of adherens junctions and tight junctions; it is expressed in keratinocytes, neurons, and the developing face and palate. Clinical manifestations comprise a unique facial appearance with cleft lip/palate, ectodermal dysplasia, cutaneous syndactyly of the fingers and/or toes, and in some cases, mental retardation. We present the first report, to our knowledge, of an Asian individual with cleft lip/palate-ectodermal dysplasia syndrome with a novel PVRL1 mutation. A 7-year-old Japanese boy, the first child of a consanguineous marriage, showed hypohidrotic ectodermal dysplasia with sparse, brittle, fine, dry hair and hypodontia, the unique facial appearance with cleft lip/palate, cutaneous syndactyly of the fingers and mild mental retardation. Scanning electron microscopic examination of the hair demonstrated pili torti and pili trianguli et canaliculi. Mutation analysis of exon 2 of PVRL1 revealed a novel homozygous nonsense mutation, c.400C>T (p.Arg134*). His parents were heterozygous for the mutant alleles. All four PVRL1 mutations identified in cleft lip/palate-ectodermal dysplasia syndrome to date, including this study, resulted in truncated proteins that lack the transmembrane domain and intracellular domain of nectin-1, which is necessary to initiate the cell-cell adhesion process.
Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
Kazue
K
Yoshida
Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Ryota
R
Hayashi
Department of Medical Genetics, National Center for Child Health and Development, Tokyo, Japan.
Hideki
H
Fujita
Department of Neurology, National Center for Child Health and Development, Tokyo, Japan.
Masaya
M
Kubota
Department of Allergy, National Center for Child Health and Development, Tokyo, Japan.
Mai
M
Kondo
Laboratory of Genetic Skin Diseases, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
Yutaka
Y
Shimomura
Department of Dermatology, National Center for Child Health and Development, Tokyo, Japan.
Hironori
H
Niizeki
D015815:Cell Adhesion Molecules / Q000235:genetics*; D002648:Child; D002972:Cleft Palate / Q000235:genetics*; D018389:Codon, Nonsense; D004476:Ectodermal Dysplasia / Q000235:genetics*; D005260:Female; D006720:Homozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D007564:Japan; D008297:Male; D000075983:Nectins; D010375:Pedigree; D013576:Syndactyly / Q000235:genetics*
D015815:Cell Adhesion Molecules; D018389:Codon, Nonsense; C000619010:NECTIN1 protein, human; D000075983:Nectins
PVRL1; adherens junction; cleft lip/palate-ectodermal dysplasia syndrome; ectodermal dysplasia; nectin-1