Mutations in SPINK5, encoding a serine protease inhibitor, cause Netherton syndrome.
We describe here eleven different mutations in SPINK5, encoding the serine protease inhibitor LEKTI, in 13 families with Netherton syndrome (NS, MIM256500). Most of these mutations predict premature termination codons. These results disclose a critical role of SPINK5 in epidermal barrier function and immunity, and suggest a new pathway for high serum IgE levels and atopic manifestations.
Chavanas
S
S
The Wellcome Trust Centre for Human Genetics, University of Oxford, Oxford, UK.
Bodemer
C
C
Rochat
A
A
Hamel-Teillac
D
D
Ali
M
M
Irvine
A D
AD
Bonafé
J L
JL
Wilkinson
J
J
Taïeb
A
A
Barrandon
Y
Y
Harper
J I
JI
de Prost
Y
Y
Hovnanian
A
A
D000015:Abnormalities, Multiple / Q000235:genetics*; D000595:Amino Acid Sequence; D001483:Base Sequence; D002352:Carrier Proteins; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics; D018388:Codon, Terminator / Q000235:genetics; D004252:DNA Mutational Analysis; D005091:Exons / Q000235:genetics; D016368:Frameshift Mutation / Q000235:genetics; D005808:Genes, Recessive / Q000235:genetics; D006801:Humans; D007438:Introns / Q000235:genetics; D009154:Mutation / Q000235:genetics*; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors / Q000235:genetics*; D013577:Syndrome
D002352:Carrier Proteins; D018388:Codon, Terminator; D053491:Proteinase Inhibitory Proteins, Secretory; D012333:RNA, Messenger; C120650:SPINK5 protein, human; D000074163:Serine Peptidase Inhibitor Kazal-Type 5; D015842:Serine Proteinase Inhibitors