Mutant CHUK and severe fetal encasement malformation.
We report an autosomal recessive lethal syndrome characterized by multiple fetal malformations, the most obvious anomalies being the defective face and seemingly absent limbs, which are bound to the trunk and encased under the skin. We identified the molecular defect that causes this syndrome, using a combined strategy of gene-expression arrays, candidate-gene analysis, clinical studies, and genealogic investigations. A point mutation in two affected fetuses led to the loss of the conserved helix–loop–helix ubiquitous kinase (CHUK), also known as IκB kinase α. CHUK has an essential role in the development of skin epidermis and its derivatives, along with various other morphogenetic events. (Funded by the Academy of Finland and others.).
National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki University Hospital, Helsinki, Finland.
Jenni
J
Lahtela
Heidi O
HO
Nousiainen
Vedran
V
Stefanovic
Jonna
J
Tallila
Heli
H
Viskari
Riitta
R
Karikoski
Massimiliano
M
Gentile
Carola
C
Saloranta
Teppo
T
Varilo
Riitta
R
Salonen
Marjo
M
Kestilä
D000015:Abnormalities, Multiple / Q000235:genetics*; D000818:Animals; D005145:Face / Q000002:abnormalities*; D015870:Gene Expression; D005808:Genes, Recessive; D006801:Humans; D051550:I-kappa B Kinase / Q000235:genetics*; D017880:Limb Deformities, Congenital / Q000235:genetics*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D010375:Pedigree; D017354:Point Mutation
C496559:CHUK protein, human; D051550:I-kappa B Kinase