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.).
Lahtela
Jenni
J
National Institute for Health and Welfare, Public Health Genomics Unit, Helsinki University Hospital, Helsinki, Finland.
Nousiainen
Heidi O
HO
Stefanovic
Vedran
V
Tallila
Jonna
J
Viskari
Heli
H
Karikoski
Riitta
R
Gentile
Massimiliano
M
Saloranta
Carola
C
Varilo
Teppo
T
Salonen
Riitta
R
Kestilä
Marjo
M
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