Mutations of CASK cause an X-linked brain malformation phenotype with microcephaly and hypoplasia of the brainstem and cerebellum.
CASK is a multi-domain scaffolding protein that interacts with the transcription factor TBR1 and regulates expression of genes involved in cortical development such as RELN. Here we describe a previously unreported X-linked brain malformation syndrome caused by mutations of CASK. All five affected individuals with CASK mutations had congenital or postnatal microcephaly, disproportionate brainstem and cerebellar hypoplasia, and severe mental retardation.
Najm
Juliane
J
Institut für Humangenetik, Universitätsklinikum Hamburg-Eppendorf, 20246 Hamburg, Germany.
Horn
Denise
D
Wimplinger
Isabella
I
Golden
Jeffrey A
JA
Chizhikov
Victor V
VV
Sudi
Jyotsna
J
Christian
Susan L
SL
Ullmann
Reinhard
R
Kuechler
Alma
A
Haas
Carola A
CA
Flubacher
Armin
A
Charnas
Lawrence R
LR
Uyanik
Gökhan
G
Frank
Ulrich
U
Klopocki
Eva
E
Dobyns
William B
WB
Kutsche
Kerstin
K
D001933:Brain Stem / Q000002:abnormalities*; D002531:Cerebellum / Q000002:abnormalities*; D002675:Child, Preschool; D004423:Ear / Q000002:abnormalities; D005260:Female; D040181:Genetic Diseases, X-Linked / Q000235:genetics*; D051528:Guanylate Kinases / Q000235:genetics*; D006801:Humans; D008297:Male; D038901:X-Linked Intellectual Disability / Q000235:genetics; D008831:Microcephaly / Q000235:genetics*; D009154:Mutation; D000091042:Reelin Protein; D013577:Syndrome
D000091042:Reelin Protein; C106868:CASK kinases; D051528:Guanylate Kinases; C000717127:RELN protein, human