Identity-by-descent filtering of exome sequence data identifies PIGV mutations in hyperphosphatasia mental retardation syndrome.
Hyperphosphatasia mental retardation (HPMR) syndrome is an autosomal recessive form of mental retardation with distinct facial features and elevated serum alkaline phosphatase. We performed whole-exome sequencing in three siblings of a nonconsanguineous union with HPMR and performed computational inference of regions identical by descent in all siblings to establish PIGV, encoding a member of the GPI-anchor biosynthesis pathway, as the gene mutated in HPMR. We identified homozygous or compound heterozygous mutations in PIGV in three additional families.
Krawitz
Peter M
PM
Max Planck Institute for Molecular Genetics, Berlin, Germany. peter.robinson@charite.de
Schweiger
Michal R
MR
Rödelsperger
Christian
C
Marcelis
Carlo
C
Kölsch
Uwe
U
Meisel
Christian
C
Stephani
Friederike
F
Kinoshita
Taroh
T
Murakami
Yoshiko
Y
Bauer
Sebastian
S
Isau
Melanie
M
Fischer
Axel
A
Dahl
Andreas
A
Kerick
Martin
M
Hecht
Jochen
J
Köhler
Sebastian
S
Jäger
Marten
M
Grünhagen
Johannes
J
de Condor
Birgit Jonske
BJ
Doelken
Sandra
S
Brunner
Han G
HG
Meinecke
Peter
P
Passarge
Eberhard
E
Thompson
Miles D
MD
Cole
David E
DE
Horn
Denise
D
Roscioli
Tony
T
Mundlos
Stefan
S
Robinson
Peter N
PN
D000293:Adolescent; D000818:Animals; D016466:CHO Cells; D002675:Child, Preschool; D006224:Cricetinae; D003412:Cricetulus; D030541:Databases, Genetic; D005091:Exons / Q000235:genetics*; D005192:Family Health; D005260:Female; D020022:Genetic Predisposition to Disease; D017261:Glycosylphosphatidylinositols / Q000378:metabolism; D006801:Humans; D054559:Hyperphosphatemia / Q000235:genetics*; D007223:Infant; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D008364:Mannosyltransferases / Q000235:genetics*; D009154:Mutation / Q000235:genetics*; D016366:Open Reading Frames / Q000235:genetics; D013577:Syndrome; D014162:Transfection
D017261:Glycosylphosphatidylinositols; D008364:Mannosyltransferases; C553105:PIGV protein, human
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