Adaptor protein complex-4 (AP-4) deficiency causes a novel autosomal recessive cerebral palsy syndrome with microcephaly and intellectual disability.
BACKGROUND
Cerebral palsy is a heterogeneous group of neurodevelopmental brain disorders resulting in motor and posture impairments often associated with cognitive, sensorial, and behavioural disturbances. Hypoxic-ischaemic injury, long considered the most frequent causative factor, accounts for fewer than 10% of cases, whereas a growing body of evidence suggests that diverse genetic abnormalities likely play a major role.


RESULTS
This report describes an autosomal recessive form of spastic tetraplegic cerebral palsy with profound intellectual disability, microcephaly, epilepsy and white matter loss in a consanguineous family resulting from a homozygous deletion involving AP4E1, one of the four subunits of the adaptor protein complex-4 (AP-4), identified by chromosomal microarray analysis.


CONCLUSIONS
These findings, along with previous reports of human and mouse mutations in other members of the complex, indicate that disruption of any one of the four subunits of AP-4 causes dysfunction of the entire complex, leading to a distinct 'AP-4 deficiency syndrome'.
Department of Human Genetics, Emory University School of Medicine, Atlanta, Georgia, USA.
Andres
A
Moreno-De-Luca
Sandra L
SL
Helmers
Hui
H
Mao
Thomas G
TG
Burns
Amanda M A
AM
Melton
Karen R
KR
Schmidt
Paul M
PM
Fernhoff
David H
DH
Ledbetter
Christa L
CL
Martin
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D033964:Adaptor Protein Complex 4 / Q000172:deficiency* / Q000235:genetics; D002547:Cerebral Palsy / Q000235:genetics* / Q000473:pathology; D005808:Genes, Recessive; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D008607:Intellectual Disability / Q000235:genetics* / Q000473:pathology; D046228:Microarray Analysis; D008831:Microcephaly / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D013577:Syndrome
D033964:Adaptor Protein Complex 4