TY  - JOUR
AU  - Hengel, H.
AU  - Keimer, R.
AU  - Deigendesch, W.
AU  - Rieß, A.
AU  - Marzouqa, H.
AU  - Zaidan, J.
AU  - Bauer, P.
AU  - Schöls, L.
TI  - GPT2 mutations cause developmental encephalopathy with microcephaly and features of complicated hereditary spastic paraplegia.
JO  - Clinical genetics
VL  - 94
IS  - 3-4
SN  - 0009-9163
CY  - Malden, Mass.
PB  - Wiley
M1  - DZNE-2020-06514
SP  - 356-361
PY  - 2018
AB  - Various genetic defects can cause intellectual and developmental disabilities (IDDs). Often IDD is a symptom of a more complex neurodevelopmental or neurodegenerative syndrome. Identifying syndromic patterns is substantive for diagnostics and for understanding the pathomechanism of a disease. Recessive glutamate pyruvate transaminase (GPT2) mutations have recently been associated with IDD in 4 families. Here, we report a novel recessive GPT2 stop mutation p.Gln24* causing a complex IDD phenotype in a homozygous state in 5 patients from 2 consanguineous Arab families. By compiling clinical information of these individuals and previously described GPT2 patients a recognizable neurodevelopmental and potentially neurodegenerative phenotype can be assigned consisting of intellectual disability, pyramidal tract affection with spastic paraplegia, microcephaly and frequently epilepsy. Because of the consistent presence of pyramidal tract affection in GPT2 patients, we further suggest that GPT2 mutations should be considered in cases with complex hereditary spastic paraplegia.
KW  - Adolescent
KW  - Adult
KW  - Brain Diseases: genetics
KW  - Child
KW  - Consanguinity
KW  - Female
KW  - Humans
KW  - Male
KW  - Mutation
KW  - Pedigree
KW  - Spastic Paraplegia, Hereditary: genetics
KW  - Transaminases: genetics
KW  - GPT2 protein, human (NLM Chemicals)
KW  - Transaminases (NLM Chemicals)
LB  - PUB:(DE-HGF)16
C6  - pmid:29882329
DO  - DOI:10.1111/cge.13390
UR  - https://pub.dzne.de/record/140192
ER  -