X-linked mental retardation with seizures and carrier manifestations is caused by a mutation in the creatine-transporter gene (SLC6A8) located in Xq28.
A family with X-linked mental retardation characterized by severe mental retardation, speech and behavioral abnormalities, and seizures in affected male patients has been found to have a G1141C transversion in the creatine-transporter gene SLC6A8. This mutation results in a glycine being replaced by an arginine (G381R) and alternative splicing, since the G-->C transversion occurs at the -1 position of the 5' splice junction of intron 7. Two female relatives who are heterozygous for the SLC6A8 mutation also exhibit mild mental retardation with behavior and learning problems. Male patients with the mutation have highly elevated creatine in their urine and have decreased creatine uptake in fibroblasts, which reflects the deficiency in creatine transport. The ability to measure elevated creatine in urine makes it possible to diagnose SLC6A8 deficiency in male patients with mental retardation of unknown etiology.
Hahn
Kimberly A
KA
Greenwood Genetic Center, Greenwood, SC 29646, USA.
Salomons
Gajja S
GS
Tackels-Horne
Darci
D
Wood
Tim C
TC
Taylor
Harold A
HA
Schroer
Richard J
RJ
Lubs
Herbert A
HA
Jakobs
Cornelis
C
Olson
Rick L
RL
Holden
Kenton R
KR
Stevenson
Roger E
RE
Schwartz
Charles E
CE
D000293:Adolescent; D000328:Adult; D000368:Aged; D017398:Alternative Splicing / Q000235:genetics; D000595:Amino Acid Sequence; D001483:Base Sequence; D004252:DNA Mutational Analysis; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000150:complications* / Q000235:genetics*; D007438:Introns / Q000235:genetics; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D012640:Seizures / Q000150:complications* / Q000235:genetics*; D014960:X Chromosome / Q000235:genetics*
D026901:Membrane Transport Proteins; C080679:creatine transporter