Novel mutation in gene SLC6A8 causes cerebral creatine deficiency syndrome; a NGS clinical report

Introduction: Cerebral creatine deficiency syndrome-1 is an X-linked disorder of creatine (Cr) transport characterized by mental retardation, severe speech delay, behavioral abnormalities, and seizures. It has a prevalence of 0.3 to 3.5% in males. Carrier females may show mild neuropsychologic impairment.We report a male patient with developmental delay and hypotonia clinically evaluated and confirmed by NGS panels. Case report: A couple with consanguine marriage whom had two pregnancy including a dysmorphic child and a positive history for abortion in the second delivery. A child with severe neurologic disturbances including seizures, behavioral problems, speech delay, and inability to engage in structured play, as well as creatine deficiency. H-MRSI showed absence of creatine in the whole brain, which was not corrected by creatine supplementation. However there was not a definite clinical description but the preclinical findings and genetic counselling shows an XLR pattern of inheritance. Results: Chromosomal abnormalities was ruled out in parents and affected child so the Whole Exome Sequencing (WES) of the proband was done and the results annotated using genome data bases indicated that the child had a homozygous mutation in the SLC6A8 gene which was confirmed by sanger sequencing method. Conclusion:This mutation confirmed Cerebral creatine deficiency syndrome-1 as a final clinical description compatible with clinical signs described by neurologist.

Keywords:

SLC6A8 , Mutation , NGS , WES , XLR , Cerebral creatine deficiency syndrome-1