Identification of novel variations in SLC6A8 and GAMT genes causing cerebral creatine deficiency syndrome.

• The use of NGS is an efficient technique to diagnose cerebral creatine deficiency syndrome precisely. • A combined mass spectrometry with gene mutation analysis is helpful in CCDS diagnosis. • Genetic diagnosis determined that all seven patients were positive for SLC6A8 or GAMT variation. • A total of 12 variants were identified in this cohort, including six novel ones. Cerebral creatine deficiency syndromes (CCDSs) are a group of rare mendelian disorders mainly characterized by intellectual disability, movement anomaly, behavior disorder and seizures. SLC6A8 , GAMT , and GATM are known genes responsible for CCDS. In this study, seven pediatric patients with developmental delay were recruited and submitted to a series of clinical evaluation, laboratory testing, and genetic analysis. The clinical manifestations and core biochemical indications of each child were basically consistent with the diagnosis of CCDS. Genetic diagnosis determined that all patients were positive for SLC6A8 or GAMT variation. A total of 12 variants were identified in this cohort, including six novel ones. The frequency of these variants, the Revel scores and the conservatism of the affected amino acids support their pathogenicity. Our findings expanded the mutation spectrum of CCDS disorders, and provided solid evidence for the counseling to affected families. [ABSTRACT FROM AUTHOR]