Novel genetic variations in the SLC6A8 and GAMT genes

Abstract: 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.

ACD Summary: Shen et al. reported on the genetic analyses of 7 patients with CCDS. The children were between the ages of 2 and 8 years old and all had some form of intellectual disability or motor developmental delay. All patients had low creatine levels and genetic variations on either the SLC6A8 gene or GAMT gene. The authors noted that the definite type of CCDS for these 7 patients remains to be determined. With respect to the genetic testing, the authors identified 12 genetic variations in the 7 patients, with 6 of the variations being novel. The authors concluded that their data expands the spectrum of possible genetic variations underlying CCDS, which may help with future genetic counseling for families.

Parent Summary: Shen et al. reported on the genetic analyses of 7 patients with CCDS. The children were between the ages of 2 and 8 years old and all had some form of intellectual disability or motor developmental delay. All patients had low creatine levels and genetic variations on either the SLC6A8 gene or GAMT gene. The authors noted that the definite type of CCDS for these 7 patients remains to be determined. With respect to the genetic testing, the authors identified 12 genetic variations in the 7 patients, with 6 of the variations being novel. The authors concluded that their data expands the spectrum of possible genetic variations underlying CCDS, which may help with future genetic counseling for families.

Link to free article: Identification of novel variations in SLC6A8 and GAMT genes causing cerebral creatine deficiency syndrome

Link to PubMed: PubMed

Authors: Ming Shen, Guangming Yang, Zhehui Chen, Kai Yang, Hui Dong, Chengliang Yin, Yuxuan Cheng, Chunyan Zhang, Fangyan Gu, Yanling Yang, Yaping Tian

Key Terms: Multiple CCDS, clinical study, diagnostic, mutation study, pediatric patient