Carrier frequency of guanidinoacetate methyltransferase deficiency in the general population by functional characterization of missense variants in the GAMT gene

Abstract: To determine carrier frequency of GAMT deficiency, we studied the variants in the GAMT gene reported in the Exome Variant Server database and performed functional characterization of missense variants. We used previously cloned GAMT transcript variant 1 (7 missense variants) and cloned a novel GAMT transcript variant 2 (5 missense variants). The latter was used in Exome Variant Server database according to recommendations of the Human Genome Variation Society. There were 4 missense variants (1 previously reported and 3 novel) with low GAMT enzyme activity indicating pathogenicity. We concluded that GAMT transcript variant 2 is not involved in GAMT protein synthesis. For this reason, Human Genome Variation Society should use mutation nomenclature according to the coding region of the GAMT transcript variant 1. The carrier frequency of GAMT deficiency was 0.123 % in the general population. GAMT deficiency should be included in newborn screening programs to diagnose individuals at the asymptomatic stage of the disease to prevent permanent neurodevelopmental disability.
Findings: c.500C>T; p.Thr167Ile 15% of normal activity, c.467C>G; p.Ala156Arg 5% of normal activity

Link to article: https://link.springer.com/article/10.1007/s00438-015-1067-x

PubMed:  https://pubmed.ncbi.nlm.nih.gov/26003046/

Authors: Caro‐Lyne Desroches, Jaina Patel, Peixiang Wang, Berge Minassian, Christian R. Marshall, Gajja S. Salomons, Saadet Mercimek‐Mahmutoglu

Key Terms: GAMT, Mutation Study, Diagnostic, NBS, Clinical Study, Pediatric Patient