Early onset dystonia

Gene: GAMT

Red List (low evidence)

GAMT (guanidinoacetate N-methyltransferase)
EnsemblGeneIds (GRCh38): ENSG00000130005
EnsemblGeneIds (GRCh37): ENSG00000130005
OMIM: 601240, Gene2Phenotype
GAMT is in 11 panels

1 review

Eldar Dedic (Independent Clinical Genetics Consultant)

Green List (high evidence)

Dhar, et al. (2009, PMID: 19027335) presented 8 non-Portuguese GAMT deficiency cases. Sequencing of GAMT revealed c.402C>G (p.Tyr134*) variant in the compound heterozygous state with c.610_611delAGinsGAA (p.Arg204Glufs*63) variant in one 14 years of age male case (of Egyptian ethnicity) who also experienced dystonia (and showed normal brain MRI).

- Please note that, although GAMT c.610_611delAGinsGAA (p.Arg204Glufs*63) is absent from gnomAD v2.1.1, similar variant (GAMT c.609dup (p.Arg204Glufs*63)) is present with maximum minor allele frequency (MAX MAF) of 0.0008890% (1/112488; 0 homozygotes) in European (non-Finnish) population. The GAMT c.402C>G (p.Tyr134*) MAX MAF in gnomAD v2.1.1 is 0.003266% (1/30616; 0 homozygotes) in South Asian population

Modi, et al. (2021, PMID: 33996490) presented a consanguineous family with GAMT deficiency of Pakistani origin. Whole-exome-sequencing revealed homozygous GAMT c.134G>A (p.Trp45*) variant in 2 affected siblings who also had dystonia (age of onset 7 and 8 years, respectively). Sanger sequencing of additional family members revealed the presence of the same variant in 3 healthy family members (parents and sister) and the absence of the variant in a healthy brother.

- Please note that GAMT c.134G>A (p.Trp45*) is absent from gnmoAD v2.1.1 as of December 2021

Schulze, et al. (2003, PMID: 12557293) presented 26 years of age male with GAMT deficiency (whose parents were of Turkish origin). The GAMT sequencing revealed the presence of homozygous c.491dupG (p.Val165Argfs*26) variant in the case who also had dystonia (and normal cranial MRI).

- Please note that GAMT c.491dupG (p.Val165Argfs*26) is present in gnmoAD v2.1.1 with the MAX MAF of 0.01003% (2/19944; 0 homozygotes) in East Asian population

Engelke, et al. (2009, PMID: 19288536) presented 10 cases with GAMT deficiency. The homozygous GAMT c.324delC (p.His108Glnfs*6) has been reported in 4 siblings (age of 18, 23, 26, and 35 years, respectively) who had dystonia.

- Please note that GAMT c.324delC (p.His108Glnfs*6) is absent from gnmoAD v2.1.1 as of December 2021

Mercimek-Mahmutoglu, et al. (2006, PMID: 16855203) presented 27 GAMT deficiency cases. The GAMT variants were present in 3 cases with dystonia from 2 families: 29 years of age female patient and her 24 years of age sister (both of Kosovo origin) who carried homozygous c.64dupG (p.Ala22Glyfs*63) variant; 18 years of age female patient of Spanish origin who carried c.59G>C (p.Trp20Ser) variant in the compound heterozygous state with c.521G>A (p.Trp174*) variant.

- Please note that GAMT c.64dupG (p.Ala22Glyfs*63) was present in gnomAD v2.1.1 with MAX MAF of 0.003624% (1/27592; 0 homozygotes) in European (non-Finnish) population. The GAMT c.59G>C (p.Trp20Ser) had MAX MAF of 0.01094% (3/27420; 0 homozygotes) from European (non-Finnish) population. The GAMT c.521G>A (p.Trp174*) had MAX MAF of 0.006178% (7/113306; 0 homozygotes) from European (non-Finnish) population
Created: 7 Dec 2021, 3 p.m. | Last Modified: 7 Dec 2021, 3 p.m.
Panel Version: 1.99

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal


History Filter Activity

17 Oct 2016, Gel status: 1

panel promoted to version 1

Ellen McDonagh (Genomics England Curator)

17th Oct 2016: Promoted to version 1. The panel was revised after expert input and internal discussion with the clinical team. Other panels such as hereditary ataxia or dementia may be applied in conjunction with this panel where appropriate for genome analysis.

28 Apr 2015, Gel status: 1

Added New Source

GEL ()

GAMT was added to Early onset dystoniapanel. Sources: Emory Genetics Laboratory