Comment on list classification: New gene added by Zornitza Stark. Based on the available evidence there is currently not enough evidence to support a gene-disease assocation; therefore, this gene has been given an Amber rating.
Created: 7 Oct 2020, 1:07 p.m. | Last Modified: 7 Oct 2020, 1:07 p.m.
Panel Version: 2.17
Homozygous and compound heterozygous variants (missense, nonsense and frameshift) found in 8 Japanese patients from unrelated families with unexplained galactosaemia. (No variants in GALT, GALK1, and GALE). This is therefore type IV galactosaemia. In vitro expression analysis and enzyme activity assay of the patients’ peripheral blood mononuclear cells showed total lack of or compromised expression of GALM protein. Loss-of-function mechanism. One homozygote for one of these variants p.(Gly142Arg) in gnomAD (African population). (Wada, Y. et al 2019; PMID: 30451973) In vitro expression assay and an enzyme activity assay of 67 GALM variants, taken from ExAc database (missense, nonsense, frameshift and splice). 30 variants concluded to be pathogenic due to no protein expression or faint expression. 5 variants with mildly lower levels were determined as likely pathogenic. All concluded to be loss-of-function mechanism. Incidence of galactosaemia by GALM deficiency is comparable to that of other galactosaemias. Carrier frequency and incidence was estimated for different populations. (Iwasawa, S. et al. (2019); PMID: 30910422)
Note only two of the reported individuals had cataracts.
Sources: Expert list
Created: 8 Jul 2020, 7:48 a.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
type IV galactosaemia
Tag watchlist tag was added to gene: GALM.
Gene: galm has been classified as Amber List (Moderate Evidence).
Phenotypes for gene: GALM were changed from type IV galactosaemia to Galactosemia IV, 618881
gene: GALM was added gene: GALM was added to Cataracts. Sources: Expert list Mode of inheritance for gene: GALM was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: GALM were set to 30451973; 30910422 Phenotypes for gene: GALM were set to type IV galactosaemia Review for gene: GALM was set to AMBER