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Gene: GLB1

Green List (high evidence)

GM1-gangliosidosis
Well established gene disease associaton.
The phenotypic spectrum of GM1 gangliosidosis is classified based on age of onset: Type I (infantile - <12 months age), Type II (late-infantile and juvenile) and Type III (adult). The clinical manifestations are variable and may include intellectual disability, cerebral degeneration, developmental delay, gait disturbance, kyphosis, scoliosis, joint stiffness, hepatomegaly, splenomegaly, facial dysmorphism and/or short stature. Functional studies are present and animal models.
Disease severity reported to be correlated with residual enzyme activity - <2% Infantile, ~2.65-3.05% (Juvenile), 4.24-7.28% (adult), with distinct pathogenic variant profiles. Reported variants in population that cause reduction in enzymatic activity, but not to the level of an individual displaying phenotype (PMID: 32219518).

Mucopolysaccharidosis type IVB (Morquio)
Falls within the spectrum of GLB1-related disorders, but unlike GM1 gangliosidosis, the disease is less severe, with primarily skeletal features, corneal clouding, but absence of neurological features including intellectual disability.
Functional studies are present and animal models. Onset commonly reported in childhood. Trp273Leu is most common variant (likely founder).

Created: 31 Oct 2024, 12:09 a.m. | Last Modified: 31 Oct 2024, 12:09 a.m.

Panel Version: 1.521

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
GM1-gangliosidosis, type I MIM#230500; GM1-gangliosidosis, type II MIM#230600; GM1-gangliosidosis, type III MIM#230650; Mucopolysaccharidosis type IVB (Morquio) MIM#253010

Publications

• 34539759 24156116 16941474 17309651 25936995 32219518 1928092 33558080 10841810