Severe microcephalyGene: SMG8
Comment on list classification: Rating Amber but can be promoted to Green at the next GMS panel update (added 'for-review' tag).
At least 5 unrelated families with microcephaly and different homozygous variants in the SMG8 gene. OFC recorded for only 3 families, but each includes at least one microcephalic individual with severity relevant to this panel (more than -3 SD)
Created: 23 Dec 2020, 5:13 p.m. | Last Modified: 23 Dec 2020, 5:13 p.m.
Panel Version: 2.56
Currently not associated with any phenotype in OMIM or G2P.
- PMID: 31130284 (2019) - Two individuals with distinct homozygous variants in this gene identified as part of a large candidate gene discovery study. Phenotype in one patient included microcephaly, ID, cataract, and neck hyperpigmentation; while the other presented short stature, microcephaly, fine motor delay, ventricular septal defect, failure to thrive, and facial dysmorphism.
- PMID: 33242396 (2020) - 9 affected individuals from 4 consanguineous families with different biallelic variants in the SMG8 gene. Clinical features include GDD/ID (8/8), dysmorphic features (9/9) microcephaly (6/9), short stature (4/9), brain imaging anomalies (4/5), congenital heart disease (3/9) and cataract (3/8). Some supportive functional data also provided. Microcephaly was recorded in 3/4 families, ranging in severity from -2.5 SD to -4.1 SD.
Created: 23 Dec 2020, 5:08 p.m.
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Intellectual disability; Microcephaly; Short stature; Facial dysmorphism
Gene: smg8 has been classified as Amber List (Moderate Evidence).
gene: SMG8 was added gene: SMG8 was added to Severe microcephaly. Sources: Literature for-review tags were added to gene: SMG8. Mode of inheritance for gene: SMG8 was set to BIALLELIC, autosomal or pseudoautosomal Publications for gene: SMG8 were set to 31130284; 33242396 Phenotypes for gene: SMG8 were set to Intellectual disability; Microcephaly; Short stature; Facial dysmorphism Review for gene: SMG8 was set to GREEN