Severe microcephaly

Gene: SMG8

The rating of this gene has been updated following NHS Genomic Medicine Service approval.

Created: 10 Mar 2022, 10:52 a.m. | Last Modified: 10 Mar 2022, 10:52 a.m.

Panel Version: 2.282

Green List (high evidence)

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.
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- 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.
Sources: Literature

Created: 23 Dec 2020, 5:08 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Intellectual disability; Microcephaly; Short stature; Facial dysmorphism

Publications

• 31130284
• 33242396