Severe microcephaly

Gene: PNPLA8

Green List (high evidence)

Comment on publications: PMID: 39082157 was identified by the Genomics England Applied Machine Learning (ML) team in a Biocuration-ML project for identifying new gene-disease associations using Natural Language Processing (NLP) and Generative AI techniques.

Created: 26 Feb 2025, 5:08 p.m. | Last Modified: 26 Feb 2025, 5:08 p.m.

Panel Version: 7.15

Biallelic PNPLA8 variants have previously been associated with Mitochondrial myopathy with lactic acidosis, (OMIM:251950). PMID: 39082157 reports a study were microcephaly, global delay and seizures are associated with biallelic PNPLA8 variants. Amongst the unrelated individuals studied, 8/11 had severe microcephaly, 9/11 had epileptic seizures and 8/11 had severe global delay and intellectual disability where it could be measured, 3/11 cases died in childhood and affected siblings (but not genotyped) had died in two other families. Using cerebral organoids generated from human induced pluripotent stem cells, the authors were able to assert that the loss of PNPLA8 led to
developmental defects by reducing the number of basal radial glial cells and upper-layer neurons (PMID: 39082157).
Sources: Literature

Created: 26 Feb 2025, 5:03 p.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
?Mitochondrial myopathy with lactic acidosis, OMIM:251950; mitochondrial myopathy-lactic acidosis-deafness syndrome MONDO:0016825

Publications

• 39082157