Ataxia and cerebellar anomalies - narrow panel

Gene: LSM7

Comment on list classification: Rating Amber as one individual died in utero and their phenotype could not be compared to the other two cases. Additionally, although likely homozygous based on the carrier status of the parents, the genotype of this individual is presumed and not confirmed. Overall the evidence is borderline Amber/Green so adding a watchlist tag to monitor for additional studies.

Created: 12 Mar 2025, 3:05 p.m. | Last Modified: 12 Mar 2025, 3:05 p.m.

Panel Version: 6.9

Additional family identified with compound heterozygous missense variants in this gene (PMID:39420558). The proband presented with neurodevelopmental defects, leukodystrophy, spastic quadriparesis, and cerebellar atrophy. Authors state that this individual harboured heterozygous variants of each of the previously reported homozygous variants identified in patients from PMID:35047835.

Created: 12 Mar 2025, 2:58 p.m. | Last Modified: 12 Mar 2025, 2:58 p.m.

Panel Version: 6.8

Comment on publications: PMID: 39420558 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: 12 Mar 2025, 2:43 p.m. | Last Modified: 12 Mar 2025, 2:43 p.m.

Panel Version: 6.8

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 35047835
• 39420558

Comment on list classification: New gene added by Zornitza Stark (Australian Genomics). This gene is not associated with a phenotype in OMIM or Gene2Phenotype. Currently there is not enough evidence to support a gene-disease association. Until there are more cases this gene has been given a Red rating.

Created: 19 May 2021, 9:16 a.m. | Last Modified: 19 May 2021, 9:16 a.m.

Panel Version: 1.96

Red List (low evidence)

Homozygous variant (p.Asp41Asn) identified in a child with leukodystrophy and a homozygous variant (p.Arg69Pro) identified in an individual that died in utero. In vitro and in vivo (zebrafish) assays supporting pathogenicity of the 2 variants.
Sources: Literature

Created: 10 May 2021, 10:29 a.m.

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Leukodystrophy; fetal death

Publications

• https://doi.org/10.1016/j.xhgg.2021.100034