Congenital myopathy
Gene: HMGCS1EnsemblGeneIds (GRCh38): ENSG00000112972
EnsemblGeneIds (GRCh37): ENSG00000112972
OMIM: 142940, Gene2Phenotype
HMGCS1 is in 2 panels
2 reviews
Achchuthan Shanmugasundram (Genomics England Curator)
Comment on list classification: As reviewed by Anna Sarkozy, there is sufficient evidence available (four unrelated families and functional evidence) for the association of biallelic HMGCS1 variants with congenital myopathy. Hence, this gene can be promoted to green rating in the next GMS update.Created: 27 May 2026, 8:09 p.m. | Last Modified: 27 May 2026, 8:09 p.m.
Panel Version: 7.31
PMID:39531736 (2025) reported biallelic variants in HMGCS1 gene identified via whole exome and genome sequencing in five patients from four unrelated families with rigid spine syndrome. The identified variants included 6 missense variants and one 2-basepair deletion resulting in a frameshift and early termination. All patients presented with spinal rigidity primarily affecting the cervical and dorsolumbar regions, scoliosis, and respiratory insufficiency. Creatine kinase levels were variably elevated and muscle biopsies revealed irregularities in oxidative enzyme staining with occasional internal nuclei and rimmed vacuoles.
Three of the four functionally analysed variants exhibited reduced thermal stability, and two of them showed subtle changes in enzymatic activity compared to the wildtype. Hmgcs1 mutant zebrafish displayed severe early defects and the four variants tested have reduced function compared to wild-type HMGCS1 in zebrafish rescue assays. In addition, potential for mevalonic acid supplementation to reduce phenotypic severity in mutant zebrafish was also demonstrated.
This gene has been associated with relevant phenotype in OMIM (MIM #62143) and the OMIM record was last accessed on 27 May 2026.Created: 27 May 2026, 8:07 p.m. | Last Modified: 27 May 2026, 8:07 p.m.
Panel Version: 7.28
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Phenotypes
Congenital myopathy 28 with rigid spine, OMIM:621433; congenital myopathy 28 with rigid spine, MONDO:0980756
Publications
Anna Sarkozy (Great Ormond Street Hospital)
novel form of CM with rigid spine, reported in a few families from Spain and JapanCreated: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.
Panel Version: 7.14
Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal
Publications
Details
- Mode of Inheritance
- BIALLELIC, autosomal or pseudoautosomal
- Sources
-
- Expert Review Amber
- NHS GMS
- Phenotypes
-
- Congenital myopathy 28 with rigid spine, OMIM:621433
- congenital myopathy 28 with rigid spine, MONDO:0980756
- Tags
- OMIM
- 142940
- Clinvar variants
- Variants in HMGCS1
- Penetrance
- None
- Publications
- Panels with this gene
History Filter Activity
Entity classified by Genomics England curator
Achchuthan Shanmugasundram (Genomics England Curator)Gene: hmgcs1 has been classified as Amber List (Moderate Evidence).
Added Tag, Added Tag
Achchuthan Shanmugasundram (Genomics England Curator)Tag Q2_26_promote_green tag was added to gene: HMGCS1. Tag Q2_26_NHS_review tag was added to gene: HMGCS1.
Set Phenotypes
Achchuthan Shanmugasundram (Genomics England Curator)Phenotypes for gene: HMGCS1 were changed from to Congenital myopathy 28 with rigid spine, OMIM:621433; congenital myopathy 28 with rigid spine, MONDO:0980756
Set publications
Achchuthan Shanmugasundram (Genomics England Curator)Publications for gene: HMGCS1 were set to
Entity classified by Genomics England curator
Arina Puzriakova (Genomics England Curator)Gene: hmgcs1 has been removed from the panel.
Created, Added New Source, Set mode of inheritance
Arina Puzriakova (Genomics England Curator)gene: HMGCS1 was added gene: HMGCS1 was added to Congenital myopathy. Sources: NHS GMS Mode of inheritance for gene: HMGCS1 was set to BIALLELIC, autosomal or pseudoautosomal