Congenital muscular dystrophy

Gene: HMGCR

Green List (high evidence)

Comment on list classification: At least 6 unrelated families have been reported with HMGCR-related limb-girdle muscular dystrophy. Age of onset is variable but has been reported as early as 4 months and therefore this gene can be promoted to Green at the next GMS panel update.

Created: 17 Jun 2026, 11:44 a.m. | Last Modified: 17 Jun 2026, 11:44 a.m.

Panel Version: 7.15

Yogev et al. 2023 (PMID:36745799) reported 6 affected individuals from a consanguineous Bedouin family who presented during the fourth decade of life with muscle pain and progressive muscle fatigue and weakness, mainly affecting the proximal and axial muscles. Only mild atrophy of affected muscles was noted. None suffered from any other neurological deficits or dysphagia. Genome-wide linkage analysis of eight family members, identified a single 3.2 Mbp homozygous segment (5q13.2-q13.3), that was shared among all affected individuals and was either absent or heterozygous in unaffected individuals. WES in two affected individuals revealed a single missense variant within the 3.2Mbp locus, c.2465G>A; p.(G822D) in the HMGCR gene. In vitro functional studies of the variant supported a partial loss of function effect.

Morales-Rosado et al. 2023 (PMID:37167966) reported 9 patients from 5 unrelated families with with unexplained limb-girdle like muscular dystrophy and biallelic variants in HMGCR. Age at symptom recognition ranged from 4 months to 10 years. Symptoms included hypotonia, delayed motor milestones, and axial and neck muscle weakness. Progressive proximal muscle weakness of the upper and lower limbs, waddling gait, muscle atrophy, and increased serum creatine kinase were also described. Muscle biopsies in most affected individuals showed non-specific dystrophic changes with non-diagnostic immunohistochemistry. Biallelic pathogenic variants identified by exome sequencing including missense, in-frame deletion and splice site. Protein activity studies using three missense variants confirmed decreased enzymatic activity and reduced protein stability.

Created: 17 Jun 2026, 11:35 a.m. | Last Modified: 17 Jun 2026, 11:35 a.m.

Panel Version: 7.12

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 28, OMIM:620375

Publications

• 37167966
• 36745799

Green List (high evidence)

causes a recessive form of muscular dystrophy, green in LGMD, but given the overlap and relative early onset I would add for CMD panel

Created: 22 May 2026, 1:49 p.m. | Last Modified: 22 May 2026, 1:49 p.m.

Panel Version: 7.6

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Publications

• 37167966
• 36745799