Congenital myopathy

Gene: TRIM32

Red List (low evidence)

Comment on list classification: There are numerous patients reported with biallelic TRIM32 variants and LGMD / myopathy features. However, the age of onset is usually in 20s-30s, with few cases of childhood onset. This is not in scope of the congenital myopathy panel. TRIM32 is already Green on the LGMD panel. Hence, it should remain Red on Congenital myopathy.

Created: 17 Jun 2026, 10:36 a.m. | Last Modified: 17 Jun 2026, 10:36 a.m.

Panel Version: 7.62

PMID: 17994549 Saccone et al., 2008
Proband 1 - 44yo Croatian woman with slowly progressive proximal muscle weakness and respiratory weakness (onset around 37 yrs), homozygous for TRIM32: c.1560del (p.Cys521fs) - rare in gnomAD v4.1.1, 4 hets reported
Proband 3 - man from Southern Italy with weakness and paresthesia (onset in 30s); muscle biopsy at age 59 yrs showed muscular dystrophy, diagnosed with LGMD; lost the ability to walk at age 64 yrs, with scapular winging and marked atrophy in the limbs; homozygous for TRIM32 c.1181G>A, p.Arg394His - rare in gnomAD, 36 hets reported
Proband 4 - 15yo boy with elevated CK and muscle cramps after exercise, but no muscle weakness; heterozygous for TRIM32: c.1762_1764del, p.Asp588del - 2 hets in gnomAD v4.1.1.

PMID: 30823891 Servián-Morilla et al., 2019
Report of three independent families of Spanish and Australian origin with a muscular dystrophy, with biallelic TRIM32 mutations:
Family A: affected members homozygous for TRIM32 c.1771G > A (p.V591 M) - onset in teenage years with foot drop, with no other symptoms until 3rd decade
Family B: affected members were comp het for TRIM32 c.650 A > G (p.N217S) and c.1701_1703del (p.F568del) - onset of weakness in 20s
Family C: homozygous TRIM32 c.115_116insT (p.C39LfsX17) mutation seen in affected members - onset of muscle weakness in 3rd / 4th decade of life
Segregation studies showed that available healthy family members were WT or heterozygous for TRIM32 variants.

PMID: 37217920 Guan et al., 2023
Proband II1 - Chinese woman, 30yo, presented with fatigue and muscle weakness during pregnancy - diagnosed with LGMD; onset around 24yrs; muscle biopsy showed myopathic features; compound het for TRIM32 variant c.1700A > G, p.H567R & 43 kb deletion (results in removal of whole TRIM32 as well as a portion of ASTN2 gene - not linked to disease in OMIM; Method: WGS + Sanger; parents healthy het

PMID: 40017290 Caputo & Schoser, 2024 - case follow up for PMID: 15786463
Case 1 - boy with muscle weakness and pain after exercise, first noted at 6yrs; the weakness was progressive, and he was wheelchair bound at age 38yrs, respiratory insufficiency was present at age 44yrs; homozygous for TRIM32 p.D487N variant
Case 2 - younger brother of Case 1, first presented at 32 years with exercise induced muscle pain; progressive muscle weakness led to wheelchair use, respiratory symptoms noted at age 52yrs; elevated CK; homozygous for TRIM32 p.D487N variant

TRIM32 is associated with Muscular dystrophy, limb-girdle, autosomal recessive 8, OMIM:254110 (also Definitive in ClinGen, 2024), and AR ?Bardet-Biedl syndrome 11, OMIM:615988 (Limited in ClinGen, 2024) - resources accessed 17th June 2026.

Created: 17 Jun 2026, 10:29 a.m. | Last Modified: 17 Jun 2026, 10:38 a.m.

Panel Version: 7.63

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Muscular dystrophy, limb-girdle, autosomal recessive 8, OMIM:254110; autosomal recessive limb-girdle muscular dystrophy type 2H, MONDO:0009683

Publications

• 17994549
• 30823891
• 37217920
• 40017290

I don't know

recessive variants cause LGMD, disease onset can be in early age with increase CK and excerise intolerance. This gene is in the LGMD panel

Created: 27 May 2026, 9:42 a.m. | Last Modified: 27 May 2026, 9:42 a.m.

Panel Version: 7.25

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal