Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: PABPN1

Included for overlapping phenotype
Sources: Other

Created: 14 Apr 2023, 7:05 a.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
oculopharyngeal muscular dystrophy MONDO:0008116

Publications

• 19080757
• 33805441
• 16648376

Green List (high evidence)

Oculopharyngeal muscular dystrophy (OPMD) is a late-onset muscle disease (usually 5th or 6th decade of life) associated with progressive ptosis of the eyelids, dysphagia, and unique tubulofilamentous intranuclear inclusions (INIs) in skeletal muscle. It is most commonly an autosomal dominant condition but rarely recessive inheritance has been reported. It is caused by the abnormal expansion of the alanine-encoding (GCN)n trinucleotide repeat in the N-terminal domain of the gene (11–18 repeats in OPMD instead of the normal 10 repeats).

A coding triplet repeat usually causes this condition, which is not detectable using WES. However, a missense substitution, Gly12Aal occurs immediately 3-prime to the normal 10 alanine codon repeat sequence and generates a contiguous sequence of 13 alanine codons, which is causative of disease in the common triplet repeat expansion mutation.

NM_004643.3:c.4_6[X]
Expected gain of function mechanism of disease
Normal allele: (GCN)10 / Ala10
Autosomal recessive: (GCN)11/Ala11
Autosomal dominant: (GCN)12-17

Created: 29 Mar 2022, 11:47 p.m. | Last Modified: 29 Mar 2022, 11:47 p.m.

Panel Version: 0.12282

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Oculopharyngeal muscular dystrophy - MIM#164300

Publications

• 19080757
• 33805441