Limb-Girdle Muscular Dystrophy and Distal Myopathy

Gene: PABPN1

Green List (high evidence)

PABPN1 (poly(A) binding protein nuclear 1)
EnsemblGeneIds (GRCh38): ENSG00000100836
EnsemblGeneIds (GRCh37): ENSG00000100836
OMIM: 602279, Gene2Phenotype
PABPN1 is in 5 panels

2 reviews

Bryony Thompson (Royal Melbourne Hospital)

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

Krithika Murali (Victorian Clinical Genetics Services)

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

Details

Mode of Inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal
Sources
  • Expert Review Green
  • Other
Phenotypes
  • oculopharyngeal muscular dystrophy MONDO:0008116
OMIM
602279
Clinvar variants
Variants in PABPN1
Penetrance
None
Publications
Panels with this gene

History Filter Activity

17 Apr 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: pabpn1 has been classified as Green List (High Evidence).

17 Apr 2023, Gel status: 3

Entity classified by Genomics England curator

Bryony Thompson (Royal Melbourne Hospital)

Gene: pabpn1 has been classified as Green List (High Evidence).

14 Apr 2023, Gel status: 1

Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes

Bryony Thompson (Royal Melbourne Hospital)

gene: PABPN1 was added gene: PABPN1 was added to Limb-Girdle Muscular Dystrophy and Distal Myopathy. Sources: Other Mode of inheritance for gene: PABPN1 was set to BOTH monoallelic and biallelic, autosomal or pseudoautosomal Publications for gene: PABPN1 were set to 19080757; 33805441; 16648376 Phenotypes for gene: PABPN1 were set to oculopharyngeal muscular dystrophy MONDO:0008116