Limb girdle muscular dystrophies, myofibrillar myopathies and distal myopathies

Gene: PABPN1

Green List (high evidence)

Comment on list classification: There are at least 3 unrelated individuals reported in literature with heterozygous point mutations in PABPN1 and Oculopharyngeal muscular dystrophy. While the disease is most often caused by PABPN1 trinucleotide repeats, the recurrent heterozygous PABPN1 p.Gly12Ala mutation results in 13 contiguous alanine codons with the same pathogenic effect. Based on available evidence, this gene should be promoted to Green with MOI set to MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted.

Created: 16 Mar 2026, 5:04 p.m. | Last Modified: 16 Mar 2026, 5:09 p.m.

Panel Version: 5.31

PMID: 16648376 Robinson et al., 2006
Cohort of 202 patients with tentative diagnosis of Oculopharyngeal muscular dystrophy; only sequenced exon 1 of PABPN1. Reported a case with OPMD (patient A, female, European, disease onset around 61 years) negative for the repeat expansion, heterozygous for PABPN1 c.35G>C; p.Gly12Ala variant. There was a pattern of dominant inheritance in the family (not genotyped).

PMID: 21742497 Robinson et al., 2011
Report of 2 further cases with heterozygous PABPN1 c.35G>C; p.Gly12Ala and OPMD diagnosis.
Case 1 - male, bilateral ptosis and choking at 65 years old; no limb muscle weakness reported.
Case 2 - female, onset of swallowing difficulty around age 60, ptosis onset at age 65 years, muscle weakness reported in 70s. No vacuoles seen on deltoid muscle biopsy.

PMID: 34225694 Nishii et al., 2021
Report of a 78 yo woman with oculopharyngeal muscular dystrophy - presented with ptosis and gradually progressive dysphagia (symptom onset at 62 years). A physical examination and muscle imaging (MRI and ultrasound) showed impairment of the tongue, proximal muscles of the upper limbs, and flexor muscles of the lower limbs. EMG of bulbar and facial muscles revealed a myopathic pattern. Her son had the same symptoms (ptosis and dysphasia). Sequencing revealed PABPN1 c.35G > C; p.Gly12Ala point mutation.

PMID: 36847015 Takahashi et al., 2023
Case report - 77 yo male patient with heterozygous PABPN1 c.34G > T (p.Gly12Trp) mutation, no polyalanine expansion detected. He presented with slowly progressive bilateral ptosis, dysphagia, and symmetrical proximal dominant muscle weakness - disease onset around 60 yo. MRI revealed selective fat replacement of the tongue, bilateral adductor magnus, and soleus muscles. Muscle biopsy sample revealed PABPN1-positive aggregates in the myonuclei - reported to be specific to OPMD.

PABPN1 is linked to AD Oculopharyngeal muscular dystrophy, OMIM:164300 (OMIM accessed 16 Mar 2026).
Sources: Literature

Created: 16 Mar 2026, 4:57 p.m. | Last Modified: 16 Mar 2026, 5:17 p.m.

Panel Version: 5.31

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
Oculopharyngeal muscular dystrophy, OMIM:164300; oculopharyngeal muscular dystrophy, MONDO:0008116

Publications

• 16648376
• 21742497
• 34225694
• 36847015