Congenital muscular dystrophy

Gene: HNRNPA2B1

Green List (high evidence)

The rating of this gene has been updated to green following NHS Genomic Medicine Service approval.

Created: 1 Feb 2023, 4:51 p.m. | Last Modified: 1 Feb 2023, 4:51 p.m.

Panel Version: 3.22

Green List (high evidence)

Comment on list classification: There is enough evidence for this gene to be rated GREEN at the next major review.

Created: 15 Dec 2022, 12:02 p.m. | Last Modified: 15 Dec 2022, 12:02 p.m.

Panel Version: 3.11

Comment on phenotypes: The OMIM phenotype for HNRNPA2B1 (?Inclusion body myopathy with early-onset Paget disease with or without frontotemporal dementia 2, OMIM:615422) is based on one family. PMID: 35484142 presents further variants associated with an expanded phenotype.

Created: 15 Dec 2022, 12:01 p.m. | Last Modified: 15 Dec 2022, 12:01 p.m.

Panel Version: 3.10

PMID: 35484142 reports nine heterozygous terminating HNRNPA2B1 variants in ten unrelated cases of early onset severe, progressive muscular dystrophy, reminiscent of oculopharyngeal muscular dystrophy (OPMD)

Created: 15 Dec 2022, 11:57 a.m. | Last Modified: 15 Dec 2022, 11:57 a.m.

Panel Version: 3.9

The Q1_22_rating tag has been added as the GMS review for this gene has not been received to date

Created: 3 Feb 2022, 4:16 p.m. | Last Modified: 3 Feb 2022, 4:16 p.m.

Panel Version: 2.21

Comment on list classification: De novo terminating variants clustered in the C-terminus of the protein have been reported in six unrelated families all with a distinct class of dominantly-acting heterozygous variants in hnRNPA2B1 with a unique clinical phenotype of early childhood-onset progressive muscle weakness, ophthalmoplegia, ptosis, dysphagia, and variable degrees of respiratory insufficiency but no dementia (https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext)
This source is a meeting abstract an there is no peer reviewed source at this time.

There is enough evidence for this gene to be green, but GMS opinion is required to confirm this.

Created: 12 Jan 2021, 3:02 p.m. | Last Modified: 28 Jan 2021, 5:54 p.m.

Panel Version: 2.5

Phenotypes
early-onset oculopharyngeal muscular dystrophy

Publications

• 35484142

Green List (high evidence)

ten independent families reported with a severe, progressive muscular dystrophy with early onset, and de novo frameshift variants in this gene. phenotype is caractherised by symptoms onset before 2 years of age with severe respiratory insufficiency, delayed motor milestones, ptosis and ophthalmoplegia, axial weakness, progressive proximal and distal weakness. Creatine kinase levels were elevated. Disease-causing frameshift mutations abolish the native stop codon and extend the reading frame, creating novel transcripts that escape nonsense-mediated decay and alter the nucleocytoplasmic transport dynamics. in view of this evidence this gene should be upgraded to green

Created: 10 Nov 2022, 12:35 p.m. | Last Modified: 10 Nov 2022, 12:35 p.m.

Panel Version: 2.31

de novo variants in this gene have been reported in multiple unrelated families and presented at the World muscle society congress 2020, a full publication is currently in progress. see abstract:
https://www.nmd-journal.com/article/S0960-8966(20)30203-0/fulltext
Sources: Other, Expert list, Research

Created: 8 Dec 2020, 2:21 p.m.

Mode of inheritance
MONOALLELIC, autosomal or pseudoautosomal, NOT imprinted

Phenotypes
early-onset oculopharyngeal muscular dystrophy, muscular dystrophy, congenital myopathy

Publications

• 35484142