Congenital muscular dystrophy and congenital myopathy

Gene: BIN1

Comment on mode of inheritance: Only one case with monoallelic BIN1 variant has been reported with childhood-onset myopathy. As there are not sufficient cases, the MOI should remain as "BIALLELIC, autosomal or pseudoautosomal" for now. "watchlist_moi" tag has been added to review the MOI when new evidence becomes available.

Created: 22 Dec 2023, 10:18 a.m. | Last Modified: 22 Dec 2023, 10:18 a.m.

Panel Version: 0.208

PMID:29103045 reported a Dutch family with monoallelic variant in BIN1 gene (c.53T>A (p.Val18Glu)). The main features were mild proximal weakness with pronounced myalgia, exercise intolerance and large muscle mass, with a childhood onset in the youngest generation and mild cognitive features.

However, PMID:25260562 and PMID:27854204 reported patients with monoallelic variants presenting with mild and adult-onset centronuclear myopathy with myalgia and CK elevation.

Disease caused only by biallelic inheritance (and not by monoallelic inheritance) has currently been reported in OMIM and Gene2Phenotype.

Created: 22 Dec 2023, 10:16 a.m. | Last Modified: 22 Dec 2023, 10:16 a.m.

Panel Version: 0.206

Anna Sarkozy (Great Ormond Street Hospital) editing her previous review on this gene on the old GMS Congenital myopathy panel on 24 Mar 2023 notes (rated Green): 'Adult-onset autosomal dominant centronuclear myopathy, also with myalgia and CK elevation'.

Mode of inheritance: BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes: Centronuclear Myopathy, Recessive; Myopathy, centronuclear, autosomal recessive, 255200; dominant centronuclear myopathy

Publications: PMID: 25260562; 27854204

Created: 22 Dec 2023, 10:16 a.m. | Last Modified: 22 Dec 2023, 10:20 a.m.

Panel Version: 0.208

Publications

• 29103045

I don't know

Gene rating and review submitted by Rachael Mein, Viapath Guy's Hospital February 2019 on on behalf of London South GLH for the GMS Neurology specialist test group.

Created: 30 Apr 2019, 10:09 a.m.

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Centronuclear Myopathy, Recessive; Myopathy, centronuclear, autosomal recessive, 255200

Publications

• 17676042

Green List (high evidence)

Mode of inheritance
BIALLELIC, autosomal or pseudoautosomal

Phenotypes
Centronuclear Myopathy, Recessive; Myopathy, centronuclear, autosomal recessive, 255200

Green List (high evidence)

Comment when marking as ready: Biallelic cases reported with appropriate phenotype for inclusion.

Created: 2 Feb 2017, 11:03 a.m.

Comment on mode of inheritance: This is appropriate for the birth - childhood onset cases. AD inheritance reported but mild and adult onset. Therefore biallelic MOI is appropriate.

Created: 2 Feb 2017, 11:02 a.m.

4 separate families with homozygous mutations found in association with the phenotype via OMIM.

I have included monoallelic inheritance in the MOI in view of 2016 case report of AD inheritance (PMID 27854204) and also cases from 2014 (PMID 25260562). The latter includes 5 families with 9 cases in whom heterozygous mutations were identified. However, OMIM only has AR inheritance listed.

Created: 23 Jan 2017, 4:55 p.m.

Mode of inheritance
BOTH monoallelic and biallelic, autosomal or pseudoautosomal

Phenotypes
Myopathy, centronuclear, autosomal recessive 255200

Publications

• PMID: 27854204
• 25260562