Muscular dystrophy and myopathy_Paediatric
Gene: FHL1EnsemblGeneIds (GRCh38): ENSG00000022267
EnsemblGeneIds (GRCh37): ENSG00000022267
OMIM: 300163, Gene2Phenotype
FHL1 is in 12 panels
3 reviews
Bryony Thompson (Royal Melbourne Hospital)
Well-established gene-disease association. FHL1 encodes 3 alternatively spliced isoforms - FHL1A, FHL1B, FHL1C composed of different LIM domains. FHL1A is predominant in muscle. Pathogenic variants affected isoform expression differently depending on location in alternatively spliced exons. Location of the variant appears to be related to severity of phenotype. Loss of function is the mechanism of disease.
Reducing body myopathy (RBM) PMID: 18179901, 19716112, 18274675, 19181672, 25274776, 34366191 - XLD inheritance with clinical spectrum that includes severe early-onset to later-onset less progressive conditions including X-linked scapuloperoneal muscular dystrophy & X-linked myopathy with postural muscle atrophy. Pathogenic variants mainly located in more proximal exons (3-6). Fhl1 W122S knock-in mouse model has late-onset mild myopathy.
XL-EDMD PMID: 19716112, 20186852, 20301609 - at least 7 families reported with XLD inheritance (female heterozygous carriers were asymptomatic or had mild myopathy and/or cardiomyopathy). EDMD-associated variants are localized in the distal exons (5-8) and associated with reduced function.Created: 10 May 2022, 7:08 a.m. | Last Modified: 10 May 2022, 7:08 a.m.
Panel Version: 0.14039
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Reducing body myopathy MONDO:0019948; X-linked Emery-Dreifuss muscular dystrophy MONDO:0010680
Publications
Variants in this GENE are reported as part of current diagnostic practice
Elena Savva (Victorian Clinical Genetics Services)
XLD, severe progressive myopathy with onset in infancy.
PMID: 19181672 - 11 patients (9 families) with reducing body myopathy. All patients had progressive muscle weakness with 7/11 having onset <5 years old. Majority had proximal muscle weakness with elevated CK levels. Authors note "we would be hesitant to use the term dystrophic for this myopathy as the mechanisms of cell damage remain to be fully worked out"
p.His123 is a hotspot with recurring de novo missense mutations at this residue.
PMID: 19171836 - 5 patients with reducing body myopathy, 2/5 had fatal infantile forms of disease.
Summary: congenital onset has been found, however unsure if this qualifies as a dystrophy or only myopathy
Sources: Expert listCreated: 24 Jun 2020, 3:25 a.m.
Mode of inheritance
X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
Phenotypes
Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717
Publications
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)
XLD, severe progressive myopathy with onset in infancy.
Sources: Expert listCreated: 11 Jun 2020, 8:31 a.m.
Mode of inheritance
Other
Phenotypes
Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717
Publications
Details
- Mode of Inheritance
- X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males)
- Sources
-
- Expert Review Green
- Expert list
- Expert list
- Phenotypes
-
- Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717
- OMIM
- 300163
- Clinvar variants
- Variants in FHL1
- Penetrance
- None
- Publications
- Panels with this gene
-
- Mackenzie's Mission_Reproductive Carrier Screening
- Limb-Girdle Muscular Dystrophy and Distal Myopathy
- Additional findings_Paediatric
- Prepair 1000+
- Cardiomyopathy_Paediatric
- Arthrogryposis
- Mendeliome
- BabyScreen+ newborn screening
- Prepair 500+
- Transplant Co-Morbidity Superpanel
- Muscular dystrophy and myopathy_Paediatric
- Hypertrophic cardiomyopathy_HCM
History Filter Activity
Entity classified by Genomics England curator
Bryony Thompson (Royal Melbourne Hospital)Gene: fhl1 has been classified as Green List (High Evidence).
Set publications
Bryony Thompson (Royal Melbourne Hospital)Publications for gene: FHL1 were set to PMID: 19181672; 19171836
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Entity classified by Genomics England curator
Zornitza Stark (Victorian Clinical Genetics Services; Australian Genomics)Gene: fhl1 has been classified as Amber List (Moderate Evidence).
Created, Added New Source, Set mode of inheritance, Set publications, Set Phenotypes
Elena Savva (Victorian Clinical Genetics Services)gene: FHL1 was added gene: FHL1 was added to Muscular dystrophy. Sources: Expert list Mode of inheritance for gene: FHL1 was set to X-LINKED: hemizygous mutation in males, monoallelic mutations in females may cause disease (may be less severe, later onset than males) Publications for gene: FHL1 were set to PMID: 19181672; 19171836 Phenotypes for gene: FHL1 were set to Reducing body myopathy, X-linked 1a, severe, infantile or early childhood onset, MIM# 300717 Review for gene: FHL1 was set to AMBER