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FHL1-Myopathies via the FHL1 Gene

Summary and Pricing

Test Method

Exome Sequencing with CNV Detection
Test Code Test Copy GenesTest CPT Code Gene CPT Codes Copy CPT Codes Base Price
FHL1 81404 81404,81479 $990
Test Code Test Copy Genes Test CPT Code Gene CPT Codes Copy CPT Code Base Price
8553FHL181404 81404,81479 $990 Order Options and Pricing

Pricing Comments

Our favored testing approach is exome based NextGen sequencing with CNV analysis. This will allow cost effective reflexing to PGxome or other exome based tests. However, if full gene Sanger sequencing is desired for STAT turnaround time, insurance, or other reasons, please see link below for Test Code, pricing, and turnaround time information.

An additional 25% charge will be applied to STAT orders. STAT orders are prioritized throughout the testing process.

Click here for costs to reflex to whole PGxome (if original test is on PGxome Sequencing platform).

Click here for costs to reflex to whole PGnome (if original test is on PGnome Sequencing platform).

The Sanger Sequencing method for this test is NY State approved.

For Sanger Sequencing click here.

Turnaround Time

3 weeks on average for standard orders or 2 weeks on average for STAT orders.

Please note: Once the testing process begins, an Estimated Report Date (ERD) range will be displayed in the portal. This is the most accurate prediction of when your report will be complete and may differ from the average TAT published on our website. About 85% of our tests will be reported within or before the ERD range. We will notify you of significant delays or holds which will impact the ERD. Learn more about turnaround times here.

Targeted Testing

For ordering sequencing of targeted known variants, go to our Targeted Variants page.


Genetic Counselors


  • Angela Gruber, PhD

Clinical Features and Genetics

Clinical Features

Disorders of skeletal muscle resulting from mutations in the FHL1 gene vary by age of onset, rate of progression, severity of clinical presentation, and findings from muscle histopathology. Severe, early onset reducing body myopathy (OMIM 300717) is characterized by early onset and progressive hypotonia, proximal muscle weakness, contractures, and respiratory insufficiency. Patients are normal at birth until they develop proximal weakness as toddlers (Kiyomoto et al. J Neurol Sci 128:58-65, 1995; Schessl et al. Brain 132:452-464, 2009). In the reported patients, disease progression was rapid and respiratory failure occurred 2-3 years after disease onset. Initial clinical signs included frequent falls, abnormal gait, progressive proximal muscle weakness, contractures, and scoliosis. Childhood onset reducing body myopathy (OMIM 300718) exhibits onset between 5 and 16 years of age. Disease progression is also rapid with patients becoming wheelchair bound one and three years from the time of onset (Goebel et al. Neuropediatrics 32:196-205, 2001; Schessl et al. J Clin Invest 118:904-912, 2008). Clinical features include proximal weakness, joint contractures, spinal rigidity, scoliosis, scapular winging, Gowers sign, and decreased deep tendon reflexes (Ohsawa et al. Brain Dev 29:112-116, 2007, Liewluck et al. Muscle Nerve 35:322-326, 2007). Mothers of affected boys have milder symptoms later in life compared to their children.

X linked myopathy with postural muscle atrophy (OMIM 300696) is an adult onset disorder with weakness and atrophy of muscles required for postural stability. Patients often exhibit muscle hypertrophy early in life and in non proximal muscle groups. Among a group of seven unrelated families, disease onset was between 8 and 45 years of age and women carriers were either asymptomatic or mildly affected (Schoser et al. Neurology 73:543-551, 2009). Patients in this study had early-onset neck rigidity, contractures of the Achilles tendon, progressive limb girdle muscle weakness, postural muscle atrophy, rigid spine, scapular winging, gait abnormalities, and respiratory insufficiency.

Emery-Dreifuss muscular dystrophy-6 (OMIM 300696) is a closely related clinical phenotype to that of X linked myopathy with postural muscle atrophy. Age at onset has been found to be in the first to second decades of life in two studies (Gueneau et al. Am J Hum Genet 85:338-353, 2009; Knoblauch et al. Ann Neurol 67:136-140, 2010). Patients develop cardiac muscle involvement, including arrhythmias and hypertrophic cardiomyopathy, after onset of skeletal muscle symptoms. Clinical features include joint contractures, neck stiffness, and limb girdle muscle weakness and atrophy.

All patients reported have remained ambulatory. Female carriers are rarely affected (Gueneau et al. Am J Hum Genet 85: 338-353, 2009). Scapuloperoneal myopathy (OMIM 300695) has been described in a single family (Wilhelmsen et al. Ann Neurol 39:507-520, 1996). Clinical features include foot drop, proximal arm weakness which precedes hand weakness, and scapular winging. Affected men showed signs earlier in life than women and were more severely affected (Quinzii et al. Am J Hum Genet 82:208-213, 2008).

Patients with myofibrilar myopathy with reducing bodies seen in muscle biopsies have also been found with FHL1 gene mutations (Selcen et al. Neurology 77:1951, 2011).

Reducing bodies are irregularly shaped cytoplasmic inclusions that appear dark with menadione-NBT stain, confirming the presence of sulfhydryl groups. FHL1 protein, both mutant and normal forms, is the most abundant protein found in reducing bodies (Schessl et al. J Clin Invest 118:904–912, 2008; Schessl et al. Brain 132:452-464, 2009). Muscle biopsies of patients with FHL1 myopathies reveal variation in fiber size, internally placed nuclei, mild inflammation, rimmed vacuoles, and reducing bodies that stain with NBT.


FHL1-related myopathies are inherited as X-linked recessive disorders or, in the case of scapuloperoneal myopathy, as an X-linked dominant disorder. In familial cases, mothers of affected males are themselves clinically less affected with symptoms appearing later in life. Severe, early onset reducing body myopathy results from de novo missense mutation of conserved amino acids of the second LIM domain (Schessl et al. J Clin Invest 118:904-912, 2008; Shalaby et al. Neurology 72:375-376, 2009). Mutations involving the zinc coordinating residue p.His123 result in a severe clinical course, while mutations in another zinc coordinating residue (p.Cys153) are associated with a milder phenotype. Childhood onset reducing body myopathy results from inherited mutations of the second LIM domain. The scapuloperoneal myopathy mutation is found in the second LIM domain and affects a conserved residue (p.Trp122Ser). Patients with Emery-Dreifuss muscular dystrophy-6 more often have FHL1 mutations in the fourth LIM domain. The majority of reported mutations in FHL1 are missense or nonsense (Human Gene Mutation Database).

Clinical Sensitivity - Sequencing with CNV PGxome

Analytical sensitivity should be high because nearly all FHL1 mutations reported to date are detectable by direct sequencing of genomic DNA.

Testing Strategy

This test provides full coverage of all coding exons of the FHL1 gene plus 10 bases of flanking noncoding DNA in all available transcripts along with other non-coding regions in which pathogenic variants have been identified at PreventionGenetics or reported elsewhere. We define full coverage as >20X NGS reads or Sanger sequencing. PGnome panels typically provide slightly increased coverage over the PGxome equivalent. PGnome sequencing panels have the added benefit of additional analysis and reporting of deep intronic regions (where applicable).

Dependent on the sequencing backbone selected for this testing, discounted reflex testing to any other similar backbone-based test is available (i.e., PGxome panel to whole PGxome; PGnome panel to whole PGnome).

Indications for Test

Patients with clinical and histopathological features of FHL1-related disorders.


Official Gene Symbol OMIM ID
FHL1 300163
Inheritance Abbreviation
Autosomal Dominant AD
Autosomal Recessive AR
X-Linked XL
Mitochondrial MT

Related Test

Comprehensive Cardiology Panel


  • Goebel, H. H., et al. (2001) Reducing body myopathy with cytoplasmic bodies and rigid spine syndrome: a mixed congenital myopathy. Neuropediatrics 32: 196-205.  PubMed ID: 11571700
  • Gueneau, L., et al. (2009) Mutations of the FHL1 gene cause Emery-Dreifuss muscular dystrophy. Am. J. Hum. Genet. 85: 338-353.  PubMed ID: 19716112
  • Human Gene Mutation Database.
  • Kiyomoto, B. H., et al. (1995) Fatal reducing body myopathy: ultrastructural and immnunohistochemical (sic) observations. J. Neurol. Sci. 128: 58-65.  PubMed ID: 7722535
  • Knoblauch, H. et al. (2010) Contractures and hypertrophic cardiomyopathy in a novel FHL1 mutation. Ann. Neurol. 67: 136-140. PubMed ID: 20186852
  • Liewluck, T. et al. (2007)  Unfolded protein response and aggresome formation in hereditary reducing-body myopathy. Muscle Nerve 35: 322-326. PubMed ID: 17099882
  • Ohsawa, M. et al. (2007)  Familial reducing body myopathy. Brain Dev. 29: 112-116.  PubMed ID: 16919903
  • Quinzii, C. M. et al. (2008) X-linked dominant scapuloperoneal myopathy is due to mutation in the gene encoding four-and-a-half-LIM protein 1. Am. J. Hum. Genet. 82: 208-213. PubMed ID: 18179901
  • Schessl, J. et al. (2008).  Proteomic identification of FHL1 as the protein mutated in human reducing body myopathy. J. Clin. Invest. 118: 904-912.  PubMed ID: 18274675
  • Schessl, J. et al. (2009). Clinical, histological and genetic characterization of reducing body myopathy caused by mutations in FHL1. Brain 132: 452-464.  PubMed ID: 19181672
  • Schoser, B. et al. (2009) Consequences of mutations within the C terminus of the FHL1 gene. Neurology 73: 543-551. PubMed ID: 19687455
  • Selcen, D. et al. (2011) Reducing bodies and myofibrillar myopathy features in FHL1 muscular dystrophy. Neurology 77:1951-1959. PubMed ID: 22094483)
  • Shalaby, S. et al. 2009. Novel FHL1 mutations in fatal and benign reducing body myopathy. Neurology 72(4):375-6. PubMed ID: 19171836
  • Wilhelmsen, K. C. et al. (1996) Chromosome 12-linked autosomal dominant scapuloperoneal muscular dystrophy. Ann. Neurol. 39: 507-520.  PubMed ID: 8619529


Ordering Options

We offer several options when ordering sequencing tests. For more information on these options, see our Ordering Instructions page. To view available options, click on the Order Options button within the test description.

myPrevent - Online Ordering

  • The test can be added to your online orders in the Summary and Pricing section.
  • Once the test has been added log in to myPrevent to fill out an online requisition form.
  • PGnome sequencing panels can be ordered via the myPrevent portal only at this time.

Requisition Form

  • A completed requisition form must accompany all specimens.
  • Billing information along with specimen and shipping instructions are within the requisition form.
  • All testing must be ordered by a qualified healthcare provider.

For Requisition Forms, visit our Forms page

If ordering a Duo or Trio test, the proband and all comparator samples are required to initiate testing. If we do not receive all required samples for the test ordered within 21 days, we will convert the order to the most effective testing strategy with the samples available. Prior authorization and/or billing in place may be impacted by a change in test code.

Specimen Types

Specimen Requirements and Shipping Details

PGxome (Exome) Sequencing Panel

PGnome (Genome) Sequencing Panel

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