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MYO7A gene

Overview

Gene (OMIM No.)
Function of gene/protein
  • Member of unconventional myosin family
  • Actin-binding motor protein
  • Required for normal development and function of the inner ear hair cell stereocilia
  • Expressed in the photoreceptors and retinal pigment epithelium (RPE) where it has multiple putative functions
Clinical phenotype
(OMIM phenotype no.)
Inheritance
  • Autosomal recessive
  • Autosomal dominant
Ocular features
Visual functionUsher syndrome
  • Nyctalopia with pre-adolescent onset
  • Peripheral visual field loss
  • Loss of central and colour vision in later life
Systemic features
  • Congenital, bilateral, severe to profound sensorineural hearing loss
  • Failed newborn hearing screen or hearing difficulties suspected in infancy
  • Vestibular dysfunction affecting balance from birth
Key investigations
  • Newborn hearing screen – otoacoustic emission and automated auditory brainstem response
  • Pure tone audiometry
  • Electrophysiology
  • Fundus autofluorescence (FAF): a ring of hyper-AF in the macula
  • Optical coherence tomography (OCT): progressive loss of outer retinal structures which spares the fovea initially; cystoid macular oedema may be detected
  • Kinetic perimetry
Molecular diagnosisNext generation sequencing
  • Targeted gene panels (retinal and deafness)
  • Whole exome sequencing
  • Whole genome sequencing
  • Targeted exome sequencing
Management
Therapies under research
Further information

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Additional information

Mutations in MYO7A have been associated with three different disorders: dominant and recessive non-syndromic hearing loss (DFNA11 and DFNB2, respectively), and Usher syndrome type 1B.[6-8] Evidence of clear genotype-phenotype correlations is lacking. It has been suggested that mutations that allow some residual motor protein function e.g. in-frame deletion c.5146_5148delGAG p.(Glu1716del), cause the milder non-syndromic phenotypes, whereas mutations associated with Usher type 1 e.g. c.1309G>A p.(Asp437Asn), have a more severe effect on protein function.[9] Others have proposed that null MYO7A alleles i.e. those with stop mutations within the motor domain coding region such as c.999T>C p.(Tyr333*), may cause milder visual dysfunction than missense variants owing to a lack of mutant protein contributing to disease pathology.[10] Significant correlations have not been reported in other patient populations with MYO7A mutations.[11] Mutations of MYO7A reported to cause DFNB2 are comparable to those causing Usher type 1, indicating that this phenotype may result from missed RP or there may be modifying factors which influence the phenotype.[12] MYO7A mutations have also been reported to cause a phenotype of unilateral auditory neuropathy in a Chinese family with Usher type 1[13] and Usher type 2 phenotypes.[14]

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References

  1.  Colella P, Sommella A, Marrocco E, et al. Myosin7a deficiency results in reduced retinal activity which is improved by gene therapy. PLoS One. 2013;8(8):e72027
  2.  Lopes VS, Boye SE, Louie CM, et al. Retinal gene therapy with a large MYO7A cDNA using adeno-associated virus. Gene Ther. Aug 2013;20(8):824-833
  3.  Trapani I, Colella P, Sommella A, et al. Effective delivery of large genes to the retina by dual AAV vectors. EMBO Mol Med. Feb 2014;6(2):194-211
  4.  Dyka FM, Boye SL, Chiodo VA, Hauswirth WW, Boye SE. Dual Adeno-Associated Virus Vectors Result in Efficient In Vitro and In Vivo Expression of an Oversized Gene, MYO7A. Human Gene Therapy Methods. Apr 2014;25(2):166-177
  5.  Colella P, Trapani I, Cesi G, et al. Efficient gene delivery to the cone-enriched pig retina by dual AAV vectors. Gene Ther. Apr 2014;21(4):450-456
  6.  Liu XZ, Walsh J, Mburu P, et al. Mutations in the myosin VIIA gene cause non-syndromic recessive deafness. Nat Genet. Jun 1997;16(2):188-190
  7.  Weil D, Kussel P, Blanchard S, et al. The autosomal recessive isolated deafness, DFNB2, and the Usher 1B syndrome are allelic defects of the myosin-VIIA gene. Nat Genet. Jun 1997;16(2):191-3
  8.  Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIA gene responsible for Usher syndrome type 1B. Nature. Mar 2 1995;374(6517):60-1
  9.  Riazuddin S, Nazli S, Ahmed ZM, et al. Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual function. Hum Mutat. Apr 2008;29(4):502-11
  10.  Jacobson SG, Cideciyan AV, Gibbs D, et al. Retinal disease course in Usher syndrome 1B due to MYO7A mutations. Invest Ophthalmol Vis Sci. 2011;52(11):7924-7936
  11.  Lenassi E, Saihan Z, Cipriani V, et al. Natural history and retinal structure in patients with Usher syndrome type 1 owing to MYO7A mutation. Ophthalmology. Feb 2014;121(2):580-7
  12.  Astuto LM, Kelley PM, Askew JW, et al. Searching for evidence of DFNB2. Am J Med Genet. May 15 2002;109(4):291-7
  13.  Xia H, Hu P, Yuan L, et al. A homozygous MYO7A mutation associated to Usher syndrome and unilateral auditory neuropathy spectrum disorder. Mol Med Rep. Oct 2017;16(4):4241-4246
  14.  Rong W, Chen X, Zhao K, et al. Novel and recurrent MYO7A mutations in Usher syndrome type 1 and type 2. PLoS One. 2014;9(5):e97808

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Updated on November 30, 2020
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