CLINICAL PRESENTATION AND DISEASE COURSE OF USHER SYNDROME BECAUSE OF MUTATIONS IN MYO7A OR USH2A.
OBJECTIVE
To evaluate differences in the visual phenotype and natural history of Usher syndrome caused by mutations in MYO7A or USH2A, the most commonly affected genes of Usher syndrome Type I (USH1) and Type II (USH2), respectively.


METHODS
Eighty-eight patients with a clinical diagnosis of USH1 (26 patients) or USH2 (62 patients) were retrospectively evaluated. Of these, 48 patients had 2 disease-causing mutations in MYO7A (10 USH1 patients), USH2A (33 USH2 patients), and other USH (5 patients) genes. Clinical investigation included best-corrected visual acuity, Goldmann visual field, fundus photography, electroretinography, and audiologic and vestibular assessments. Longitudinal analysis was performed over a median follow-up time of 3.5 years.


RESULTS
Patients carrying mutations in MYO7A had a younger age of onset of hearing and visual impairments than those carrying mutations in USH2A, leading to an earlier diagnosis of the disease in the former patients. Longitudinal analysis showed that visual acuity and visual field decreased more rapidly in subjects carrying MYO7A mutations than in those carrying USH2A mutations (mean annual exponential rates of decline of 3.92 vs. 3.44% and of 8.52 vs. 4.97%, respectively), and the former patients reached legal blindness on average 15 years earlier than the latter.


CONCLUSIONS
The current study confirmed a more severe progression of the retinal disease in USH1 patients rather than in USH2 patients. Furthermore, most visual symptoms (i.e., night blindness, visual acuity worsening) occurred at an earlier age in USH1 patients carrying mutations in MYO7A.
*Eye Clinic, Multidisciplinary Department of Medical, Surgical and Dental Sciences, Second University of Naples, Naples, Italy; †Institut de la Vision, UMRS 1120 INSERM/UPMC, Paris, France; ‡Audiology Unit, Department of Neuroscience, Reproductive and Odontostomatologic Sciences, University of Naples Federico II, Naples, Italy; §Centre for Ophthalmology, Institute for Ophthalmic Research, University of Tuebingen, Tuebingen, Germany; ¶Telethon Institute of Genetics and Medicine (TIGEM), Pozzuoli, Italy; **Medical Genetics, Department of Translational Medicine, Federico II University, Naples, Italy; and ††Institut Pasteur, Collège de France, Paris, France.
Francesco
F
Testa
Paolo
P
Melillo
Crystel
C
Bonnet
Vincenzo
V
Marcelli
Antonella
A
de Benedictis
Raffaella
R
Colucci
Beatrice
B
Gallo
Anne
A
Kurtenbach
Settimio
S
Rossi
Elio
E
Marciano
Alberto
A
Auricchio
Christine
C
Petit
Eberhart
E
Zrenner
Francesca
F
Simonelli
D000293:Adolescent; D000328:Adult; D004247:DNA / Q000235:genetics*; D004252:DNA Mutational Analysis; D018450:Disease Progression; D004596:Electroretinography; D016326:Extracellular Matrix Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008297:Male; D008875:Middle Aged; D009154:Mutation; D000081412:Myosin VIIa; D009218:Myosins / Q000235:genetics* / Q000378:metabolism; D010641:Phenotype; D012160:Retina / Q000000981:diagnostic imaging / Q000503:physiopathology; D012189:Retrospective Studies; D013997:Time Factors; D041623:Tomography, Optical Coherence; D052245:Usher Syndromes / Q000175:diagnosis / Q000235:genetics* / Q000503:physiopathology; D014792:Visual Acuity; D014794:Visual Fields; D055815:Young Adult
D016326:Extracellular Matrix Proteins; C000631455:MYO7A protein, human; D000081412:Myosin VIIa; C112735:USH2A protein, human; D004247:DNA; D009218:Myosins