Paternal Uniparental Heterodisomy With Partial Isodisomy of Chromosome 1 in a Patient With Retinitis Pigmentosa Without Hearing Loss and a Missense Mutation in the Usher Syndrome Type II Gene USH2A

AimsTo reveal the Usher syndrome type IIA (USH2A) gene variant profile in a large cohort of Chinese patients with non-syndromic retinitis pigmentosa (RP) or Usher syndrome type II (USH2) and to explore the genotype–phenotype correlation.MethodsTargeted exome capture plus next-generation sequencing confirmed that 284 patients from 260 unrelated Chinese families carried USH2A disease-associated variants. Both personal medical history and family histories were reviewed. Ocular examinations were performed and audiograms were recorded if hearing loss was suspected. The genotype–phenotype correlation was evaluated by statistical analyses.ResultsA total of 230 variants in the USH2A gene were identified, of which 90 (39.13%) were novel. The most common variants in the RP and USH2 probands were p.Cys934Trp and p.Tyr2854_2894del, respectively, and 26.42% and 63.64% of the alleles in the RP and USH2 groups were truncating, respectively. Patients harbouring biallelic truncating variants had a younger age at the initial clinical visit and symptom onset than patients with missense variants; furthermore, the patients with USH2 had a younger age at the initial clinical visit and nyctalopia onset compared with the patients with RP (p<0.001). For the patients with USH2, the age of nyctalopia onset was positively correlated with that of hearing loss (p<0.05, r=0.219). In addition, three pseudo-dominant pedigrees were identified carrying biallelic USH2A variants.ConclusionsThis study enrolled the largest cohort of Chinese patients with USH2A and identified the most prevalent USH2A variants in USH2 and RP. We found that the patients with USH2 had more truncating variants and experienced an earlier decline in visual function. The findings enhance the current knowledge of USH2A heterogeneity and provide valuable information for future therapies.

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Comprehensive screening of the USH2A gene in Usher syndrome type II and non-syndromic recessive retinitis pigmentosa

Experimental Eye Research ◽

10.1016/j.exer.2004.03.005 ◽

2004 ◽

Vol 79 (2) ◽

pp. 167-173 ◽

Cited By ~ 56

Author(s):

Babak Jian Seyedahmadi ◽

Carlo Rivolta ◽

Julia A. Keene ◽

Eliot L. Berson ◽

Thaddeus P. Dryja

Keyword(s):

Retinitis Pigmentosa ◽

Usher Syndrome ◽

Syndrome Type ◽

Type Ii ◽

Usher Syndrome Type

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A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss

Human Genetics ◽

10.1007/s00439-006-0304-0 ◽

2006 ◽

Vol 121 (2) ◽

pp. 203-211 ◽

Cited By ~ 131

Author(s):

Inga Ebermann ◽

Hendrik P. N. Scholl ◽

Peter Charbel Issa ◽

Elvir Becirovic ◽

Jürgen Lamprecht ◽

...

Keyword(s):

Hearing Loss ◽

Retinitis Pigmentosa ◽

Sensorineural Hearing Loss ◽

Usher Syndrome ◽

Sensorineural Hearing ◽

Syndrome Type ◽

Novel Gene ◽

Usher Syndrome Type

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Usher syndrome Type I in an adult Nepalese male: a rare case report

Nepalese Journal of Ophthalmology ◽

10.3126/nepjoph.v9i2.19271 ◽

2018 ◽

Vol 9 (2) ◽

pp. 203-205

Author(s):

Sabin Sahu ◽

Sanjay Kumar Singh

Keyword(s):

Hearing Loss ◽

Retinitis Pigmentosa ◽

Genetic Disorder ◽

Usher Syndrome ◽

Type I ◽

Syndrome Type ◽

Profound Hearing Loss ◽

Rare Case Report ◽

Different Populations ◽

Usher Syndrome Type

Usher syndrome, also known as retinitis pigmentosa-dysacusis syndrome, is an extremely rare genetic disorder, characterized by retinitis pigmentosa (RP) and congenital sensorineural hearing loss. It has been estimated to account for 3-6% of the congenitally deaf population, upto 8-33% of individuals with RP and half of all cases with combined deafness and blindness (Vernon M,1969; Boughman JA et al,1983). The prevalence of Usher syndrome have been reported to range from 3.5 to 6.2 per 100,000 in different populations (Vernon M,1969; Boughman JA et al,1983; Yan D et al, 2010).We report a case of Usher syndrome type I in an adult Nepalese male with typical congenital profound hearing loss, and night blindness secondary to retinitis pigmentosa.

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Novel mutations in the long isoform of the USH2A gene in patients with Usher syndrome type II or non-syndromic retinitis pigmentosa

Journal of Medical Genetics ◽

10.1136/jmg.2009.075143 ◽

2010 ◽

Vol 47 (7) ◽

pp. 499-506 ◽

Cited By ~ 68

Author(s):

T. L. McGee ◽

B. J. Seyedahmadi ◽

M. O. Sweeney ◽

T. P. Dryja ◽

E. L. Berson

Keyword(s):

Retinitis Pigmentosa ◽

Usher Syndrome ◽

Syndrome Type ◽

Type Ii ◽

Novel Mutations ◽

Usher Syndrome Type

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Hearing Loss in Usher Syndrome Type II is Nonprogressive

Annals of Otology Rhinology & Laryngology ◽

10.1177/000348940211101208 ◽

2002 ◽

Vol 111 (12) ◽

pp. 1108-1111 ◽

Cited By ~ 17

Author(s):

Christoph F. V. Reisser ◽

William J. Kimberling ◽

Christian R. Otterstedde

Keyword(s):

Hearing Loss ◽

Hearing Aids ◽

Visual Loss ◽

Usher Syndrome ◽

Autosomal Recessive Disorder ◽

Syndrome Type ◽

Type Ii ◽

Subjective Impression ◽

Communicative Abilities ◽

Usher Syndrome Type

Usher syndrome is an autosomal recessive disorder characterized by sensorineural hearing loss and progressive visual loss secondary to retinitis pigmentosa. In the literature, a possible progression of the moderate to severe hearing loss in Usher syndrome type II (Usher II) is controversial. We studied the development of the hearing loss of 125 patients with a clinical diagnosis of Usher syndrome type II intraindividually and interindividually by repeatedly performing complete audiological and neuro-otologic examinations. Our data show a very characteristic slope of the hearing curve in all Usher II patients and no clinically relevant progression of the hearing loss over up to 17 years. The subjective impression of a deterioration of the communicative abilities of Usher II patients must therefore be attributed to the progressive visual loss. The patients should be reassured that changes in their hearing abilities are unlikely and should be provided with optimally fitted modern hearing aids.

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