Usher Syndrome, Type Iid

Watchlist

(log in to enable)

Retrieved

2019-09-22

Source

Omim

Trials

—

Genes

MYO7A, PCDH15, HARS1, PLD4, USH1C, ADGRV1, USH2A, CDH23, CEP250, ARSG, PROM1, CLRN1, ZDHHC24, CDH23-AS1, TRNS2, BBS1, GUCA1A, WHRN, USH1G, PDZD7, CIB2, GJB2, ESPN, HTC2, GC, CEP78, ABHD12, PCARE, GPR166P, LGR6, INTS2, VN1R17P, MRGPRX1, FADS6, MRGPRX3, MRGPRX4, ASIC5, GPR151, OXER1, LCA5, GPRC6A, VEZT, ACTB, MYO15A, PRPH2, ENG, FGF3, GBX2, MEF2C, MYO5B, NOTCH2, NUCB2, OMP, PEX6, RCVRN, RPGR, PHPT1, SOX3, STATH, USH1E, WFS1, FZD4, OTOF, CIB1, ASAH1, NINL, LPAR3, IMMT

Drugs

Adeno-associated virus serotype 8 containing the human RdCVF sequence and the human RdCVFL sequence, Combination of three adeno-associated viral vectors of serotype 8 containing the 5'-, the body- and the 3'- coding sequences of human CEP290 fused to inteins, Lentiviral vector containing the human MYO7A gene, Mixture of two adeno-associated viral vectors serotype 8 containing the 5'-half sequence of human MYO7A gene and the 3'-half sequence of human MYO7A gene

Interested in hearing about new therapies?

A number sign (#) is used with this entry because of evidence that type IID Usher syndrome (USH2D) is caused by homozygous or compound heterozygous mutation in the WHRN gene (607928) on chromosome 9q32. WHRN mutation has also been shown to cause a form of autosomal recessive nonsyndromic deafness, DFNB31 (607084).

Description

Usher syndrome is a clinically and genetically heterogeneous autosomal recessive disorder characterized by sensorineural hearing deficiencies at birth and later development of progressive retinitis pigmentosa (RP). It is the most frequent cause of combined deafness and blindness in adults and affects 3 to 6% of children born with hearing impairment. In brief, patients with Usher syndrome type II have mild hearing impairment with normal vestibular responses. Type II is the most common of the 3 Usher syndromes (Eudy et al., 1998).

See 276900 for clinical characterization of Usher syndrome types I, II, and III.

For a discussion of genetic heterogeneity of Usher syndrome type II, see USH2A (276901).

Clinical Features

Ebermann et al. (2007) studied a German family in which 2 sibs had mild to moderate congenital hearing impairment and retinitis pigmentosa without vestibular dysfunction. Haplotype analysis excluded known Usher syndrome loci, but the affected individuals shared common haplotypes for the markers of the DFNB31 locus.

Molecular Genetics

By sequence analysis of a German family with Usher syndrome type IID, Ebermann et al. (2007) identified compound heterozygosity for a nonsense mutation (607928.0002) and a splice site mutation (607928.0003) in the WHRN gene.

In 2 of 31 French USH2 patients who were not linked to the USH2A locus (608400), Besnard et al. (2012) identified homozygosity and compound heterozygosity for WHRN mutations, respectively (607928.0004; 607928.0005). Besnard et al. (2012) concluded that WHRN mutations account for a very small proportion of mutations causing USH2 (1.3%).

Genotype/Phenotype Correlations

Abadie et al. (2012) analyzed the audiologic findings in 100 USH2 patients, including 88 with USH2A (608400) mutations, 10 with GPR98 (602851) mutations, and 2 with WHRN mutations. The median age of diagnosis of hearing loss was 5 years (range, 8 months to 31 years), but some patients may have had earlier onset. Usher syndrome was diagnosed at a median age of 34.5 years. Most patients (76%) had moderate hearing loss and most (66%) had a gently down-sloping audiogram. The median pure tone average (PTA) was 59.7 dB. There were no significant differences between patients with USH2A and GPR98 mutations, but the GPR98 cases had a higher proportion of severe hearing loss (40%) compared to USH2A cases (16%). Among all groups, cut-off frequencies were noted at 500-1000 Hz. There was some intrafamilial variability. Overall, Abadie et al. (2012) concluded that it is not possible to predict the mutated gene from audiograms in patients with USH2.