Usher Syndrome, Type Ik

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Retrieved

2019-09-22

Source

Omim

Trials

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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

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Description

Usher syndrome type I is an autosomal recessive condition characterized by profound congenital hearing impairment with unintelligible speech, early retinitis pigmentosa (usually evident within the first decade), and constant vestibular dysfunction. Type I is distinguished from type II (276901) on the basis of severity of hearing loss and the extent of vestibular involvement. Type I patients are profoundly deaf, whereas type II patients are 'hard of hearing.' Vestibular function is defective in type I patients, whereas type II patients have normal vestibular function (Moller et al., 1989). Patients with type III (USH3; 276902) have progressive hearing loss.

For a discussion of genetic heterogeneity of Usher syndrome type I, see USH1 (276900).

Clinical Features

Jaworek et al. (2012) reported 2 consanguineous Pakistani families with Usher syndrome. The patients ranged in age from 12 to 45 years. All patients had congenital, bilateral, profound sensorineural hearing loss as well as delayed onset of independent ambulation, consistent with vestibular dysfunction. Funduscopic examination of 4 older individuals showed retinitis pigmentosa with narrowing of retinal blood vessels, bone spicules, and waxy appearance of the optic disc. The severity of retinitis pigmentosa correlated with the age of the patient, and ranged from mild to severe.

Inheritance

The transmission pattern of USH1K in the families reported by Jaworek et al. (2012) was consistent with autosomal recessive inheritance.

Mapping

By genomewide linkage analysis of a consanguineous Pakistani family with Usher syndrome, Jaworek et al. (2012) found linkage to an 11.74-cM region on chromosome 10p11.21-q21.1 between markers D10S1780 and D10S546 (maximum 2-point lod score of 3.82 at D10S539). A second Pakistani family with the disorder also showed linkage to this region (maximum 2-point lod score of 3.22 at D10S539). The locus, which was termed USH1K, showed some overlap with that of nonsyndromic deafness-33 (DFNB33; 607239). Several candidate genes within the disease interval were sequenced, including PCDH15 (605514), but no mutations were identified.