Usher syndrome is characterized by hearing impairment and retinitis pigmentosa. Usher syndrome can be classified into 3 different types on the basis of clinical findings.
Clinical Classification of Usher Syndrome
Type | Hearing Impairment | Vestibular Impairment | Retinitis Pigmentosa |
---|---|---|---|
Type I | Congenital Severe-to-profound hearing loss | Severe | Onset in first decade of life |
Type II | Congenital Moderate-to-severe hearing loss | None | Onset in first or second decade of life |
Type III | Variable progressive hearing loss | Variable | Variable |
MOLECULAR Classification of Usher Syndrome
n/a = not applicable
Note 1: The existence of the USH1A locus has been refuted by Gerber et al., 2006.
Note 2: In 2012, mutations in CIB2 were reported to cause Usher syndrome type 1J (Riazuddin et al., 2012). This assertion was questioned in 2018 (Booth et al., 2018), and in 2025 Riazuddin et al. published a correction: Riazuddin et al., 2025.
Note 3: USH2B, initially reported in Hmani et al., 1999, was later retracted by Hmani-Aifa et al., 2009.
Note 4: Mutations in PDZD7 were initially reported to cause digenic Usher syndrome type 2 with ADGRV1 (Ebermann et al., 2010), but this association has been called in to question. Mutations in PDZD7 have been shown to cause non-syndromic hearing loss only and not Usher syndrome (Booth et al., 2015).
Note 5: Puffenberger et al., 2012 by whole exome sequencing identified a homozygous mutation c.1361A>C (p.Tyr454Ser) in the HARS1 gene in a patient with RP, progressive hearing loss and episodic psychosis. The patient is part of the Old Order Amish community. The authors identified three other individuals with a similar phenotype to be homozygous for the same variant. The frequency of this allele in the Old Order Amish community is ~1.5%, the authors suggest it is a founder mutation. Functional assays suggest the pathogenic mechanism is due to over activity of HARS1. Of note 80 other homozygous variants were identified in this individual. This manuscript also reports 4 other novel genes for other phenotypes, with similar limited evidence. Some have called this report in to question and the gene has not yet been replicated as a cause of Usher syndrome in other populations.