HUT (Hutterite)

Inheritance: autosomal recessive
Genes: PCDH15, MYO7A

 USH1F, USH1B

Sensorineural deafness
Retinitis pigmentosa
Vestibular dysfunction

Usher Syndrome

Clinical Characteristics

General description (for patients):  

The term Usher syndrome refers to a collection of conditions in which there is deafness and a progressive retinal degeneration causing severe night blindness.  Several types are known which as a group are responsible for the majority of cases with a combination of deafness and blindness.  Children may be born with profound hearing loss and and later develop severe vision loss in the first decade in the severe forms. Milder cases are simply considered hard of hearing while significant visual impairment does not occur until the third and fourth decades.  As a result of early hearing loss, speech may be significantly impaired.  Cataracts may develop at a relatively young age.

Medical description:  

Usher syndrome consists of a group of inherited autosomal recessive conditions with progressive pigmentary retinopathy and sensorineural deafness.  Individual syndromes can be separated by the age of onset and severity of the deafness and pigmentary retinopathy, as well as the degree of vestibular dysfunction.

Genetics:

Type 1F Usher syndrome results from an autosomal recessive mutation in the protocadherin-15 gene (PCDH15) located on chromosome 10 (10q21-q22).  It has been identified in two southern Alberta Hutterite male offspring of consanguineous matings in which there was a homozygous T deletion at nucleotide 1471 producing a frameshift that resulted in a premature stop codon.
Type 1B results from homozygous mutations in the myosin VIIA (MYO7A) gene (11q13.5) and has been identified in 4 individuals in two related Alberta Hutterite families.
Type IIIB is caused by homozygous mutations in HARS (5q31.3) and has been found among the Amish of Eastern Pennsylvania.

Treatment:

No treatment is known.

Prognosis:

Complete deafness and blindness.

Ancillary treatments and support:

Visual training and vocational rehabilitation.

Specialists and specialty centers:

Ophthalmologist, Audiologist, ENT.

References:

Alagramam, K.N., Yuan, H., Kuehn, M.H., Murcia, C.L., Wayne, S., Srikumari Srisailpathy, C.R., Lowry, R.B., Knaus, R., Van Laer, L., Bernier, F.P., Schwartz, S., Lee, C., Morton, C.C., Mullins, R.F., Ramesh, A., Van Camp, G., Hagemen, G.S., Woychik, R.P., and Smith, R.J.H.:  Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1F.  Hum. Mol. Genet. 10: 1709-1718, 2001.  PubMed ID: 11487575

Rebibo-Sabbah, A., Nudelman, I., Ahmed, Z.M., Baasov, T., and Ben-Yosef, T.: In vitro and ex vivo suppression by aminoglycosides of PCDH15 nonsense mutations underlying type 1 Usher syndrome.  Hum. Genet. 122: 373-381, 2007. PubMed ID: 17653769

Zhou Q, Lenger C, Smith R, Kimberling WJ, Ye M, Lehmann O, Macdonald I.
 Evidence of genetic heterogeneity in Alberta Hutterites with Usher syndrome type I. Mol Vis. 2012;18:1379-83. PubMed ID: 22690115.

Puffenberger EG, Jinks RN, Sougnez C, Cibulskis K, Willert RA, Achilly NP, Cassidy RP, Fiorentini CJ, Heiken KF, Lawrence JJ, Mahoney MH, Miller CJ, Nair DT, Politi KA, Worcester KN, Setton RA, Dipiazza R, Sherman EA, Eastman JT, Francklyn C, Robey-Bond S, Rider NL, Gabriel S, Morton DH, Strauss KA. Genetic mapping and exome sequencing identify variants associated with five novel diseases. PLoS One. 2012;7(1):e28936. Epub 2012 Jan 17. PubMed PMID: 22279524.

Resources:

Usher Syndome Support Group
National Consortium on Deaf-Blindness