A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome

  title={A novel D458V mutation in the SANS PDZ binding motif causes atypical Usher syndrome},
  author={Ersan Kalay and Arjan Pm de Brouwer and Refik Çaylan and Sander B. Nabuurs and Bernd Wollnik and A. Tugay Karaguzel and J G Heister and Hidayet Erdol and Frans P. M. Cremers and Cwrj Cremers and Han G. Brunner and Hannie Kremer},
  journal={Journal of Molecular Medicine},
Homozygosity mapping and linkage analysis in a Turkish family with autosomal recessive prelingual sensorineural hearing loss revealed a 15-cM critical region at 17q25.1–25.3 flanked by the polymorphic markers D17S1807 and D17S1806. The maximum two-point lod score was 4.07 at θ=0.0 for the marker D17S801. The linkage interval contains the Usher syndrome 1G gene (USH1G) that is mutated in patients with Usher syndrome (USH) type 1g and encodes the SANS protein. Mutation analysis of USH1G led to… 
A frameshift mutation in SANS results in atypical Usher syndrome
A consanguineous family with four affected individuals with moderate to severe hearing loss, mild retinitis pigmentosa and normal vestibular function is reported, a phenotype which resembles an USH2 diagnosis.
Novel USH1G homozygous variant underlying USH2-like phenotype of Usher syndrome
The findings widen the spectrum of USH allelic disorders and strength the concept that variants in genes that are classically known as underlying one specific clinical USH subtype might result in unexpected phenotypes.
The contribution of GPR98 and DFNB31 genes to a Spanish Usher syndrome type 2 cohort
It is confirmed that mutations in GPR98 contribute a significant but minor role to Usher syndrome type 2, and the importance of including at least GPR 98 analysis for comprehensive USH2 molecular diagnosis is confirmed.
USH1G with unique retinal findings caused by a novel truncating mutation identified by genome-wide linkage analysis
The identification of a novel p.S243X truncating mutation in USH1G that segregated with the disease phenotype and was not present in 300 ethnically matched normal controls is reported and the first report of successful cochlear implants in this disease is presented.
CEP250 mutations associated with mild cone-rod dystrophy and sensorineural hearing loss in a Japanese family
The data indicate that mutations of CEP250 can cause mild CRD and SNHL in Japanese patients, and high-resolution retinal imaging analysis, such as AO, will be helpful in diagnosing CEP 250-associated disease.
Screening of the USH1G Gene among Spanish Patients with Usher Syndrome. Lack of Mutations and Evidence of a Minor Role in the Pathogenesis of the Syndrome
The Usher syndrome (USH) is an autosomal recessive hereditary disorder characterized by the association of sensorineural hearing loss, retinitis pigmentosa (RP) and, in some cases, vestibular
Genetics and pathological mechanisms of Usher syndrome
  • D. YanX. Liu
  • Biology, Medicine
    Journal of Human Genetics
  • 2010
A unifying hypothesis is that the USH proteins are integrated into a protein network that regulates hair bundle morphogenesis in the inner ear, which is important toward discovery of new molecular targets for diagnosis, prevention and treatment of this debilitating disorder.
Usher Syndrome: Genetics of a Human Ciliopathy
The genetics of Usher syndrome and the spectrum of mutations in USH genes are reviewed to identify possible mutation associations with the disease and provide an updated genotype–phenotype correlation.
Predicting candidate genes for human deafness disorders: a bioinformatics approach
A list of strong candidate genes encoded by the regions linked to various nonsyndromic hereditary hearing loss phenotypes are established by using a novel bioinformatic approach and provide a starting point for mutational analysis in well-characterized families.


Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1D
The data show that different mutations in CDH23 result in USH1D with a variable retinal phenotype, and it is shown that mutations in the mouse ortholog cause disorganization of inner ear stereocilia and deafness in the waltzer mouse.
Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmonin.
It is suggested that a functional network formed by the USH1B, C, D and G proteins is responsible for the correct cohesion of the hair bundle, and it is shown that SANS associates with harmonin, a PDZ domain-containing protein responsible for USH 1C.
Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23.
Genes causing nonsyndromic autosomal recessive deafness (DFNB12) and deafness associated with retinitis pigmentosa and vestibular dysfunction (USH1D) were previously mapped to overlapping regions of chromosome 10q21-q22, but mutations in a novel cadherin-like gene, CDH23, were found both in families with DFNB12 and in Families with USH1D.
CDH23 mutation and phenotype heterogeneity: a profile of 107 diverse families with Usher syndrome and nonsyndromic deafness.
Results of ophthalmologic examinations of the patients with nonsyndromic deafness have found asymptomatic RP-like manifestations, indicating that missense mutations may have a subtle effect in the retina.
A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C gene
The pattern of expression of the USH1C protein is consistent with the clinical features exhibited by individuals with the contiguous gene deletion and with isolated Usher type 1C.
A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1C
A gene underlying USH1C is identified, encoding a PDZ-domain–containing protein, harmonin, in a subtracted mouse cDNA library derived from inner ear sensory areas, and it is proposed that Ush1C also underlies the DFNB18 form of isolated deafness.
Defective myosin VIIA gene responsible for Usher syndrome type IB
Evidence is presented that a gene encoding myosin VIIA is responsible for USH1B and that USH IB appears as a primary cytoskeletal protein defect, which implicate the genes encoding other unconventional myosins and their interacting proteins as candidates for other genetic forms of Usher syndrome.
A novel claudin 16 mutation associated with childhood hypercalciuria abolishes binding to ZO-1 and results in lysosomal mistargeting.
Mutations in the gene coding for the renal tight junction protein claudin 16 cause familial hypomagnesemia with hypercalciuria and nephrocalcinosis, an autosomal recessive disorder of renal Ca(2+)
Variable Clinical Features in Patients with CDH23 Mutations (USH1D-DFNB12)
  • R. PenningsV. Topsakal C. Cremers
  • Medicine
    Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology
  • 2004
Recessive missense mutations in CDH23 lead to a milder phenotype (DFNB12) than splice-site mutations (USH1D); however, abnormal bilateral flecks, suggestive for lipofuscin accumulation, can be observed in DFNB12 patients.
Clinical and molecular genetics of Usher syndrome.
As progress towards the identification of theUsher genes is made, the clinician will gradually gain new and effective diagnostic procedures for the identification and delineation of the Usher syndromes.