Document Detail

USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21-q21.1.
Jump to Full Text
MedLine Citation:
PMID:  22718019     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
We ascertained two large Pakistani consanguineous families (PKDF231 and PKDF608) segregating profound hearing loss, vestibular dysfunction, and retinitis pigmentosa; the defining features of Usher syndrome type 1 (USH1). To date, seven USH1 loci have been reported. Here, we map a novel locus, USH1K, on chromosome 10p11.21-q21.1. In family PKDF231, we performed a genome-wide linkage screen and found a region of homozygosity shared among the affected individuals at chromosome 10p11.21-q21.1. Meiotic recombination events in family PKDF231 define a critical interval of 11.74 cM (20.20 Mb) bounded by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM). Affected individuals of family PKDF608 were also homozygous for chromosome 10p11.21-q21.1-linked STR markers. Of the 85 genes within the linkage interval, PCDH15, GJD4, FZD4, RET and LRRC18 were sequenced in both families, but no potential pathogenic mutation was identified. The USH1K locus overlaps the non-syndromic deafness locus DFNB33 raising the possibility that the two disorders may be caused by allelic mutations.
Authors:
Thomas J Jaworek; Rashid Bhatti; Noreen Latief; Shaheen N Khan; Saima Riazuddin; Zubair M Ahmed
Related Documents :
15158929 - Duplication 15q14 --> pter: a rare chromosomal abnormality underlying bipolar affective...
11353439 - De novo partial duplication of chromosome 7p in a male with autistic disorder.
9285799 - The human cox10 gene is disrupted during homologous recombination between the 24 kb pro...
8071969 - Charcot-marie-tooth disease in northern sweden: pedigree analysis and the presence of t...
9894799 - The evaluation of 15q proximal duplications by fish.
15605909 - Inherited tandem duplication of the x chromosome: dup(x)(q13.2-q21.2) in a family.
12764379 - Patterns of bcr/abl gene rearrangements by interphase fluorescence in situ hybridizatio...
24260699 - Karyotypes of some medium-sized dytiscidae (agabinae and colymbetinae) (coleoptera).
11793659 - Sex- and age-of-onset-based locus heterogeneity in asthma.
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, N.I.H., Intramural; Research Support, Non-U.S. Gov't     Date:  2012-06-21
Journal Detail:
Title:  Journal of human genetics     Volume:  57     ISSN:  1435-232X     ISO Abbreviation:  J. Hum. Genet.     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-25     Completed Date:  2013-04-01     Revised Date:  2013-07-12    
Medline Journal Info:
Nlm Unique ID:  9808008     Medline TA:  J Hum Genet     Country:  England    
Other Details:
Languages:  eng     Pagination:  633-7     Citation Subset:  IM    
Affiliation:
Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA.
Export Citation:
APA/MLA Format     Download EndNote     Download BibTex
MeSH Terms
Descriptor/Qualifier:
Adolescent
Adult
Alleles
Cadherins / genetics
Child
Chromosome Mapping / methods*
Chromosomes, Human, Pair 10 / genetics*
Female
Gene Frequency
Genetic Loci*
Genetic Predisposition to Disease
Genome-Wide Association Study
Hearing Loss, Sensorineural / genetics
Homozygote
Humans
Lod Score
Male
Meiosis
Middle Aged
Pakistan / ethnology
Pedigree
Recombination, Genetic
Usher Syndromes / genetics*
Young Adult
Grant Support
ID/Acronym/Agency:
R00 DC009287/DC/NIDCD NIH HHS; R01 DC011803/DC/NIDCD NIH HHS; R01 DC011803/DC/NIDCD NIH HHS
Chemical
Reg. No./Substance:
0/Cadherins; 0/PCDH15 protein, human
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

Full Text
Journal Information
Journal ID (nlm-journal-id): 9808008
Journal ID (pubmed-jr-id): 20962
Journal ID (nlm-ta): J Hum Genet
Journal ID (iso-abbrev): J. Hum. Genet.
ISSN: 1434-5161
ISSN: 1435-232X
Article Information
Download PDF

License:
nihms-submitted publication date: Day: 25 Month: 2 Year: 2013
Electronic publication date: Day: 21 Month: 6 Year: 2012
Print publication date: Month: 10 Year: 2012
pmc-release publication date: Day: 01 Month: 4 Year: 2013
Volume: 57 Issue: 10
First Page: 633 Last Page: 637
PubMed Id: 22718019
ID: 3596105
DOI: 10.1038/jhg.2012.79
ID: NIHMS381016

USH1K, a novel locus for type I Usher syndrome, maps to chromosome 10p11.21-q21.1
Thomas J. Jaworek1
Khitab Gul1
Naureen Latief2
Shaheen N. Khan2
Saima Riazuddin13
Zubair M Ahmed134
1Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Medical Center, and Department of Ophthalmology, College of Medicine, University of Cincinnati, Ohio 45229, USA
2National Center of Excellence in Molecular Biology, Punjab University, Lahore, Pakistan
3Division of Pediatric Otolaryngology Head & Neck Surgery, Cincinnati Children's Hospital Research Foundation, and Department of Otolaryngology, College of Medicine, University of Cincinnati, Ohio 45229, USA
4Institute of Biotechnology, Bahauddin Zakariya University, Multan 60800, Pakistan
Correspondence: Corresponding author: Zubair M. Ahmed, PhD, Division of Pediatric Ophthalmology, Cincinnati Children's Hospital Research Foundation, 3333 Burnet Ave, LocR2.2409; MLC 7003, Cincinnati, OH, 45229, USA., Tel.: 513-636-4718, Fax: 513-803-0740, zubair.ahmed@cchmc.org

Introduction

Usher syndrome causing genes have provided unexpected insights into developmental and biochemical processes shared by the eye and ear.1,2 Usher syndrome (USH) is neurosensory disorder affecting both hearing and vision in humans.3,4 A molecular diagnosis study suggested a frequency of 1/6000 individuals afflicted with USH in the U.S.5 Among the three defined clinical subtypes, USH type I (USH1) is the most genetically heterogeneous. To date, seven loci for USH1, three loci for USH2 and one locus for USH3 and genes for nine of them have been described.6-17 All of the USH proteins, including myosin VIIa (MIM 276903), cadherin 23 (MIM 605516), protocadherin 15 (MIM 605514), harmonin (MIM 605242), SANS (MIM 607696), usherin (MIM 608400), GPR98 (MIM 602851), whirlin (MIM 607928) and clarin-1 (MIM 606397), are thought to interact to form a large macromolecular complex,1,18 which is essential for auditory and visual functions. Furthermore, growing evidence suggests that USH proteins are localized in inner ear stereocilia bundles and are part of mechano-transduction machinery, and in the retina, largely within the molecular network tethering cilium to photoreceptor cells.1,11,19-26 However, the molecular identities of many essential components of these structures are unknown, precluding our understanding of the precise mechanisms of human hearing and vision.

The USH gene discovery process requires investigation of large human families segregating for USH, followed by genetic mapping and positional identification of causal mutations. Consanguineous families, plentiful in the Pakistani population, represent a rich resource for gene discovery research. Here we report two consanguineous Pakistani families in which the USH1 phenotype is linked to a novel USH1 locus, USH1K, on chromosome 10p11.21-q21.1.


Material and Methods
Subject enrollment

This study was approved by IRB Committee at the Cincinnati Children's Hospital Research Foundation, USA (2009-0684; 2010-0291), the IRB at the National Centre of Excellence in Molecular Biology (NCEMB), Lahore, Pakistan (FWA00001758) and the Combined Neuroscience IRB at the National Institutes of Health, USA (OH-93-N-016). Written informed consent was obtained from all adult subjects and parents of minor subjects under the age of 18 years. Subjects in this study were ascertained from Punjab province of Pakistan. Probands were initially identified at schools for the deaf in Punjab, Pakistan. National Centre of Excellence in Molecular Biology (NCEMB), Lahore, Pakistan enrolled the families in this study and performed clinical evaluation in collaboration with National Institutes of Health. Genotyping and sequencing of the DNA samples from the participating individuals was carried out at the Cincinnati Children's Hospital Research Foundation, USA.

Clinical evaluation

We performed medical history interviews to find obvious syndromic and environmental causes of hearing loss. For some of the affected individuals, a physical examination was performed to detect signs, symptoms or stigmata of other disorders such as Waardenburg or Pendred syndromes. Affected subjects underwent a general otological examination, including otoscopic examination and audiometry. Hearing was evaluated in some affected and unaffected subjects by pure-tone air- and bone-conduction audiometry with or without tympanometry. No air-bone gaps were observed in any tested individuals. Vestibular function was assessed by tandem gait and Romberg testing. Funduscopic examinations were performed by an ophthalmologist to confirm the absence or presence of retinitis pigmentosa.

DNA isolation, genotyping and linkage analysis

Genomic DNA was extracted from peripheral blood samples using a standard protocol.27 We performed a genome-wide scan in family PKDF231 for homozygosity among offspring of consanguineous marriages using 388 STR markers (v2.5 ABI Prism Linkage Mapping Set, Applied Biosystems, Foster City, CA) and an ABI Prism 3730 Genetic Analyzer. Alleles were assigned using Genscan and Genotyper software (Applied Biosystems). Linkage in family PKDF608 was identified by screening with STR markers linked to chromosome 10p11.21-q21.1.

LOD score calculations

Marker order and map distances are from the Marshfield genetic map (http://research.marshfieldclinic.org/). Two-point LOD scores were calculated with Superlink online version 1.5 (http://bioinfo.cs.technion.ac.il/superlink-online/). We assumed a recessive mode of inheritance, with full penetrance of USH in homozyotes and no phenocopies. The disease allele frequency was set at 0.001 with equal meiotic recombination frequencies for males and females. Short tandem repeat allele frequencies were defined by genotype analyses of 100 unaffected Pakistani individuals.

Candidate genes

We identified candidate USH1K genes on the UCSC Human Genome Browser (http://genome.ucsc.edu/). PCDH15, GJD4, FZD4, RET, and LRRC18 genes were sequenced in both PKDF231 and PKDF608 families using the primers flanking all of the exonic and adjacent intronic sequences. PCR, sequencing conditions and mutation analysis procedures were performed essentially as described.28,29


Results
Clinical description

At the time of examination, the ages of the affected individuals in family PKDF231 (Figure 1a) ranged from 12 to 26 years, while the ages of the affected individuals of family PKDF608 (Figure 1a) ranged from 18 to 45 years. All affected individuals in both families displayed congenital bilateral profound, sensorineural hearing loss (Figure 1b). Both in family PKDF231 and PKDF608, deaf individuals had delayed onset of independent ambulation, consistent with vestibular dysfunction, which was further confirmed by tandem gait ability and by using the Romberg test. Funduscopic examination of two older affected individuals of both families PKDF231 [V:5 (24 yo) and V:7 (26 yo); Figure 1a] and PKDF608 [V:20 (45 yo) and V:21 (18 yo); Figure 1a] revealed signs of retinitis pigmentosa along with narrowing of retinal blood vessel, bone spicules and waxy appearance of disc. The severity of retinitis pigmentosa was directly related to the age of the patient and ranged from mild to the severe loss of vision.

Linkage mapping

We undertook a genome wide linkage analysis in family PKDF231. It initially showed suggestive evidence of linkage only to markers on chromosome 10p11.21-q21.1. Affected individuals were homozygous for markers in this interval while unaffected obligate carriers were heterozygous (Figure 1a). Additional markers were genotyped and haplotype analysis revealed a 11.74 cM interval of homozygosity delimited by markers D10S1780 (63.83 cM) and D10S546 (75.57 cM; Figure 2). A maximum two-point lod score (Zmax) of 3.82 at recombination fraction θ=0 was obtained for the marker D10S539 (Table 1). Chromosome 10p11.21-q21.1-linked STR markers were then used to screen additional families segregating USH or isolated recessive deafness. One additional family, PKDF608, was found to be segregating USH1 linked to markers in this region (Figure 1a). A maximum two-point lod score (Zmax) of 3.22 at recombination fraction θ=0 was obtained for the marker D10S539 (Table 1).

Part of PCDH15 gene, mutant alleles are responsible for USH1F/DFNB23 phenotype in humans,7,28-30 is present within the distal breakpoint therefore we considered it a candidate for the USH1 phenotype. Full sequencing of PCDH15 in the genomic DNA from two affected individuals from each family along with normal hearing sibling did not reveal any functional mutations. Therefore, HUGO nomenclature committee assigned USH1K designation for the locus defined by families PKDF231 and PKDF608. Linkage interval of USH1K locus is approximately 20.20 Mb delimited by markers D10S1780 and D10S546 and harbor 85 candidate genes (Figure 2). The USH1K critical interval overlaps DFNB33 (MIM 607239), a locus for non-syndromic recessively inherited hearing loss that was previously mapped between markers D10S193 and D10S1784.(ref 31) We next considered the possibility that mutations of a single gene might underlie both USH1K and DFNB33. If so, the mutated gene is located between markers D10S1780 and D10S1784, which spans 19.12 Mb (UCSC human genome browser, Figure 2). On this assumption we examined the overlapping linkage interval of USH1K and DFNB33 and found same 85 genes (Figure 2). Analysis of data reported in a massively parallel signature sequencing libraries of mRNA from inner ear tissues32 and SHIELD database (https://shield.hms.harvard.edu/) reveal 53 of the 85 genes are expressed in the inner ear (Figure 2). The coding exons and flanking intronic sequence of additional four candidate genes GJD4, FZD8, RET and LRRC18 were sequenced in two affected individuals from each of the two USH1K families analyzed in this study, and no pathogenic sequence variants were found.


Discussion

Haplotype analysis of two families revealed a 11.74 cM region of homozygosity for USH1K on chromosome 10p11.21-q21.1. Families PKDF231 and PKDF608 each have unique haplotypes across this region, and therefore probably segregate different mutant USH1 alleles. The USH1K locus overlaps the DFNB33 locus on chromosome 10 and these two hearing disorders may be due to allelic mutations. Mutant alleles of four of the known USH1 genes, MYO7A, USH1C, CDH23 and PCDH15 are responsible for both non-syndromic hearing loss and USH.2,7-10,13,14,28,33-35 However, it is also plausible that these two loci are non-allelic.

Besides, USH1K and DFNB33 loci, human chromosome 10q also harbor two other loci for Usher syndrome type 1 and nonsyndromic hearing loss, USH1D/DFNB12 and USH1F/DFNB23.(ref 6,7,9,10,33) USH1D/DFNB12 locus is approximately 17.10 Mb telomeric to USH1K locus, while part of the PCDH15 gene, responsible for USH1F/DFNB23, lies within the distal boundary of USH1K (Figure 2). Sequencing of all the known coding and non-coding exons and 100 bp flanking exon-intron junctions of PCDH15 in both USH1K families did not reveal any pathogenic mutation. Although it is possible that PCDH15 may harbor cryptic mutations in cochlear-specific regulatory regions leading to USH1 in these two families, however, statistical analysis did not provide significant evidence of linkage of the USH1 phenotype segregating in USH1K family PKDF231 to PCDH15 intronic STR marker (D10S546; Table 1). There have been precedents for two closely associated or partially overlapping deafness loci in human, for example, DFNB36 and DFNB96, DFNB3 and DFNB85, DFNB35 and 14q23.1-q31.1 loci.36-39

In the linkage interval common to USH1K and DFNB33 there appears to be 85 known genes, out of which 53 are expressed in the inner ear. The candidate deafness genes in the critical USH1K/DFNB33 interval are GJD4, FZD4, RET and LRRC18 (Figure 2). GJD4 (MIM 611922) encodes the gap junction protein connexin 40.1. Mutations in several different connexin sub-units have been identified in individuals suffering with either non-syndromic or syndromic deafness.40FZD4 (MIM 604579) encodes a seven-transmembrane domain protein that belongs to frizzled receptor gene family. FZD4 plays a central role in the inner ear vascular development through Wnt signaling pathway.41RET (MIM 164761), a member of cadherin superfamily, encodes a receptor tyrosine kinase.42 Mutations in RET also cause Hirschsprung disease (MIM 142623), in which hearing loss is sometime detected.43,44LRRC18 encodes a leucine rich repeat containing protein member 18. Mutations in a different family member, LRTOMT (also known as LRRC51; MIM 612414), have been implicated in non-syndromic hearing loss.45-47 However, sequencing of these four candidate genes in both USH1K families did not reveal any potential pathogenic variant. All of the 85 candidate genes and conserved sequences in the USH1J/DFNB33 interval will now need to be screened for mutant alleles. Rather than continuing hierarchical sequencing of candidate genes based on function or expression, future studies will employ massively parallel sequencing of genomic DNA from the affected individuals of these families enriched for the entire USH1J critical interval.

USH mutations are estimated to be responsible for more than 50% of deaf-blindness, 8 to 33% of patients thought to have isolated RP, and 3 to 6% of patients thought to have isolated deafness.48-50 Effects of hearing loss on quality of life include difficulty in understanding speech and social isolation. In routine life, deaf people are strongly dependent on their vision, and blind people on their hearing, while individuals with Usher syndrome (USH) are deficient in both senses and thus suffer exacerbated quality-of-life effects. Ultimately, by limiting one's ability to communicate and interact, hearing and vision impairments impact cognitive, emotional and social development, making the development of intervention strategies a clinically significant long-term goal of the current research. Mapping of USH1K is a first step for understanding the molecular mechanisms resulting in Usher syndrome.


Notes

FN2Conflict of Interest: None

The authors are grateful to the families who made this research possible. These families were ascertained using the intramural funds from NIDCD DC000039-15 to Thomas B. Friedman. We thank R. Amjad Ali and Hashim Raza for technical assistance and Tom Friedman for his suggestions regarding this manuscript. This work was supported by the Higher Education Commission and Ministry of Science and Technology, Islamabad, Pakistan, to Sh.R.; the International Center for Genetic Engineering and Biotechnology, Trieste, Italy under project CRP/PAK08-01 contract no. 08/009 to Sh.R.; Cincinnati Children's Hospital Research Foundation (CCHMC) Intramural Research Funds, to S.R. and Z.M.A.; National Institute on Deafness and Other Communication Disorders (NIDCD/NIH) research grants R00 DC009287 to Z.M.A. and R01 DC011803 to S.R. Z.M.A. is also a recipient of an RPB Career Development Award.


References
1. Kremer H,van Wijk E,Marker T,Wolfrum U,Roepman R. Usher syndrome: molecular links of pathogenesis, proteins and pathwaysHum Mol Genet15 Spec No 2R26270Year: 200616987892
2. Petit C. Usher syndrome: from genetics to pathogenesisAnnu Rev Genomics Hum Genet227197Year: 200111701652
3. Smith RJ,et al. Clinical diagnosis of the Usher syndromes. Usher Syndrome ConsortiumAm J Med Genet50328Year: 19948160750
4. Ahmed ZM,Riazuddin S,Wilcox ER. The molecular genetics of Usher syndromeClin Genet6343144Year: 200312786748
5. Kimberling WJ,et al. Frequency of Usher syndrome in two pediatric populations: Implications for genetic screening of deaf and hard of hearing childrenGenet Med125126Year: 201020613545
6. Ahmed ZM,et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1FAm J Hum Genet692534Year: 200111398101
7. Alagramam KN,et al. Mutations in the novel protocadherin PCDH15 cause Usher syndrome type 1FHum Mol Genet10170918Year: 200111487575
8. Bitner-Glindzicz M,et al. A recessive contiguous gene deletion causing infantile hyperinsulinism, enteropathy and deafness identifies the Usher type 1C geneNat Genet265660Year: 200010973248
9. Bolz H,et al. Mutation of CDH23, encoding a new member of the cadherin gene family, causes Usher syndrome type 1DNat Genet2710812Year: 200111138009
10. Bork JM,et al. Usher syndrome 1D and nonsyndromic autosomal recessive deafness DFNB12 are caused by allelic mutations of the novel cadherin-like gene CDH23Am J Hum Genet682637Year: 200111090341
11. Ebermann I,et al. A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing lossHum Genet12120311Year: 200717171570
12. Joensuu T,et al. Mutations in a novel gene with transmembrane domains underlie Usher syndrome type 3Am J Hum Genet6967384Year: 200111524702
13. Verpy E,et al. A defect in harmonin, a PDZ domain-containing protein expressed in the inner ear sensory hair cells, underlies Usher syndrome type 1CNat Genet26515Year: 200010973247
14. Weil D,et al. Defective myosin VIIA gene responsible for Usher syndrome type 1BNature374601Year: 19957870171
15. Weil D,et al. Usher syndrome type I G (USH1G) is caused by mutations in the gene encoding SANS, a protein that associates with the USH1C protein, harmoninHum Mol Genet1246371Year: 200312588794
16. Weston MD,et al. Genomic structure and identification of novel mutations in usherin, the gene responsible for Usher syndrome type IIaAm J Hum Genet661199210Year: 200010729113
17. Weston MD,Luijendijk MW,Humphrey KD,Moller C,Kimberling WJ. Mutations in the VLGR1 gene implicate G-protein signaling in the pathogenesis of Usher syndrome type IIAm J Hum Genet7435766Year: 200414740321
18. El-Amraoui A,Petit C. Usher I syndrome: unravelling the mechanisms that underlie the cohesion of the growing hair bundle in inner ear sensory cellsJ Cell Sci1184593603Year: 200516219682
19. Ahmed ZM,et al. The tip-link antigen, a protein associated with the transduction complex of sensory hair cells, is protocadherin-15J Neurosci26702234Year: 200616807332
20. Kazmierczak P,et al. Cadherin 23 and protocadherin 15 interact to form tip-link filaments in sensory hair cellsNature4498791Year: 200717805295
21. Maerker T,et al. A novel Usher protein network at the periciliary reloading point between molecular transport machineries in vertebrate photoreceptor cellsHum Mol Genet177186Year: 200817906286
22. Overlack N,Maerker T,Latz M,Nagel-Wolfrum K,Wolfrum U. SANS (USH1G) expression in developing and mature mammalian retinaVision Res4840012Year: 200817923142
23. Lagziel A,et al. Expression of cadherin 23 isoforms is not conserved: implications for a mouse model of Usher syndrome type 1DMol Vis15184357Year: 200919756182
24. Goodyear RJ,Forge A,Legan PK,Richardson GP. Asymmetric distribution of cadherin 23 and protocadherin 15 in the kinocilial links of avian sensory hair cellsJ Comp Neurol518428897Year: 201020853507
25. Caberlotto E,et al. Usher type 1G protein sans is a critical component of the tip-link complex, a structure controlling actin polymerization in stereociliaProc Natl Acad Sci U S A108582530Year: 201121436032
26. Grati M,Kachar B. Myosin VIIa and sans localization at stereocilia upper tip-link density implicates these Usher syndrome proteins in mechanotransductionProc Natl Acad Sci U S A1081147681Year: 201121709241
27. Grimberg J,et al. A simple and efficient non-organic procedure for the isolation of genomic DNA from bloodNucleic Acids Res178390Year: 19892813076
28. Ahmed ZM,et al. Mutations of the protocadherin gene PCDH15 cause Usher syndrome type 1FAm J Hum Genet692534Year: 200111398101
29. Ahmed ZM,et al. Gene structure and mutant alleles of PCDH15: nonsyndromic deafness DFNB23 and type 1 Usher syndromeHum Genet12421523Year: 200818719945
30. Ben-Yosef T,et al. A mutation of PCDH15 among Ashkenazi Jews with the type 1 Usher syndromeN Engl J Med348166470Year: 200312711741
31. Belguith H,et al. Re-assigning the DFNB33 locus to chromosome 10p11.23-q21.1Eur J Hum Genet171224Year: 200918781188
32. Peters LM,et al. Signatures from tissue-specific MPSS libraries identify transcripts preferentially expressed in the mouse inner earGenomics89197206Year: 200717049805
33. Ahmed ZM,et al. PCDH15 is expressed in the neurosensory epithelium of the eye and ear and mutant alleles are responsible for both USH1F and DFNB23Hum Mol Genet12321523Year: 200314570705
34. Ahmed ZM,et al. Nonsyndromic recessive deafness DFNB18 and Usher syndrome type IC are allelic mutations of USHICHum Genet11052731Year: 200212107438
35. Riazuddin S,et al. Mutation spectrum of MYO7A and evaluation of a novel nonsyndromic deafness DFNB2 allele with residual functionHum Mutat29502511Year: 200818181211
36. Ansar M,et al. A new autosomal recessive nonsyndromic hearing impairment locus DFNB96 on chromosome 1p36.31-p36.13Journal of human genetics568668Year: 201121937999
37. Naz S,et al. Mutations of ESPN cause autosomal recessive deafness and vestibular dysfunctionJournal of medical genetics415915Year: 200415286153
38. Shahin H,et al. Five novel loci for inherited hearing loss mapped by SNP-based homozygosity profiles in Palestinian familiesEuropean journal of human genetics : EJHG1840713Year: 201019888295
39. Friedman TB,et al. A gene for congenital, recessive deafness DFNB3 maps to the pericentromeric region of chromosome 17Nature genetics98691Year: 19957704031
40. Scott CA,Kelsell DP. Key functions for gap junctions in skin and hearingBiochem J43824554Year: 201121834795
41. Xu Q,et al. Vascular development in the retina and inner ear: control by Norrin and Frizzled-4, a high-affinity ligand-receptor pairCell11688395Year: 200415035989
42. Traugott AL,Moley JF. The RET ProtooncogeneCancer Treat Res15330319Year: 201019957232
43. Skinner R,Irvine D. Hirschsprung's disease and congenital deafnessJ Med Genet103379Year: 19734774830
44. Liang JC,Juarez CP,Goldberg MF. Bilateral bicolored irides with Hirschsprung's disease. A neural crest syndromeArch Ophthalmol1016973Year: 19836849656
45. Ahmed ZM,et al. Mutations of LRTOMT, a fusion gene with alternative reading frames, cause nonsyndromic deafness in humansNat Genet40133540Year: 200818953341
46. Vanwesemael M,et al. A 1 bp deletion in the dual reading frame deafness gene LRTOMT causes a frameshift from the first into the second reading frameAm J Med Genet A155A20213Year: 201121739586
47. Du X,et al. A catechol-O-methyltransferase that is essential for auditory function in mice and humansProc Natl Acad Sci U S A1051460914Year: 200818794526
48. Boughman JA,Vernon M,Shaver KA. Usher syndrome: definition and estimate of prevalence from two high-risk populationsJ Chronic Dis36595603Year: 19836885960
49. Brownstein Z,et al. The R245X mutation of PCDH15 in Ashkenazi Jewish children diagnosed with nonsyndromic hearing loss foreshadows retinitis pigmentosaPediatr Res559951000Year: 200415028842
50. Vernon M. Usher's syndrome--deafness and progressive blindness. Clinical cases, prevention, theory and literature surveyJ Chronic Dis2213351Year: 19694897966

Article Categories:
  • Article

Keywords: deafness, DFNB33, retinitis pigmentosa, Usher syndrome, USH1K, vestibular dysfunction, 10p11.21-q21.1.

Previous Document:  Subtelomeric deletions of 1q43q44 and severe brain impairment associated with delayed myelination.
Next Document:  Four novel C20orf54 mutations identified in Brown-Vialetto-Van Laere syndrome patients.