A novel gene for Usher syndrome type 2: mutations in the long isoform of whirlin are associated with retinitis pigmentosa and sensorineural hearing loss.

Abstract:

:Usher syndrome is an autosomal recessive condition characterized by sensorineural hearing loss, variable vestibular dysfunction, and visual impairment due to retinitis pigmentosa (RP). The seven proteins that have been identified for Usher syndrome type 1 (USH1) and type 2 (USH2) may interact in a large protein complex. In order to identify novel USH genes, we followed a candidate strategy, assuming that mutations in proteins interacting with this "USH network" may cause Usher syndrome as well. The DFNB31 gene encodes whirlin, a PDZ scaffold protein with expression in both hair cell stereocilia and retinal photoreceptor cells. Whirlin represents an excellent candidate for USH2 because it binds to Usherin (USH2A) and VLGR1b (USH2C). Genotyping of microsatellite markers specific for the DFNB31 gene locus on chromosome 9q32 was performed in a German USH2 family that had been excluded for all known USH loci. Patients showed common haplotypes. Sequence analysis of DFNB31 revealed compound heterozygosity for a nonsense mutation, p.Q103X, in exon 1, and a mutation in the splice donor site of exon 2, c.837+1G>A. DFNB31 mutations appear to be a rare cause of Usher syndrome, since no mutations were identified in an additional 96 USH2 patients. While mutations in the C-terminal half of whirlin have previously been reported in non-syndromic deafness (DFNB31), both alterations identified in our USH2 family affect the long protein isoform. We propose that mutations causing Usher syndrome are probably restricted to exons 1-6 that are specific for the long isoform and probably crucial for retinal function. We describe a novel genetic subtype for Usher syndrome, which we named USH2D and which is caused by mutations in whirlin. Moreover, this is the first case of USH2 that is allelic to non-syndromic deafness.

journal_name

Hum Genet

journal_title

Human genetics

authors

Ebermann I,Scholl HP,Charbel Issa P,Becirovic E,Lamprecht J,Jurklies B,Millán JM,Aller E,Mitter D,Bolz H

doi

10.1007/s00439-006-0304-0

subject

Has Abstract

pub_date

2007-04-01 00:00:00

pages

203-11

issue

2

eissn

0340-6717

issn

1432-1203

journal_volume

121

pub_type

杂志文章
  • Pairing of X and Y chromosomes, non-inactivation of X-linked genes, and the maleness factor.

    abstract::In this paper observations are summarized and speculations discussed, and it is suggested that some loci on the distal short arm of the X chromosome (Xp) are not randomly inactivated in the female, because they are within the proximal part of the pairing segment between Xp and Yp. This peculiarity of gene expression m...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00303003

    authors: Polani PE

    更新日期:1982-01-01 00:00:00

  • Quantitative analysis of C bands in chromosomes 1, 9, and 16 of Brazilian Indians and Caucasoids.

    abstract::Densitometric C-band measurements in chromosomes 1, 9, and 16 of 394 Indians and 40 Caucasoids living in Brazil are reported. No significant intratribal variability in the average length of these regions was observed, and the intertribal variation showed no consistent patterns. But the Caucasoids always presented lowe...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00271168

    authors: Erdtmann B,Salzano FM,Mattevi MS,Flores RZ

    更新日期:1981-01-01 00:00:00

  • The mutational demography of protein C deficiency.

    abstract::The geographical distribution and prevalence of 256 single base-pair substitutions (105 of them being different) within the coding region of the human protein C (PROC) gene were correlated with their initial likelihoods of generation. A significant positive correlation was observed between these "mutational likelihood...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00207369

    authors: Krawczak M,Reitsma PH,Cooper DN

    更新日期:1995-08-01 00:00:00

  • Fine-mapping the genetic basis of CRP regulation in African Americans: a Bayesian approach.

    abstract::Basal levels of C-reactive protein (CRP) have been associated with disease, particularly future cardiovascular events. Twin studies estimate 50% CRP heritability, so the identification of genetic variants influencing CRP expression is important. Existing studies in populations of European ancestry have identified nume...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s00439-008-0517-5

    authors: Rhodes B,Morris DL,Subrahmanyan L,Aubin C,de Leon CF,Kelly JF,Evans DA,Whittaker JC,Oksenberg JR,De Jager PL,Vyse TJ

    更新日期:2008-07-01 00:00:00

  • Three-point linkage analysis employing C3 and 19cen markers assigns the myotonic dystrophy gene to 19q.

    abstract::In seven large families with myotonic dystrophy (DM) comprising 102 individuals, linkage studies were performed employing restriction fragment length polymorphisms in the complement component 3 gene and the 19cen C banding heteromorphism as genetic markers. Three-point linkage analysis excludes DM from the 19cen-C3 se...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00281077

    authors: Friedrich U,Brunner H,Smeets D,Lambermon E,Ropers HH

    更新日期:1987-03-01 00:00:00

  • Arginase deficiency manifesting delayed clinical sequelae and induction of a kidney arginase isozyme.

    abstract::Deficiency of liver arginase (AI) is characterized clinically by hyperargininemia, progressive mental impairment, growth retardation, spasticity, and periodic episodes of hyperammonemia. The rarest of the inborn errors of urea cycle enzymes, it has been considered the least life-threatening, by virtue of the typical a...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00230212

    authors: Grody WW,Kern RM,Klein D,Dodson AE,Wissman PB,Barsky SH,Cederbaum SD

    更新日期:1993-03-01 00:00:00

  • Delineation of marker chromosomes by reverse chromosome painting using only a small number of DOP-PCR amplified microdissected chromosomes.

    abstract::A new procedure for determining the chromosomal origin of marker chromosomes has been carried out. The origin of marker chromosomes that were unidentifiable by standard banding techniques could be verified by reverse chromosome painting. This technique includes microdissection, followed by in vitro DNA amplification a...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00201567

    authors: Viersbach R,Schwanitz G,Nöthen MM

    更新日期:1994-06-01 00:00:00

  • Identification of 96 single nucleotide polymorphisms in eight genes involved in iron metabolism: efficiency of bioinformatic extraction compared with a systematic sequencing approach.

    abstract::Single nucleotide polymorphisms (SNPs) can significantly contribute to the characterization of the genes predisposing to iron overloads or deficiencies. We report an SNP survey of coding and non-coding regions of eight genes involved in iron metabolism, by two successive methods. First, we made use of the public domai...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s004390100599

    authors: Douabin-Gicquel V,Soriano N,Ferran H,Wojcik F,Palierne E,Tamim S,Jovelin T,McKie AT,Le Gall JY,David V,Mosser J

    更新日期:2001-10-01 00:00:00

  • The association of SNPs in ADIPOQ, ADIPOR1, and ADIPOR2 with insulin sensitivity in a cohort of adolescents and their parents.

    abstract::Few studies have examined the association of SNPs in the adiponectin (ADIPOQ) and adiponectin receptor 1 and 2 (ADIPOR1, ADIPOR2) genes with the euglycemic clamp, i.e. the gold standard measure of insulin sensitivity. The association of comprehensive tag SNPs in these genes with insulin sensitivity was examined in a c...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s00439-008-0595-4

    authors: Rasmussen-Torvik LJ,Pankow JS,Jacobs DR Jr,Steinberger J,Moran A,Sinaiko AR

    更新日期:2009-02-01 00:00:00

  • A G to A transition at the last nucleotide of exon 6 of the gamma c gene (868G-->A) may result in either a splice or missense mutation in patients with X-linked severe combined immunodeficiency.

    abstract::We report here that a defect of the interleukin common gamma subunit (gamma c) in X-linked severe combined immunodeficiency (XSCID) previously known as a missense mutation resulted instead in exon skipping in a Japanese XSCID patient. The phenotype of the patient was consistent with that of typical XSCID, and his Epst...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s004390050907

    authors: Kanai N,Yanai F,Hirose S,Nibu K,Izuhara K,Tani T,Kubota T,Mitsudome A

    更新日期:1999-01-01 00:00:00

  • Parental generalized EEG alpha activity predisposes to spike wave discharges in offspring.

    abstract::Familial and twin studies have shown that the individual variability of the normal human electroencephalogram (EEG) is largely genetically determined. In epileptology, these genetic parameters of the EEG background activity are almost totally neglected. The aim of the present study has been to investigate whether a sp...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00210302

    authors: Doose H,Castiglione E,Waltz S

    更新日期:1995-12-01 00:00:00

  • Studies on three rare fragile sites. 2q13, 12q13, and 17p12 segregating in one family.

    abstract::Three fragile sites 2q13, 12q13, and 17p12 were found in one family. In the index case, who was first investigated in 1969 for low birth weight and bilateral inguinal hernia, three tissues were examined, blood, marrow, and skin. Three of the family have been reinvestigated after 17 years. Cultures for sister chromatid...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00291608

    authors: Romain DR,Columbano-Green LM,Smythe RH,Parfitt RG,Gebbie OB,Chapman CJ

    更新日期:1986-06-01 00:00:00

  • Galactose-1-phosphate-uridyltransferase (E.C. 2.7.7.11): a simple routine method for detecting individuals heterozygous for the silent allele Gt 0.

    abstract::A simple routine method for detecting individuals who are heterozygous for the silent gene Gt 0 is presented. This method consists of a combination of electrophoresis and densitometry. The results confirm the theoretical expectation that these individuals would exhibit about 50% of the enzyme activity found in the cor...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00278984

    authors: Siebert G,Kömpf J,Ritter H

    更新日期:1980-01-01 00:00:00

  • Assignment of the structural gene coding for albumin to human chromosome 4.

    abstract::Albumin is a developmentally regulated serum protein synthesized in the liver mainly during adulthood. Family studies using variant forms of albumin established autosomal linkage between albumin and group-specific component protein (GS). Since GC has been assigned to human chromosome 4, albumin can be indirectly assig...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00304551

    authors: Kao FT,Hawkins JW,Law ML,Dugaiczyk A

    更新日期:1982-01-01 00:00:00

  • Amplified product length polymorphism (APLP): a novel strategy for genotyping the ABO blood group.

    abstract::We present a simple rapid reproducible polymerase chain reaction based technique, termed amplified product length polymorphism (APLP), as a new strategy for primer design for ABO genotyping. The method involves the use of primers differing in length and permits the identification of the major ABO genotypes (A1, A2, B,...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s004390050306

    authors: Watanabe G,Umetsu K,Yuasa I,Suzuki T

    更新日期:1997-01-01 00:00:00

  • Chromosomes in the Cornelia de Lange syndrome.

    abstract::This paper summarizes previous chromosomal studies in patients with the Cornelia de Lange syndrome showing abnormal karyotypes. We report on 45 cases of the Cornelia de Lange syndrome clinically examined by one of us (B.B.) and chromosomally studied using several different methods. Two abnormal karyotypes were found: ...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00295457

    authors: Beck B,Mikkelsen M

    更新日期:1981-01-01 00:00:00

  • Low incidence of deletion of the esterase D locus in retinoblastoma patients.

    abstract::Esterase D was quantitatively measured in the red blood cells from three patients from three separate kindreds who had abnormalities of chromosome 13. The esterase D activity was proportional to the number of copies of the q14 region of chromosome 13 present. These findings confirm published data localizing the estera...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00327114

    authors: Dryja TP,Bruns GA,Gallie B,Petersen R,Green W,Rapaport JM,Albert DM,Gerald PS

    更新日期:1983-01-01 00:00:00

  • Somatic mutations in planar cell polarity genes in neural tissue from human fetuses with neural tube defects.

    abstract::Extensive studies that have sought causative mutation(s) for neural tube defects (NTDs) have yielded limited positive findings to date. One possible reason for this is that many studies have been confined to analyses of germline mutations and so may have missed other, non-germline mutations in NTD cases. We hypothesiz...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s00439-020-02172-0

    authors: Tian T,Lei Y,Chen Y,Karki M,Jin L,Finnell RH,Wang L,Ren A

    更新日期:2020-10-01 00:00:00

  • Advances in osteoclast biology resulting from the study of osteopetrotic mutations.

    abstract::Osteopetrosis is the result of mutations affecting osteoclast function. Careful analyses of osteopetrosis have provided instrumental information on bone remodeling, including the coupling of bone formation to bone resorption. Based on a range of novel genetic mutations and the resulting osteoclast phenotypes, we discu...

    journal_title:Human genetics

    pub_type: 杂志文章,评审

    doi:10.1007/s00439-008-0583-8

    authors: Segovia-Silvestre T,Neutzsky-Wulff AV,Sorensen MG,Christiansen C,Bollerslev J,Karsdal MA,Henriksen K

    更新日期:2009-01-01 00:00:00

  • Evidence for a major gene (RP10) for autosomal dominant retinitis pigmentosa on chromosome 7q: linkage mapping in a second, unrelated family.

    abstract::Retinitis pigmentosa is a genetically heterogeneous form of retinal degeneration, which has X-linked, autosomal recessive and autosomal dominant forms. The disease genes in families with autosomal dominant retinitis pigmentosa (adRP) have been linked to six loci, on 3q, 6p, 7p, 7q, 8q and 19q. In a large American fami...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00225078

    authors: McGuire RE,Gannon AM,Sullivan LS,Rodriguez JA,Daiger SP

    更新日期:1995-01-01 00:00:00

  • Functional polymorphisms in NFκB1/IκBα predict risks of chronic obstructive pulmonary disease and lung cancer in Chinese.

    abstract::Lung inflammation is the major pathogenetic feature for both chronic obstructive pulmonary disease (COPD) and lung cancer. The nuclear factor-kappa B (NFκB) and its inhibitor (IκB) play crucial roles in inflammatory. Here, we tested the hypothesis that single nucleotide polymorphisms (SNPs) in NFκB/IκB confer consiste...

    journal_title:Human genetics

    pub_type: 临床试验,杂志文章

    doi:10.1007/s00439-013-1264-9

    authors: Huang D,Yang L,Liu Y,Zhou Y,Guo Y,Pan M,Wang Y,Tan Y,Zhong H,Hu M,Lu W,Ji W,Wang J,Ran P,Zhong N,Zhou Y,Lu J

    更新日期:2013-04-01 00:00:00

  • An additional allelic variant of the CYP2D6 gene causing impaired metabolism of sparteine.

    abstract::The identification of a novel CYP2D6 allele from a healthy Caucasian poor metabolizer was achieved by using a previously described polymerase chain reaction/single-strand conformation polymorphism strategy. Among the four point mutations that this allele carries, a missense mutation in exon 1 (212 G-->A or D6-H) seems...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF02281880

    authors: Marez D,Legrand M,Sabbagh N,Lo-Guidice JM,Boone P,Broly F

    更新日期:1996-05-01 00:00:00

  • The human apolipoprotein B 3' hypervariable region: detection of eight new alleles and comparisons of allele frequencies in blacks and whites.

    abstract::We investigated common length polymorphisms in the hypervariable region located 3' to the human gene encoding apolipoprotein B (APOB 3' HVR) as part of the "Pathobiological Determinants of Atherosclerosis in Youth (PDAY)" study. PDAY is a multicenter study of young persons who died of external causes (accident, homici...

    journal_title:Human genetics

    pub_type: 杂志文章,多中心研究

    doi:10.1007/BF00217775

    authors: Hixson JE,Powers PK,McMahan CA

    更新日期:1993-06-01 00:00:00

  • G6PD Ciudad de la Habana: a new slow variant with deficiency found in a Cuban family.

    abstract::A new G6PD variant has been detected in a Cuban male and there is no evidence of associated hematological abnormalities. The main characteristics of this variant, moderate deficiency, slow electrophoretic mobility, increased utilization of the substrate analogues, and a different chromatographic behavior, indicate tha...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00329141

    authors: González R,Estrada M,García M,Gutierrez A

    更新日期:1980-01-01 00:00:00

  • The frequency of lysosomal storage diseases in The Netherlands.

    abstract::We have calculated the relative frequency and the birth prevalence of lysosomal storage diseases (LSDs) in The Netherlands based on all 963 enzymatically confirmed cases diagnosed during the period 1970-1996. The combined birth prevalence for all LSDs is 14 per 100,000 live births. Glycogenosis type II is the most fre...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s004399900075

    authors: Poorthuis BJ,Wevers RA,Kleijer WJ,Groener JE,de Jong JG,van Weely S,Niezen-Koning KE,van Diggelen OP

    更新日期:1999-07-01 00:00:00

  • Exploiting the proteome to improve the genome-wide genetic analysis of epistasis in common human diseases.

    abstract::One of the central goals of human genetics is the identification of loci with alleles or genotypes that confer increased susceptibility. The availability of dense maps of single-nucleotide polymorphisms (SNPs) along with high-throughput genotyping technologies has set the stage for routine genome-wide association stud...

    journal_title:Human genetics

    pub_type: 杂志文章,评审

    doi:10.1007/s00439-008-0522-8

    authors: Pattin KA,Moore JH

    更新日期:2008-08-01 00:00:00

  • Allele-specific transcription factor binding to common and rare variants associated with disease and gene expression.

    abstract::Genome-wide association studies (GWAS) have identified a large number of disease-associated SNPs, but in few cases the functional variant and the gene it controls have been identified. To systematically identify candidate regulatory variants, we sequenced ENCODE cell lines and used public ChIP-seq data to look for tra...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/s00439-016-1654-x

    authors: Cavalli M,Pan G,Nord H,Wallerman O,Wallén Arzt E,Berggren O,Elvers I,Eloranta ML,Rönnblom L,Lindblad Toh K,Wadelius C

    更新日期:2016-05-01 00:00:00

  • Attempt to calculate the allele frequency distribution of a TaqI RFLP detected by the highly polymorphic probe YNH24.

    abstract::To improve the analysis of parentage testing with the additional technique of DNA polymorphisms, the usefulness of probe YNH24 was studied. The allele frequency distribution of restriction fragments detected by probe YNH24 on TaqI-digested genomic DNA from 100 unrelated individuals was determined. For this purpose, th...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00196240

    authors: van Eede PH,Cuypers TM,de Lange GG

    更新日期:1990-03-01 00:00:00

  • Parental age and seasonal variation in the births of children with sporadic retinoblastoma: a mutation-epidemiologic study.

    abstract::Statistical analysis of parental age data from 225 sporadic cases of bilateral retinoblastoma, plus ten sporadic cases of chromosome deletion or translocation involving 13q14 that was identified as of paternal origin, revealed no evidence of paternal or maternal age effect. Parental exposure to ionizing radiation or c...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00208931

    authors: Matsunaga E,Minoda K,Sasaki MS

    更新日期:1990-01-01 00:00:00

  • Linkage analysis of the Duffy blood group marker with several chromosome 1 genes in an extended pedigree with Charcot-Marie-Tooth disease.

    abstract::We have recently demonstrated tight linkage of the Duffy blood group marker to the alpha-spectrin gene in an extended pedigree with Charcot-Marie-Tooth neuropathy. To determine a more precise location of the Duffy blood group locus on the chromosome 1 map we have tested several more chromosome 1 genes for linkage with...

    journal_title:Human genetics

    pub_type: 杂志文章

    doi:10.1007/BF00278994

    authors: Raeymaekers P,Van Broeckhoven C,Backhovens H,Wehnert A,Muylle L,De Jonghe P,Gheuens J,Martin JJ,Vandenberghe A

    更新日期:1989-02-01 00:00:00