{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T22:11:19Z","timestamp":1760739079279,"version":"build-2065373602"},"reference-count":22,"publisher":"BMJ","issue":"9","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["J Med Genet"],"published-print":{"date-parts":[[1996,9]]},"abstract":"<jats:p>The Usher syndromes are a group of autosomal recessive disorders characterised by retinitis pigmentosa (RP) with congenital, stable (non-progressive) sensorineural hearing loss. Profound deafness, RP, and no vestibular responses are features of Usher type I, whereas moderate to severe hearing loss and RP with normal vestibular function describe Usher type II. The gene responsible for most cases of Usher II, USH2a, is on chromosome 1q41; at least one other Usher II gene (as yet unlinked) is known to exist. Usher III presents with a progressive hearing loss that can mimic the audiometric profile seen in Usher II. A gene causing Usher III in a group of Finnish families, USH3, resides on chromosome 3q. Since the phenotypes for Usher II and III overlap, it is important to determine how frequently Usher IIa, Usher IIb, and Usher III occur in a clinical population of non-Usher I patients. DNA was collected from 29 Dutch families and genotyped with six DNA markers known to flank the USH2a gene closely, and with five markers that flank USH3. Results of haplotype and linkage analysis were consistent with linkage to the USH2a locus in 26 of these 29 Dutch families. Three families displayed no linkage to 1q41 markers, and one of these three families appeared unlinked to 3q markers as well; current haplotypes of the other two families are inconclusive for linkage with the USH3 locus without further genotyping. While an A test for heterogeneity of USH2a was statistically significant, no convincing evidence of linkage to USH3 was found in this Dutch sample. Consequently, the frequency of the unlinked variety of Usher IIa (Usher IIb) in The Netherlands was estimated as 0.104. To determine if marker alleles could be used to differentiate Usher type IIa from Usher IIb, parental chromosomes of the 26 Usher IIa families were analysed for significant non-random association of specific alleles from flanking loci with USH2a, but no linkage disequilibrium was observed in this Dutch population.<\/jats:p>","DOI":"10.1136\/jmg.33.9.753","type":"journal-article","created":{"date-parts":[[2008,11,10]],"date-time":"2008-11-10T15:37:21Z","timestamp":1226331441000},"page":"753-757","source":"Crossref","is-referenced-by-count":9,"title":["Genetic heterogeneity of Usher syndrome type II in a Dutch population."],"prefix":"10.1136","volume":"33","author":[{"given":"S","family":"Pieke-Dahl","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"van Aarem","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A","family":"Dobin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C W","family":"Cremers","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"W J","family":"Kimberling","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"239","published-online":{"date-parts":[[1996,9,1]]},"reference":[{"issue":"138","key":"ref_1","first-page":"1","article-title":"Retinitis pigmentosa combined with congenital deafness; with vestibulo-cerebellar ataxia and neural abnormality in a proportion of cases","volume":"1959","author":"Hallgren, B.","unstructured":"Hallgren B. Retinitis pigmentosa combined with congenital deafness; with vestibulo-cerebellar ataxia and neural abnormality in a proportion of cases. Acta Psychiatr Scand Suppl 1959;138:1-101.","journal-title":"Acta Psychiatr Scand Suppl"},{"key":"ref_2","first-page":"63","article-title":"Clinical and molecular genetics of Usher syndrome","volume":"6","author":"Kimberling, W.J.; Moller, C.","year":"1995","unstructured":"Kimberling WJ, Moller C. Clinical and molecular genetics of Usher syndrome. _Am Acad Audiol 1995;6:63-72.","journal-title":"_Am Acad Audiol"},{"key":"ref_3","first-page":"32","article-title":"Clinical diagnosis of the Usher syndromes","volume":"50","author":"Smith, R.J.H.; Berlin, C.J.; Hejmancik, J.F.","year":"1995","unstructured":"Smith RJH, Berlin CJ, Hejmancik JF, et al. Clinical diagnosis of the Usher syndromes. Am _7 Med Genet 1995; 50:32-8.","journal-title":"Am _7 Med Genet"},{"key":"ref_4","first-page":"4955","article-title":"Usher's and Hallgren's syndrome","volume":"23","author":"Merin, S.; Abraham, F.A.; Auerbach, E.","year":"1974","unstructured":"Merin S, Abraham FA, Auerbach E. Usher's and Hallgren's syndrome. Acta Genet Med Gemellol (Roma) 1974;23:4955.","journal-title":"Acta Genet Med Gemellol (Roma)"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"863","DOI":"10.1177\/000348948909801106","article-title":"Progressive hearing loss in Usher's syndrome","volume":"98","author":"Karjalainen, S.; Pakarinen, L.; Terasvirta, M.; Vartiainen, Kaariainen H.; E.","year":"1989","unstructured":"Karjalainen S, Pakarinen L, Terasvirta M, Kaariainen H. Vartiainen E. Progressive hearing loss in Usher's syndrome. Ann Otol Rhinol Laryngol 1989;98:863-6.","journal-title":"Ann Otol Rhinol Laryngol"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1093\/hmg\/4.1.93","article-title":"Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q","volume":"4","author":"Sankila, E.M.; Pakarinen, L.; Kaariainen, H.","year":"1995","unstructured":"Sankila EM, Pakarinen L, Kaariainen H, et al. Assignment of an Usher syndrome type III (USH3) gene to chromosome 3q. Hum Mol Genet 1995;4:93-8.","journal-title":"Hum Mol Genet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1016\/0888-7543(90)90546-7","article-title":"Localization of Usher syndrome type II to chromosome 1 q","volume":"7","author":"Kimberling, W.J.; Weston, M.D.; Moller, C.","year":"1990","unstructured":"Kimberling WJ, Weston MD, Moller C, et al. Localization of Usher syndrome type II to chromosome 1 q. Genomics 1990;7:245-9.","journal-title":"Genomics"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"250","DOI":"10.1016\/0888-7543(90)90547-8","article-title":"Mapping recessive ophthalmic diseases: linkage of the locus for Usher syndrome type II to a DNA marker on chromosome lq","volume":"7","author":"Lewis, R.A.; Otterud, B.; Stauffer, D.; Lalouel, J.M.; Leppert, M.","year":"1990","unstructured":"Lewis RA, Otterud B, Stauffer D, Lalouel JM, Leppert M. Mapping recessive ophthalmic diseases: linkage of the locus for Usher syndrome type II to a DNA marker on chromosome lq. Genomics 1990;7:250-6.","journal-title":"Genomics"},{"key":"ref_9","first-page":"105","article-title":"Usher syndrome type I is not linked to DIS81 (pTHH 33): evidence for genetic heterogeneity","volume":"33","author":"Kaplan, J.; Guasconi, G.; Bonneau, D.","year":"1990","unstructured":"Kaplan J, Guasconi G, Bonneau D, et al. Usher syndrome type I is not linked to DIS81 (pTHH 33): evidence for genetic heterogeneity. Ann Genet (Paris) 1990;33:105-8.","journal-title":"Ann Genet (Paris)"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/S0888-7543(05)80120-X","article-title":"A gene for Usher syndrome type I (USHIA) maps to chromosome 14q","volume":"14","author":"Kaplan, J.; Gerber, S.; Bonneau, D.","year":"1992","unstructured":"Kaplan J, Gerber S, Bonneau D, et al. A gene for Usher syndrome type I (USHIA) maps to chromosome 14q. Genomics 1992;14:979-87.","journal-title":"Genomics"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"988","DOI":"10.1016\/S0888-7543(05)80121-1","article-title":"Linkage of Usher syndrome type I gene (USHIB) to the long arm of chromosome 11","volume":"14","author":"Kimberling, W.J.; Moller, C.G.; Davenport, S.","year":"1992","unstructured":"Kimberling WJ, Moller CG, Davenport S, et al. Linkage of Usher syndrome type I gene (USHIB) to the long arm of chromosome 11. Genonmics 1992;14:988-94.","journal-title":"Genonmics"},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"995","DOI":"10.1016\/S0888-7543(05)80122-3","article-title":"Localization of two genes for Usher syndrome type I to chromosome 11","volume":"14","author":"Smith, R.J.H.; Lee, E.C.; Kimberling, W.J.","year":"1992","unstructured":"Smith RJH, Lee EC, Kimberling WJ, et al. Localization of two genes for Usher syndrome type I to chromosome 11. Genomics 1992;14:995-1002.","journal-title":"Genomics"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"60","DOI":"10.1038\/374060a0","article-title":"Defective myosin VIIA gene responsible for Usher syndrome type 1 B","volume":"374","author":"Weil, D.; Blanchard, S.; Kaplan, J.","year":"1995","unstructured":"Weil D, Blanchard S, Kaplan J, et al. Defective myosin VIIA gene responsible for Usher syndrome type 1 B. Nature 1995;374:60-1.","journal-title":"Nature"},{"article-title":"The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type Ila (USH2a) gene in 1q41","author":"Sumegi, J.; Wang, J.Y.; Zhen, D.K.","key":"ref_14","unstructured":"Sumegi J, Wang JY, Zhen DK, et al. The construction of a yeast artificial chromosome (YAC) contig in the vicinity of the Usher syndrome type Ila (USH2a) gene in 1q41. Genomics (in press)."},{"key":"ref_15","first-page":"843","article-title":"Genetic heterogeneity of Usher syndrome type II..7 Med","volume":"30","author":"Pieke-Dahl, S.; Kimberling, W.J.; Gorin, M.B.","year":"1993","unstructured":"Pieke-Dahl S, Kimberling WJ, Gorin MB, et al. Genetic heterogeneity of Usher syndrome type II..7 Med Genet 1993; 30:843-8.","journal-title":"Genet"},{"key":"ref_16","first-page":"216","article-title":"Gene mapping of Usher syndrome type IIa: localisation of the gene to a 2.1-cM segment on chromosome 1q41","volume":"56","author":"Kimberling, W.J.; Weston, M.D.; Moller, C.","year":"1995","unstructured":"Kimberling WJ, Weston MD, Moller C, et al. Gene mapping of Usher syndrome type IIa: localisation of the gene to a 2.1-cM segment on chromosome 1q41. Am. Hum Geniet 1995;56:216-23.","journal-title":"Am. Hum Geniet"},{"article-title":"Stable and progressive hearing loss in type 2A Usher syndrome","author":"van Aarem A; PLM, Huygen; AJLG, Pinckers","key":"ref_17","unstructured":"van Aarem A, Huygen PLM, Pinckers AJLG, et al. Stable and progressive hearing loss in type 2A Usher syndrome. Ann Otol Rhinol Laryngol (in press)."},{"key":"ref_18","article-title":"Acoustics -Audiometric test methods. Part I","author":"8253-1, ISO","year":"1985","unstructured":"ISO 8253-1. Acoustics -Audiometric test methods. Part I. Basic pure tone air and bone conduction threshold audiomietry, 1985."},{"key":"ref_19","article-title":"Acoustics -","author":"389, ISO","year":"1985","unstructured":"ISO 389. Acoustics - Standard reference zero for the calibration ofpure tone air conduction audiometers, 1985."},{"article-title":"ISO 7029. Acoustics - Thresholds of hearing by air conduictionl as a function of age and sex for otologically normzal personis","year":"1984","key":"ref_20","unstructured":"ISO 7029. Acoustics - Thresholds of hearing by air conduictionl as a function of age and sex for otologically normzal personis, 1984."},{"key":"ref_21","first-page":"482","article-title":"Multilocus linkage analysis in humans: detection of linkage and estimation of recombination","volume":"37","author":"Lathrop, G.M.; Lalouel, J.M.; Julier, C.; Ott, J.","year":"1985","unstructured":"Lathrop GM, Lalouel JM, Julier C, Ott J. Multilocus linkage analysis in humans: detection of linkage and estimation of recombination. Am. Hum Genet 1985;37:482-98.","journal-title":"Am. Hum Genet"},{"key":"ref_22","article-title":"Analysis of human genetic linkage","author":"Ott, J.","year":"1991","unstructured":"Ott J. Analysis of human genetic linkage. Baltimore: Johns Hopkins Univerity Press, 1991."}],"container-title":["Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1136\/jmg.33.9.753","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,17]],"date-time":"2025-10-17T21:59:54Z","timestamp":1760738394000},"score":1,"resource":{"primary":{"URL":"https:\/\/jmg.bmj.com\/lookup\/doi\/10.1136\/jmg.33.9.753"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1996,9]]},"references-count":22,"journal-issue":{"issue":"9","published-online":{"date-parts":[[1996,9,1]]},"published-print":{"date-parts":[[1996,9]]}},"alternative-id":["10.1136\/jmg.33.9.753"],"URL":"https:\/\/doi.org\/10.1136\/jmg.33.9.753","relation":{},"ISSN":["0022-2593","1468-6244"],"issn-type":[{"type":"print","value":"0022-2593"},{"type":"electronic","value":"1468-6244"}],"subject":[],"published":{"date-parts":[[1996,9]]}}}