{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,10,27]],"date-time":"2025-10-27T15:51:56Z","timestamp":1761580316753},"reference-count":52,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2005,6,7]],"date-time":"2005-06-07T00:00:00Z","timestamp":1118102400000},"content-version":"vor","delay-in-days":3753,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Am. J. Med. Genet."],"published-print":{"date-parts":[[1995,2,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Early onset familial Alzheimer's disease (AD) has an autosomal dominant mode of inheritance. Two genes are responsible for the majority of cases of this subtype of AD. Mutations in the \u03b2\u2010amyloid precursor protein (\u03b2APP) gene on chromosome 21 have been shown to completely cosegregate with the disease. We and others have previously described the clinical features of families with \u03b2APP mutations at the codon 717 locus in an attempt to define the phenotype associated with a valine to isoleucine (Val \u2192 Ile) or a valine to glycine (Val \u2192 Gly) change. More recently, a second locus for very early onset disease has been localized to chromosome 14. The results of linkage studies in some families suggesting linkage to both chromosomes have been explained by the suggestion of a second (centromeric) locus on chromosome 21. Here we report the clinical features and genetic analysis of a British pedigree (F74) with early onset AD in which neither the \u03b2APP locus nor any other chromosome 21 locus segregates with the disease, but in which good evidence is seen for linkage on the long arm of chromosome 14. In particular we report marker data suggesting that the chromosome 14 disease locus is close to D14S43 and D14S77. Given the likelihood that F74 represents a chromosome 14 linked family, we describe the clinical features and make a limited clinical comparison with the \u03b2APP717 Val \u2192 Ile and \u03b2APP717 Val \u2192 Gly encoded families that have been previously described. We conclude that although several previously reported clinical features occur to excess in early onset familial AD, no single clinical feature demarcates either the chromosome 14 or \u03b2APP codon 717 mutated families except mean age of onset. \u00a9 1995 Wiley\u2010Liss, Inc.<\/jats:p>","DOI":"10.1002\/ajmg.1320600109","type":"journal-article","created":{"date-parts":[[2005,6,11]],"date-time":"2005-06-11T18:15:43Z","timestamp":1118513743000},"page":"44-52","source":"Crossref","is-referenced-by-count":5,"title":["Clinical features of early onset, familial Alzheimer's disease linked to chromosome 14"],"prefix":"10.1002","volume":"60","author":[{"given":"Michael","family":"Mullan","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Craig","family":"Bennett","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cecilia","family":"Figueredo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David","family":"Hughes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rebecca","family":"Mant","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michael","family":"Owen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrew","family":"Warren","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Melvin","family":"McInnis","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Marshall","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Peter","family":"Lantos","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"John","family":"Collinge","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alison","family":"Goate","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Henry","family":"Houlden","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fiona","family":"Crawford","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2005,6,7]]},"reference":[{"key":"e_1_2_1_2_1","first-page":"229","article-title":"Characteristics of familial Alzheimer's disease in nine kindreds of Volga German ancestry","volume":"317","author":"Bird TD","year":"1989","journal-title":"Prog Clin Biol Res"},{"key":"e_1_2_1_3_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.114.512.797"},{"key":"e_1_2_1_4_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.8424174"},{"key":"e_1_2_1_5_1","doi-asserted-by":"publisher","DOI":"10.1038\/353844a0"},{"key":"e_1_2_1_6_1","doi-asserted-by":"publisher","DOI":"10.1038\/360672a0"},{"key":"e_1_2_1_7_1","first-page":"35","volume-title":"Alzheimer's Disease: Basic Mechanisms, Diagnosis, and Therapeutic Strategies","author":"Clark C","year":"1991"},{"key":"e_1_2_1_8_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.29.10.1402"},{"key":"e_1_2_1_9_1","doi-asserted-by":"publisher","DOI":"10.1159\/000133017"},{"key":"e_1_2_1_10_1","doi-asserted-by":"publisher","DOI":"10.1016\/0304-3940(91)90042-R"},{"key":"e_1_2_1_11_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.13.10.811"},{"key":"e_1_2_1_12_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/1.3.165"},{"key":"e_1_2_1_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-3956(75)90026-6"},{"key":"e_1_2_1_14_1","doi-asserted-by":"publisher","DOI":"10.1097\/00002093-199100510-00005"},{"key":"e_1_2_1_15_1","doi-asserted-by":"publisher","DOI":"10.1007\/BF00687586"},{"key":"e_1_2_1_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(89)91725-X"},{"key":"e_1_2_1_17_1","doi-asserted-by":"publisher","DOI":"10.1038\/349704a0"},{"key":"e_1_2_1_18_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.159.4.524"},{"key":"e_1_2_1_19_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.42.8.1445"},{"key":"e_1_2_1_20_1","volume-title":"Kendrick Cognitive Tests for the Elderly","author":"Kendrick DC","year":"1987"},{"key":"e_1_2_1_21_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/116.2.309"},{"key":"e_1_2_1_22_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.81.11.3443"},{"key":"e_1_2_1_23_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurpsyc.1934.02250040061004"},{"key":"e_1_2_1_24_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.41.1.62"},{"key":"e_1_2_1_25_1","doi-asserted-by":"publisher","DOI":"10.1212\/WNL.34.7.939"},{"key":"e_1_2_1_26_1","volume-title":"Report from the MRC Alzheimer's Disease Workshop","author":"Medical Research Council (UK)","year":"1987"},{"key":"e_1_2_1_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0892-345"},{"key":"e_1_2_1_28_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-340"},{"key":"e_1_2_1_29_1","doi-asserted-by":"publisher","DOI":"10.1002\/ajmg.1320480303"},{"key":"e_1_2_1_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0197-4580(93)90099-W"},{"key":"e_1_2_1_31_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1925564"},{"key":"e_1_2_1_32_1","doi-asserted-by":"publisher","DOI":"10.1016\/0140-6736(91)91612-X"},{"key":"e_1_2_1_33_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1983.04050040033004"},{"key":"e_1_2_1_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0010-9452(78)80049-5"},{"key":"e_1_2_1_35_1","doi-asserted-by":"publisher","DOI":"10.1016\/0888-7543(91)90406-5"},{"key":"e_1_2_1_36_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneur.1990.00530080029006"},{"key":"e_1_2_1_37_1","doi-asserted-by":"publisher","DOI":"10.1192\/bjp.149.6.698"},{"key":"e_1_2_1_38_1","first-page":"847","article-title":"Familial Alzheimer's disease","volume":"47","author":"Sadovnick A","year":"1988","journal-title":"Can J Neurol Sci"},{"key":"e_1_2_1_39_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.3420406"},{"key":"e_1_2_1_40_1","first-page":"563","article-title":"Linkage analysis of familial Alzheimer disease, using chromosome 21 markers","volume":"48","author":"Schellenberg GD","year":"1991","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_41_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1411576"},{"key":"e_1_2_1_42_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0593-10"},{"key":"e_1_2_1_43_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2880399"},{"key":"e_1_2_1_44_1","doi-asserted-by":"publisher","DOI":"10.1038\/347194a0"},{"key":"e_1_2_1_45_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-330"},{"key":"e_1_2_1_46_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/18.12.3672"},{"key":"e_1_2_1_47_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/19.9.2516-a"},{"key":"e_1_2_1_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/0022-510X(70)90063-8"},{"key":"e_1_2_1_49_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1292-335"},{"key":"e_1_2_1_50_1","volume-title":"The Wechsler Adult Intelligence Scale\u2014Revised","author":"Wechsler D","year":"1981"},{"key":"e_1_2_1_51_1","first-page":"204","article-title":"SLINK: A general simulation program for linkage analysis","volume":"47","author":"Weeks D","year":"1990","journal-title":"Am J Hum Genet"},{"key":"e_1_2_1_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/359794a0"},{"key":"e_1_2_1_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0006-291X(91)91011-Z"}],"container-title":["American Journal of Medical Genetics"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1002%2Fajmg.1320600109","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/ajmg.1320600109","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,9,28]],"date-time":"2023-09-28T05:52:51Z","timestamp":1695880371000},"score":1,"resource":{"primary":{"URL":"https:\/\/onlinelibrary.wiley.com\/doi\/10.1002\/ajmg.1320600109"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[1995,2,27]]},"references-count":52,"journal-issue":{"issue":"1","published-print":{"date-parts":[[1995,2,27]]}},"alternative-id":["10.1002\/ajmg.1320600109"],"URL":"https:\/\/doi.org\/10.1002\/ajmg.1320600109","archive":["Portico"],"relation":{},"ISSN":["0148-7299","1096-8628"],"issn-type":[{"value":"0148-7299","type":"print"},{"value":"1096-8628","type":"electronic"}],"subject":[],"published":{"date-parts":[[1995,2,27]]}}}