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Marc Cruts, Hubert Backhovens, Sheng-Yue Wang, Geert Van Gassen, Jessie Theuns, Chris De Jonghe, Anita Wehnert, Joke De Voecht, Goedele De Winter, Patrick Cras, Marc Bruyland, Nicole Datson, Jean Weissenbach, Johan T.den Dunnen, Jean-Jaques Martin, Lydia Hendriks, Christine Van Broeckhoven, Molecular genetic analysis of familial early-onset Alzheimer's disease linked to chromosome 14q24.3, Human Molecular Genetics, Volume 4, Issue 12, December 1995, Pages 2363–2371, https://doi.org/10.1093/hmg/4.12.2363
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Abstract
Genetic linkage studies have indicated that chromosome 14q24.3 harbours a major locus for early-onset (onset age <65 years) Alzheimer's disease (AD3). Positional cloning efforts have identified a novel gene S182 or presenilin 1 as the AD3 gene. We have mapped S182 in the AD3 candidate region between D14S277 and D14S284 defined by genetic linkage studies in the two chromosome 14 linked, early-onset AD families AD/A and AD/B. We have shown that S182 is expressed in lymphoblasts and have determined the complete cDNA in both brain and lymphoblasts by RT-PCR sequencing. S182 is alternatively spliced in both brain and lymphoblasts within a putative phosphorylation site located 5′ in the coding region. We identified two novel mutations, Ile143Thr and Gly384Ala located in, respectively, the second transmembrane domain and in the sixth hydrophilic loop of the putative transmembrane structure of S182. As families AD/A and AD/B have a very similar AD phenotype our observation of two mutations in functionally different domains suggest that onset age and severity of AD may not be very helpful predictors of the location of putative S182 mutations.
