Alternative titles; symbols
ORPHA: 1020; DO: 0110043;
Cytogenetic location: 7q36 Genomic coordinates (GRCh38): 7:148,200,001-159,345,973
| Location | Phenotype |
Phenotype MIM number |
Inheritance |
Phenotype mapping key |
|---|---|---|---|---|
| 7q36 | Alzheimer disease-10 | 609636 | Autosomal dominant | 2 |
For a phenotypic description and a discussion of genetic heterogeneity of Alzheimer disease (AD), see 104300.
In an extended multiplex family, ascertained in a population-based study of early-onset AD in the northern Netherlands, Rademakers et al. (2005) obtained conclusive evidence of linkage of AD with a candidate region of 19.7 cM at 7q36. They identified a shared haplotype at 7q36 between the index family and 3 of 6 multiplex AD-affected families from the same geographic region, which was indicative of a founder effect and defined a priority region of 9.3 cM. Mutation analysis of coding exons of 29 candidate genes identified only an exonic silent mutation in the PAXIP1 gene (608254), 38030G-C in the exon 10 genomic sequence, which affected codon 626. It remained to be determined whether PAXIP1 has a functional role in the expression of AD in the index family or whether another mutation at this locus explained the observed linkage and sharing. Association data in a population-based early-onset AD patient-control sample strongly supported the linkage data from the informative index family indicating a novel AD locus at 7q36. The genetic heterogeneity of AD was emphasized. It is noteworthy that another gene in the 7q36 region, NOS3 (163729), has also been associated with Alzheimer disease.
Rademakers, R., Cruts, M., Sleegers, K., Dermaut, B., Theuns, J., Aulchenko, Y., Weckx, S., De Pooter, T., Van den Broeck, M., Corsmit, E., De Rijk, P., Del-Favero, J., van Swieten, J., van Duijn, C. M., Van Broeckhoven, C. Linkage and association studies identify a novel locus for Alzheimer disease at 7q36 in a Dutch population-based sample. Am. J. Hum. Genet. 77: 643-652, 2005. [PubMed: 16175510] [Full Text: https://doi.org/10.1086/491749]