John P. Hussman Institute for Human Genomics (HIHG)
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In July 2022, Dr. Martinez presented the results of our first preliminary analyses at the Alzheimer’s Association International Conference in San Diego, California.
An update of these analyses was presented by Dr. Nuytemans in October 2022 at the American Society of Human Genetics meeting in Los Angeles, CA.
Please see the results listed below.
Overall demographic and clinical description of the participants in the study
As this is the first time we are presenting our analyses in samples of this study group, we presented general information on participants’ countries of origin, the age at which FTD was first seen in the participants and their general clinical symptoms.
The study group presented contained 92 FTD participants, of which 58 identified as Hispanic, 25 as non-Hispanic white and 9 as Black or African American.
65% of the participants enrolled in Miami are Caribbean; i.e. Puerto Rico or Cuba.
When comparing the genetic ancestries present in the participants to African, European or Amerindian individuals, we saw a great variety of genetic admixture (= combination of ancestries in one individual).
71% of the participants enrolled in Miami have a diagnosis of bvFTD, 6% were diagnosed with just PPA and the remaining 23% had symptoms of both bvFTD and PPA at time of enrollment in the study
All patients had similar ages when first symptoms were seen; 61.5years in Non-Hispanic whites and 58.9years in Hispanic individuals.
We did not see any global clinical differences between the different population groups in the study.
Genomic analyses in known FTD genes
The current known genes linked to FTD are mostly identified in individuals of European ancestry. As Hispanics and African Americans both have some European ancestry as well (mixed with African and Native American) we would expect to see some FTD participants to have variants in the known European genes as well, but also new variants in new disease genes. This first analysis was limited to screening the known European genes.
We did not find any rare mutations in the two genes that are more commonly mutated in European FTD patients (C9orf72 and GRN)
We identified one Hispanic participant with a variant in TBK1 (p.S679Kfs3). This variant was not reported in any other FTD patient before but is predicted to have similar effects as other known mutations in TBK1.
We identified one rare variant in CHMP2B (p.S287N) in 30% of our Black/African American participants. This variant is more common on the African background (regardless of disease status) so we would need to do more research to determine whether FTD patients are more likely to have this variant than healthy individuals.
Genomic analyses in known Alzheimer’s Disease (AD) genes
Mutations in AD genes have been reported in FTD patients as well. We screened the 3 best known genes for AD in our study group.
We identified three individuals (two Hispanic, one black/African American) with presumed pathogenic mutations in ‘presenilin 1’. These variants are likely coming from their European ancestry.
Please see the videos below from the recent presentation "Hot topics in Brain Health: How to build a better brain” symposium organized by the Comprehensive Center for Brain Health in Boca Raton, FL.
