<i>C9orf72</i> expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort

Tan, Yi Jayne; Yong, Alisa C.W.; Foo, Jia Nee; Lian, Michelle Mulan; Lim, Weng Khong; Dominguez, Jacqueline C.; Fong, Zhi Hui; Narasimhalu, Kaavya; Chiew, Hui Jin; Ng, Kok Pin; Ting, Simon; Kandiah, Nagaendran; Ng, Adeline Su Lyn

doi:10.1002/acn3.51744

Cited by 2 publications

(1 citation statement)

References 72 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…4A, Table S17). In agreement with current known epidemiological studies, we observed that pathogenic alleles in 11,[37][38][39][40] . Given that the initial ancestry assignments for our cohort were based on genome-wide data, we performed local ancestry analysis to check for admixture in these individuals, confirming that the expanded repeat alleles segregated on haplotypes of African and South Asian ancestry (Methods).…”

Section: Red Mutation Frequency In Different Populationssupporting

confidence: 93%

Increased frequency of repeat expansion mutations across different populations

Ibañez,

Jadhav,

Zanovello

et al. 2023

Preprint

View full text Add to dashboard Cite

Repeat expansion disorders (REDs) are a devastating group of predominantly neurological diseases. Together they are common, affecting 1 in 3,000 people worldwide with population-specific differences. However, prevalence estimates of REDs are hampered by heterogeneous clinical presentation, variable geographic distributions, and technological limitations leading to under-ascertainment. Here, leveraging whole genome sequencing data from 82,176 individuals from different populations we found an overall carrier frequency of REDs of 1 in 340 individuals. Modelling disease prevalence using genetic data, age at onset and survival, we show that REDs are up to 3-fold more prevalent than currently reported figures. While some REDs are population-specific, e.g. Huntington disease type 2, most REDs are represented in all broad genetic ancestries, including Africans and Asians, challenging the notion that some REDs are found only in European populations. These results have worldwide implications for local and global health communities in the diagnosis and management of REDs both at local and global levels.

show abstract

Section: Red Mutation Frequency In Different Populationssupporting

confidence: 93%

Increased frequency of repeat expansion mutations across different populations

Ibañez,

Jadhav,

Zanovello

et al. 2023

Preprint

View full text Add to dashboard Cite

show abstract

Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia

Ng,

Tan,

Tan

et al. 2024

Movement Disorders

View full text Add to dashboard Cite

BackgroundProgressive supranuclear palsy (PSP) is largely a sporadic disease with few reported familial cases. Genome‐wide association studies (GWAS) in sporadic PSP in Caucasian populations have identified MAPT as the most commonly associated genetic risk locus with the strongest effect size. At present there are limited data on genetic factors associated with PSP in Asian populations.ObjectivesOur goal was to investigate the genetic factors associated with PSP in Southeast Asian PSP patients.MethodsNext‐generation sequencing (whole‐exome, whole‐genome and targeted sequencing) was performed in two Asian cohorts, comprising 177 PSP patients.ResultsWe identified 17 pathogenic or likely pathogenic variants in 16 PSP patients (9%), eight of which were novel. The most common relevant genetic variants identified were in MAPT, GBA1, OPTN, SYNJ1, and SQSTM1. Other variants detected were in TBK1, PRNP, and ABCA7—genes that have been implicated in other neurodegenerative diseases. Eighteen patients had a positive family history, of whom two carried pathogenic MAPT variants, and one carried a likely pathogenic GBA1 variant. None of the patients had expanded repeats in C9orf72. Furthermore, we found 16 different variants of uncertain significance in 21 PSP patients in PSEN2, ABCA7, SMPD1, MAPT, ATP13A2, OPTN, SQSTM1, CYLD, and BSN.ConclusionsThe genetic findings in our PSP cohorts appear to be somewhat distinct from those in Western populations, and also suggest an overlap of the genetic architecture between PSP and other neurodegenerative diseases. Further functional studies and validation in independent Asian cohorts will be useful for improving our understanding of PSP genetics and guiding genetic screening strategies in these populations. © 2024 International Parkinson and Movement Disorder Society.

show abstract

C9orf72 expansions are the most common cause of genetic frontotemporal dementia in a Southeast Asian cohort

Cited by 2 publications

References 72 publications

Increased frequency of repeat expansion mutations across different populations

Increased frequency of repeat expansion mutations across different populations

Identification of Genetic Variants in Progressive Supranuclear Palsy in Southeast Asia

Contact Info

Product

Resources

About