Objective: LRP10 variants have recently been identified in individuals with familial Parkinson’s disease (PD) and dementia with Lewy bodies. We aim to investigate if any of the reported variants are present in 2,409 Chinese Parkinson’s disease patients and controls from Singapore.

Background: A recent study reported by Quadri et al (2018) has identified nine rare, potentially pathogenic LRP10 variants in individuals with familial Parkinson’s disease (PD) and dementia with Lewy bodies. Of interest, the LRP10 1424+5delG splice variant was found in probands of two unrelated Chinese families from Taiwan. The c.1424+5delG variant appears to be specific to East Asians and is extremely rare, found in five heterozygotes out of 8,623 individuals (0.029%) in gnomAD data. It is unclear if this variant is associated with PD risk in the Chinese population.

Method: We sequenced all coding exons of LRP10 in 1,072 Chinese PD patients (age at onset 64.9 ± 10.4 years, 88 with onset below 50 years; age at sample collection 69.0 ± 9.6 years; 611 males; 101 (9.4%) familial PD and 971 (90.6%) sporadic PD) and 1,337 healthy Chinese controls (57.3 ± 9.5 years; 688 males) from Singapore.

Results: We did not find any of the nine reported variants in the 2,409 samples we sequenced, including the splice variant c.1424+5delG that was reported in Chinese families from Taiwan. The lack of observation of the reported LRP10 variants was not due to insufficient coverage in our samples, as all the nine variant positions had high mean coverage of 40x (range 2x-138x) in all our samples. In particular, the c.1424+5delG position had a mean coverage of 22x, with 93.9% of 2,409 samples covered by 10 or more good quality reads (base quality ≥ 10, mapping quality ≥ 20).

Conclusion: We conclude that the c.1424+5delG is a very uncommon cause of PD in the Chinese population. Confirmation in additional families segregating this variant will be helpful, although this may be challenging given the variable penetrance and age of onset of PD in these carriers. Moreover, additional clinical data on carriers of c.1424+5delG and other mutations in LRP10 is needed to lend more weight to the pathogenicity of this variant.

References: Quadri M, Mandemakers W, Grochowska MM, et al. LRP10 genetic variants in familial Parkinson’s disease and dementia with Lewy bodies: a genome-wide linkage and sequencing study. The Lancet Neurology 2018; 17(7): 597-608.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/lrp10-variants-and-parkinsons-disease-in-the-chinese-population/