PINK1 mutations are the second most common cause of recessive, early-onset Parkinson’s disease (EOPD), of which 15% are cases of juvenile PD. PD is a progressive neurological disease that primarily affects middle-aged and older people. Thus PD patients experiencing pregnancy is uncommon, especially in patients with juvenile PD caused by PINK1 mutations. We are first to report a woman from a Chinese family diagnosed with sporadic juvenile PD and treated with levodopa/benserazide throughout pregnancy.
Whole exome sequencing was performed on this patient, and pedigree verification was performed on her parents. This patient received levodopa/benserazide treatment with regular outpatient follow-up exams.
Whole exome sequencing and Sanger sequencing identified a heterozygous nonsense mutation (c.1474C > T, p.R492X) and a splicing mutation (c.1488 + 1G > A) that were in exon 7 of the PINK1 gene, co-segregating with the PD phenotype and exhibiting an autosomal recessive pattern. With regular outpatient follow-up exams, this patient delivered a healthy boy without complications. Her PD symptoms were stable with the levodopa/benserazide treatment throughout her pregnancy except in the postpartum period.
Our findings further demonstrated the safety of levodopa with dopa-decarboxylase treatment in PINK1-associated juvenile PD during pregnancy.
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A K, Society OWJMdojotMD (1998) Selegiline, pregnancy, and Parkinson's disease. 13:175–176
Asha B, Hansali N, Apoorva P (2010) Successful birth of an IVF baby in a patient with Parkinson’s disease. J Hum Reprod Sci 3:42–43
Ben El Haj R, Regragui W, Tazi-Ahnini R, Skalli A, Bouslam N, Benomar A, Yahyaoui M, Bouhouche A (2016) A Novel Homozygous p.L539F Mutation Identified in PINK1 Gene in a Moroccan Patient with Parkinsonism. Biomed Res Int 2016:3460234
Benbir G, Ertan S, Ozekmekci S (2014) Successful pregnancy and delivery in a patient with Parkinson’s disease under pramipexole treatment. Presse Med 43:83–85
Benito-León J, Bermejo F, Porta-Etessam J (1999) Pregnancy in Parkinson’s disease: a review of the literature and a case report. Mov Disord 14:194
BJ R, RJ M, neurotherapeutics SLJEro (2008) Pregnancy in Parkinson's disease: case report and discussion. 8:1799-1805
Bonifati V, Rohe CF, Breedveld GJ, Fabrizio E, De Mari M, Tassorelli C, Tavella A, Marconi R, Nicholl DJ, Chien HF, Fincati E, Abbruzzese G, Marini P, De Gaetano A, Horstink MW, Maat-Kievit JA, Sampaio C, Antonini A, Stocchi F, Montagna P, Toni V, Guidi M, Dalla Libera A, Tinazzi M, De Pandis F, Fabbrini G, Goldwurm S, de Klein A, Barbosa E, Lopiano L, Martignoni E, Lamberti P, Vanacore N, Meco G, Oostra BA (2005) Early-onset parkinsonism associated with PINK1 mutations: frequency, genotypes, and phenotypes. Neurology 65:87–95
Cook DG, Klawans HL (1985) Levodopa during pregnancy. Clin Neuropharmacol 8:93–95
De Mari M, Zenzola A, Lamberti P (2002) Antiparkinsonian treatment in pregnancy. Mov Disord 17:428–429
Guo JF, Xiao B, Liao B, Zhang XW, Nie LL, Zhang YH, Shen L, Jiang H, Xia K, Pan Q, Yan XX, Tang BS (2008) Mutation analysis of Parkin, PINK1, DJ-1 and ATP13A2 genes in Chinese patients with autosomal recessive early-onset Parkinsonism. Mov Disord 23:2074–2079
Hagell P, Odin P, Vinge E (1998) Pregnancy in Parkinson’s disease: a review of the literature and a case report. Mov Disord 13:34–38
Hatano Y, Li Y, Sato K, Asakawa S, Yamamura Y, Tomiyama H, Yoshino H, Asahina M, Kobayashi S, Hassin-Baer S, Lu CS, Ng AR, Rosales RL, Shimizu N, Toda T, Mizuno Y, Hattori N (2004) Novel PINK1 mutations in early-onset parkinsonism. Ann Neurol 56:424–427
Hughes AJ, Daniel SE, Kilford L, Lees AJ (1992) Accuracy of clinical-diagnosis of idiopathic parkinsons-disease—a clinicopathological study of 100 cases. J Neurol Neurosurg Psychiatry 55:181–184
Kasten M, Hartmann C, Hampf J, Schaake S, Westenberger A, Vollstedt EJ, Balck A, Domingo A, Vulinovic F, Dulovic M, Zorn I, Madoev H, Zehnle H, Lembeck CM, Schawe L, Reginold J, Huang J, Konig IR, Bertram L, Marras C, Lohmann K, Lill CM, Klein C (2018) Genotype-phenotype relations for the parkinson’s disease genes parkin, PINK1, DJ1: MDSGene systematic review. Mov Disord 33:730–741
Li N, Wang L, Zhang J, Tan EK, Li J, Peng J, Duan L, Chen C, Zhou D, He L, Peng R (2020) Whole-exome sequencing in early-onset Parkinson's disease among ethnic Chinese. Neurobiology of aging 90:150 e155–150 e111
LM S, A M, Society WWJMdojotMD (2000) The effect of pregnancy in Parkinson's disease. 15:132-135
Merchant CA, Cohen G, Mytilineou C, DiRocco A, Moros D, Molinari S, Yahr MD (1995) Human transplacental transfer of carbidopa/levodopa. J Neural Trans Parkinson’s Dis Dementia Sect 9:239–242
Mucchiut M, Belgrado E, Cutuli D, Antonini A, Bergonzi P (2004) Pramipexole-treated Parkinson’s disease during pregnancy. Mov Disord 19:1114–1115
Neurology GLJ (1987) Parkinson's disease and pregnancy. 37:1245-1249
Nora J, Nora A, Way GJL (1975) Letter: Cardiovascular maldevelopment associated with maternal exposure to amantadine. 2:607
OS G, neurology LAJAi (1987) Juvenile onset Parkinson's disease. 45:213-216
Peter Hagell PO, Vinge E (1998) Pregnancy in Parkinson s disease A review of the literature and a case report. Movement Dis 13:34–38
R H, K S, T R, neurologica MFJC (1975) Stereotactic treatment of action myoclonus in a case of combined status marmoratus and multiple sclerosis. A contribution to the pathophysiology of basal ganglia with multiple lesions in both the striatum and the substantia nigra. 37:329-356
R S-P, J G-E, M P, S F, HR S, Neurology BSJ (1999) The effect of estrogen replacement on early Parkinson's disease. 52:1417–1421
Routiot T, Lurel S, Denis E, Barbarino-Monnier P (2000) Parkinson’s disease and pregnancy: case report and literature review. J Gynecol Obstet Biol Reprod 29:454–457
Samaranch L, Lorenzo-Betancor O, Arbelo JM, Ferrer I, Lorenzo E, Irigoyen J, Pastor MA, Marrero C, Isla C, Herrera-Henriquez J, Pastor P (2010) PINK1-linked parkinsonism is associated with Lewy body pathology. Brain 133:1128–1142
Scott M, Chowdhury M (2005) Pregnancy in Parkinson’s disease: unique case report and review of the literature. Mov Disord 20:1078–1079
Serikawa T, Shimohata T, Akashi M, Yokoseki A, Tsuchiya M, Hasegawa A, Haino K, Koike R, Takakuwa K, Tanaka K, Tanaka K, Nishizawa M (2011) Successful twin pregnancy in a patient with parkin-associated autosomal recessive juvenile parkinsonism. BMC Neurol 11:72
Xie T, Ho SL, Ramsden D (1999) Characterization and implications of estrogenic down-regulation of human catechol-O-methyltransferase gene transcription. Mol Pharmacol 56:31–38
Zlotnik Y, Giladi N, Hilel A, Shapira Y, Goldstein S, Gurevich T (2014) Levodopa-carbidopa intestinal gel (LCIG) infusion during pregnancy and delivery: first documented case. Parkinsonism Relat Disord 20:1317–1318
The authors are thankful to the patient and her families for their participation in the present study. This study was supported by National Natural Science Foundation of China (81801272), Sichuan Science and Technology Program (2018HH0077), and Post-Doctor Research Project, West China Hospital, Sichuan University (2018HXBH085).
This study was supported by National Natural Science Foundation of China (81801272), Sichuan Science and Technology Program (2018HH0077), and Post-Doctor Research Project, West China Hospital, Sichuan University (2018HXBH085).
Conflicts of interest
The authors declare that they have no conflict of interest.
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Li, Jy., Li, Nn., Wang, L. et al. A compound heterozygous PINK1-associated juvenile Parkinson’s disease with pregnancy in Chinese. J Neurol 268, 2223–2227 (2021). https://doi.org/10.1007/s00415-021-10405-z
- Parkinson’s disease
- Compound heterozygous