Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan

Bakhit, Yousuf; Ibrahim, Mohamed O.; Tesson, Christelle; Elhassan, Ali A.; Ahmed, Mohamed Anwer; Alebeed, Mohamed A.; Mohamedelrasheed, Salma; Omar, Mawia A.; Abubaker, Rayan; Eltom, Khalid; Shaheen, Mutaz T.; Ibrahim, Yousuf A.; Almak, Murad E.; Ali, Hiba A.; Abugrain, Ahmed A.; Almahal, Mohamed A.; MohamedSharif, Abubaker A.; Tahir, Mohamed Y.; Malik, Sawazen; Abdelrahman, Hazim Eldirdiri; Khidir, Reem J.; Mohamed, Malaz Tarig AbdAlla; Abdalla, A. A.; Elsayed, Liena; Lesage, Suzanne; Corvol, Jean‐Christophe; Seidi, Osheik; Wüllner, Ullrich

doi:10.1016/j.parkreldis.2023.105401

Cited by 4 publications

(3 citation statements)

References 12 publications

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“…There is increasing consensus that PD is a neurodegenerative disorder with heterogeneous motor and non-motor features [28][29][30][31] . According to previous literature, the heterogeneity of clinical manifestations was associated with age 56,66 , sex 56,66 , life styles 28,67,68 , genetic variations 32,38,44,69 , β-amyloid deposition 70 , tau accumulation 70,71 , varied pathological spread of synucleinopathy 28,70 and diverse degenerative thresholds 28,72 . Genetic variations play an essential role in the modifications of clinical phenotypes of PD patients.…”

Section: The Effects Of Bckdk Rs14235 On Motor Decline Of Pd Patientsmentioning

confidence: 99%

“…Genetic variations play an essential role in the modifications of clinical phenotypes of PD patients. Particularly, numerous mutated genes in PD, such as GBA 36,38,39 , LRRK2 24,40,41 , PRKN 42,43 , PINK1 43,44 , SNCA 41,45 have been demonstrated to significantly shape the clinical heterogeneity of familial PD patients. Motor symptoms of PD patients, on the other hand, were also influenced by genetic variations.…”

Section: The Effects Of Bckdk Rs14235 On Motor Decline Of Pd Patientsmentioning

confidence: 99%

“…Previous studies suggest that genetic variations modify age at onset 32,33 , influence motor progression [34][35][36] , and alter the frequency of a variety of nonmotor symptoms [37][38][39] . Specifically, a multitude of mutated genes, such as GBA 36,38,39 , LRRK2 24,40,41 , PRKN 42,43 , PINK1 43,44 , SNCA 41,45 have been proven to alter the diverse range of symptoms experienced by individuals with familial PD. Therefore, genetic variations significantly contributed to the clinical heterogeneity of PD patients.…”

Section: Introductionmentioning

confidence: 99%

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BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease

Chen

et al. 2023

Preprint

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Background A multitude of genetic variants confer a risk of Parkinson's disease (PD), however, whether these risk variants affected the motor symptoms of PD patients remain largely elusive. The objective of this study is to investigate the effects of BCKDK rs14235 (G > A), a risk variant associated with PD risk, on the motor manifestations and brain networks of PD patients. Methods PD patients (n = 146) receiving magnetic resonance imaging from Parkinson's Progression Markers Initiative (PPMI) database were investigated. The effects of BCKDK rs14235 on the motor manifestations and brain networks of PD patients were systematically evaluated. Results BCKDK rs14235 A allele was associated with milder motor symptoms in PD patients. BCKDK rs14235 significantly modified the topology of brain structural and functional network. The assortativity in structural network was negatively associated with rigidity in PD while the shortest path length of right pallidum was positively associated with Unified Parkinson's Disease Rating Scale part III (UPDRS-III) scores. The mediation analysis suggested that assortativity in structural network mediated the effects of BCKDK rs14235 on rigidity and the shortest path length of right pallidum mediated the effects of BCKDK rs14235 on UPDRS-III scores. Conclusions BCKDK rs14235 significantly shaped the motor impairment and network topology of PD patients. Differential network metrics mediated the effects of BCKDK rs14235 on rigidity and UPDRS-III scores of PD patients. Future studies were required to identify the molecular mechanisms underlying the effects of BCKDK rs14235 on motor impairment and brain network metrics of PD patients.

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Section: The Effects Of Bckdk Rs14235 On Motor Decline Of Pd Patientsmentioning

confidence: 99%

Section: The Effects Of Bckdk Rs14235 On Motor Decline Of Pd Patientsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease

Chen

et al. 2023

Preprint

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Consanguinity and willingness to perform premarital genetic screening in Sudan

Elhadi,

Alrawa,

Alfadul

et al. 2023

Eur J Hum Genet

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Consanguineous marriage is prevalent in certain world regions due to cultural, economic, and social reasons. However, it can lead to negative consequences including an increased risk of genetic disorders in offspring. Premarital genetic screening (PMGS) is an important tool to identify and manage these risks before marriage. This study aimed to assess the magnitude of consanguineous marriage, knowledge of genetic diseases and PMGS, and attitudes and willingness to perform PMGS in Sudan. A national household survey was conducted using a multistage sampling technique, with a sample size of 2272 participants. Data were collected from December 2022 to March 2023 using an interviewer-administered questionnaire. A significant proportion of respondents (364/850, 42.8%) were married to consanguineal partners, with various types of relatedness. Moreover, 32.1% (242/755) of single respondents were planning to marry a close relative, signifying the likely persistence of consanguineous marriages in Sudan. The level of knowledge regarding genetic diseases and PMGS was relatively low in many states of Sudan, indicating the need for increased awareness interventions. A significant number of participants (85.2%) agreed that premarital screening is effective in reducing genetic diseases, whereas 71.2% supported the introduction of a mandatory PMGS program. Excluding married participants, 82.3% (1265/1537) of respondents were willing to perform PMGS, if implemented. These findings reflect the public positive attitude towards introducing the PMGS program and policies in Sudan and underscore the importance of addressing the knowledge gap of PMGS before such a potential implementation.

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Next-generation sequencing and bioinformatics in rare movement disorders

Zech,

Winkelmann

2024

Nat Rev Neurol

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Intrafamilial and interfamilial heterogeneity of PINK1-associated Parkinson's disease in Sudan

Cited by 4 publications

References 12 publications

BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease

BCKDKrs14235 A allele is associated with milder motor impairment and altered network topology in Parkinson’s disease

Consanguinity and willingness to perform premarital genetic screening in Sudan

Next-generation sequencing and bioinformatics in rare movement disorders

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