Prodromal manifestations of Parkinson´s disease in a high-risk population: 22q11.2 microdeletion syndrome

Project Title

Partner Organisations

Facultad de Medicina Clínica Alemana Universidad del Desarrollo

Internal ID

1171014

Principal Investigator

REPETTO LISBOA, MARIA GABRIELA

Type

basic research

Status

TERMINADO

Start Date

2017

Investigators

REBOLLEDO JARAMILLO, BORIS EDUARDO

Publications

Now showing 1 - 10 of 15

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Genetic contributors to risk of schizophrenia in the presence of a 22q11.2 deletion
(2020)
Isabelle Cleynen
;
Worrawat Engchuan
;
Matthew S. Hestand
;
Tracy Heung
;
Aaron M. Holleman
2Scopus© Citations 99
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Variance of IQ is partially dependent on deletion type among 1,427 22q11.2 deletion syndrome subjects
(2018)
Yingjie Zhao
;
Tingwei Guo
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Ania Fiksinski
;
Elemi Breetvelt
;
Donna M. McDonald-McGinn
12Scopus© Citations 38
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Using common genetic variation to examine phenotypic expression and risk prediction in 22q11.2 deletion syndrome
(2020)
Robert W. Davies
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Ania M. Fiksinski
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Elemi J. Breetvelt
;
Nigel M. Williams
;
Stephen R. Hooper
8Scopus© Citations 109
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Somatic Mosaicism for Paternal Uniparental Disomy of 11p15.5 Region in Adrenal and Liver Tissues in a Newborn with Atypical Beckwith–Wiedemann Syndrome
(2019)
Abraham Urzua
;
Sofia Burattini
;
Constanza Pinochet
;
BENAVIDES GONZALEZ, FELIPE ORLANDO
;
REPETTO LISBOA, MARIA GABRIELA
<jats:title>Abstract</jats:title><jats:p>Beckwith–Wiedemann syndrome (BWS) is characterized by overgrowth and increased risk of embryonic tumors. It results from alterations in genes controlled by imprinting centers H19DMR (Imprinting Center [IC] 1) and KvDMR (IC2). Strategies for diagnostic confirmation include methylation analysis and CDKN1C sequencing. We present a newborn with placentomegaly, hyperinsulinism and adrenal cytomegaly, but no typical external features of BWS. The patient had normal genetic studies in blood. However, adrenal and liver tissues showed hypermethylation of IC1 and hypomethylation of IC2. Microsatellite analysis confirmed mosaic paternal uniparental disomy. This study demonstrates the importance of analyzing additional tissues to reduce underdiagnosis of somatic mosaicism in BWS.</jats:p>
6
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Association between phenotype and deletion size in 22q11.2 microdeletion syndrome: systematic review and meta-analysis
(2019)
M. Fernanda Rozas
;
BENAVIDES GONZALEZ, FELIPE ORLANDO
;
Luis León
;
REPETTO LISBOA, MARIA GABRIELA
Scopus© Citations 25 2
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Contribution of Mitochondrial DNA Heteroplasmy to the Congenital Cardiac and Palatal Phenotypic Variability in Maternally Transmitted 22q11.2 Deletion Syndrome
(2021)
REBOLLEDO JARAMILLO, BORIS EDUARDO
;
Maria Gabriela Obregon
;
Victoria Huckstadt
;
Abel Gomez
;
REPETTO LISBOA, MARIA GABRIELA
<jats:p>Congenital heart disease (CHD) and palatal anomalies (PA), are among the most common characteristics of 22q11.2 deletion syndrome (22q11.2DS), but they show incomplete penetrance, suggesting the presence of additional factors. The 22q11.2 deleted region contains nuclear encoded mitochondrial genes, and since mitochondrial function is critical during development, we hypothesized that changes in the mitochondrial DNA (mtDNA) could be involved in the intrafamilial variability of CHD and PA in cases of maternally inherited 22q11.2DS. To investigate this, we studied the transmission of heteroplasmic mtDNA alleles in seventeen phenotypically concordant and discordant mother-offspring 22q11.2DS pairs. We sequenced their mtDNA and identified 26 heteroplasmic variants at >1% frequency, representing 18 transmissions. The median allele frequency change between a mother and her child was twice as much, with a wider distribution range, in PA discordant pairs, p-value = 0.039 (permutation test, 11 concordant vs. 7 discordant variants), but not in CHD discordant pairs, p-value = 0.441 (9 vs. 9). Only the variant m.9507T>C was considered to be pathogenic, but it was unrelated to the structural phenotypes. Our study is novel, yet our results are not consistent with mtDNA variation contributing to PA or CHD in 22q11.2DS. Larger cohorts and additional factors should be considered moving forward.</jats:p>
1Scopus© Citations 2
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Analysis of REM sleep without atonia in 22q11.2 deletion syndrome determined by domiciliary polysomnography: a cross sectional study
(2021)
Jorge Mauro
;
Mario Diaz
;
Teresa Córdova
;
Katiuska Villanueva
;
Tania Cáceres
<jats:title>Abstract</jats:title> <jats:sec> <jats:title>Study Objectives</jats:title> <jats:p>Our aim is to evaluate the presence of REM sleep without atonia (RWA), the objective hallmark of REM sleep Behaviour Disorder (RBD), as prodromal marker of Parkinson’s disease (PD), in an adult cohort of 22q11.2 deletion syndrome (22qDS).</jats:p> </jats:sec> <jats:sec> <jats:title>Methods</jats:title> <jats:p>Sleep quality was assessed by means of Pittsburgh quality scale index (PSQI), and RBD symptoms by means of RBD questionnaire-Hong-Kong (RBDQ-HK). Attended domiciliary video-Polysomnography (v-PSG) were performed in 26 adults (18–51 years, 14 females) 22qDS patients. Electromyogram during REM sleep was analyzed by means of SINBAR procedure at 3-second time resolution (miniepochs).</jats:p> </jats:sec> <jats:sec> <jats:title>Results</jats:title> <jats:p>An overall poor sleep quality was observed in the cohort and high RBDQ-HK score in 7 of the 26 patients, two additional patients with positive dream enactment reported by close relatives had low score of RBDQ-HK. Nevertheless, SINBAR RWA scores were lower than cut-off threshold for RWA (mean 5.5%, range 0–12.2%). TST and the percentage of light sleep (N1) were increased, with preserved proportions of N2 and N3. Participants reported poor quality of sleep (mean PSQI &gt; 5), with prolonged sleep latency in the v-PSG. No subjects exhibit evident dream enactment episodes during recording sessions.</jats:p> </jats:sec> <jats:sec> <jats:title>Conclusions</jats:title> <jats:p>RWA was absent in the studied cohort of 22qDS adult volunteers according to validated polysomnographic criteria. High RBDQ-HK scores do not correlate with v-PSG results among 22qDS individuals.</jats:p> </jats:sec>
2Scopus© Citations 6
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Sleep architecture in 22q11.2 microdeletion syndrome patients: polysomnographic study of prodromal signs of Parkinson's Disease and obstructive sleep apnea
(2019)
A. Ocampo-Garcés
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M. Diaz
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K. Villanueva
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T. Córdova
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J. Mauro
2
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Pharmacogenetics in Psychiatry: Perceived Value and Opinions in a Chilean Sample of Practitioners
(2021)
UNDURRAGA FOURCADE, JUAN PABLO
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Ignacio Bórquez-Infante
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Nicolás A. Crossley
;
Miguel L. Prieto
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REPETTO LISBOA, MARIA GABRIELA
<jats:p>Use of pharmacogenetics (PGx) testing to guide clinical decisions is growing in developed countries. Published guidelines for gene–drug pair analysis are available for prescriptions in psychiatry, but information on their utilization, barriers, and health outcomes in Latin America is limited. As a result, this work aimed at exploring current use, opinions, and perceived obstacles on PGx testing among psychiatrists in Chile, via an online, anonymous survey. Among 123 respondents (5.9% of registered psychiatrists in the country), 16.3% reported ever requesting a PGx test. The vast majority (95%) of tests were ordered by clinicians practicing in the Metropolitan Region of Santiago. Having more than 20 years in practice was positively associated with prior use of PGx (p 0.02, OR 3.74 (1.19–11.80)), while working in the public health system was negatively associated (OR 0.30 (0.10–0.83)). Perceived barriers to local implementation included insufficient evidence of clinical utility, limited clinicians’ knowledge on PGx and on test availability, and health systems’ issues, such as costs and reimbursement. Despite the recognition of these barriers, 80% of respondents asserted that it is likely that they will incorporate PGx tests in their practice in the next five years. Given these results, we propose next steps to facilitate implementation such as further research in health outcomes and clinical utility of known and novel clinically actionable variants, growth in local sequencing capabilities, education of clinicians, incorporation of clinical decision support tools, and economic evaluations, all in local context.</jats:p>
1Scopus© Citations 10
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Systems Analysis of the 22q11.2 Microdeletion Syndrome Converges on a Mitochondrial Interactome Necessary for Synapse Function and Behavior
(2019)
Avanti Gokhale
;
Cortnie Hartwig
;
Amanda A. H. Freeman
;
Julia L. Bassell
;
Stephanie A. Zlatic
1Scopus© Citations 48

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