Early-onset Parkinson disease leading to diagnosis of 22q11.2 deletion syndrome

Pollard, Rebecca; Hannan, Markus; Tanabe, Jody; Berman, Brian D.

doi:10.1016/j.parkreldis.2016.01.027

Cited by 10 publications

(11 citation statements)

References 5 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This report, despite highlighting a strong epidemiological evidence, it does not provide a genetic investigation of PD-related genes apart from the 22q11.2 mutation. Moreover previous studies analyzing a few patients, report only very few or no genetic analysis related to PD [ 8 , 9 ].…”

Section: Introductionmentioning

confidence: 99%

Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson’s Disease

Gambardella

Ferese

Scala

et al. 2018

Parkinson's Disease

View full text Add to dashboard Cite

Deletion at 22q11.2 responsible for Di George syndrome (DGs) is a risk factor for early-onset Parkinson's disease (EOPD). To date, all patients reported with 22q11.2 deletions and parkinsonian features are negative for a family history of PD, and possible mutations in PD-related genes were not properly evaluated. The goal of this paper was to identify variants in PD genes that could contribute, together with 22q11.2 del, to the onset of parkinsonian features in patients affected by Di George syndrome. To this aim, sequencing analysis of 4800 genes including 17 PD-related genes was performed in a patient affected by DGs and EOPD. The analysis identified mutation p.Gly399Ser in OMI/HTRA2 (PARK13). To date, the mechanism that links DGs with parkinsonian features is poorly understood. The identification of a mutation in a PARK gene suggests that variants in PD-related genes, or in genes still not associated with PD, could contribute, together with deletion at 22q11.2, to the EOPD in patients affected by DGs. Further genetic analyses in a large number of patients are strongly required to understand this mechanism and to establish the pathogenetic role of p.Gly399Ser in OMI/HTRA2.

show abstract

Section: Introductionmentioning

confidence: 99%

Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson’s Disease

Gambardella

Ferese

Scala

et al. 2018

Parkinson's Disease

View full text Add to dashboard Cite

show abstract

“…The findings confirmed the presence of the neurodegenerative process typical for PD and ruled out that all Parkinsonian signs and symptoms were solely induced by neuroleptic treatment for the psychiatric disease manifestations. Case reports and small case series on six additional patients have been published since [45–49]. …”

Section: New Genes For Recessive and X-linked Pd Or Parkinsonismmentioning

confidence: 99%

“…Investigation for 22q11.2 deletions was suggested in the diagnostic workup of patients with early-onset PD who have congenital palatal or cardiac defects, recurrent infections or other signs of immune deficiency, late developmental milestones, or marked psychiatric comorbidity [49]. It has been pointed out that early detection of 22q11.2 deletions might be beneficial for timely recognition and treatment of manifestations such as hypocalcemia, abnormal thyroid or parathyroid function, abnormal magnesium levels, or cardiac abnormalities [49].…”

Section: New Genes For Recessive and X-linked Pd Or Parkinsonismmentioning

confidence: 99%

See 1 more Smart Citation

New Genes Causing Hereditary Parkinson’s Disease or Parkinsonism

Puschmann

2017

Curr Neurol Neurosci Rep

View full text Add to dashboard Cite

Purpose of ReviewThis article reviews genes where putative or confirmed pathogenic mutations causing Parkinson’s disease or Parkinsonism have been identified since 2012, and summarizes the clinical and pathological picture of the associated disease subtypes.Recent FindingsNewly reported genes for dominant Parkinson’s disease are DNAJC13, CHCHD2, and TMEM230. However, the evidence for a disease-causing role is not conclusive, and further genetic and functional studies are warranted. RIC3 mutations have been reported from one family but not yet encountered in other patients. New genes for autosomal recessive disease include SYNJ1, DNAJC6, VPS13C, and PTRHD1. Deletions of a region on chromosome 22 (22q11.2del) are also associated with early-onset PD, but the mode of inheritance and the underlying causative gene remain unclear. PODXL mutations were reported in autosomal recessive PD, but their roles remain to be confirmed. Mutations in RAB39B cause an X-linked Parkinsonian disorder. SummaryMutations in the new dominant PD genes have generally been found in medium- to late-onset Parkinson’s disease. Many mutations in the new recessive and X-chromosomal genes cause severe atypical juvenile Parkinsonism, but less devastating mutations in these genes may cause PD.

show abstract

“…Another important neurological manifestation in 22q11.2DS is parkinsonism. Although the association between this genetic syndrome and parkinsonian features was first observed in 1998,34 few case reports and case series have been published so far, describing the early onset of symptoms in subjects with neither a family history of parkinsonism nor gene mutations commonly associated with early-onset Parkinson’s disease (PD) 35–43. Asymmetric clinical signs, disease course and response to treatment (L-dopa and dopamine agonists) in 22q11.2DS are all similar to those in PD.…”

Section: Introductionmentioning

confidence: 99%

Myoclonic epilepsy, parkinsonism, schizophrenia and left-handedness as common neuropsychiatric features in 22q11.2 deletion syndrome

et al. 2019

View full text Add to dashboard Cite

Background22q11.2 deletion syndrome (22q11.2DS) is considered as the genetic model of schizophrenia. However, its polymorphic nature has led researchers to further investigate its neuropsychiatric manifestations.MethodsWe enrolled 56 adults (38 men, 18 women) diagnosed with 22q11.2DS. All subjects were evaluated by a multidisciplinary team. The neuropsychiatric features were investigated by means of clinical and neurophysiological evaluation (video-EEG).ResultsThirty per cent of our patients were left-handed. Fifty-eight per cent had a low IQ, and 22 of 56 subjects had psychotic disorders (13 of 22 with schizophrenia). Eighteen patients reported at least one seizure in their lifetime, and ten were diagnosed with epilepsy; among them, seven had genetic generalised epilepsy (GGE), and five of seven showed features suggestive of juvenile myoclonic epilepsy (JME). Video-EEG recordings revealed generalised epileptiform abnormalities in 24 of 56 cases. Besides, only one patient with epilepsy had a cardiac malformation. Lastly, 31 of 56 subjects presented with parkinsonism, 16 of whom were taking neuroleptics. None of the 15 patients with parkinsonism not related to neuroleptic therapy was diagnosed with epilepsy, compared with 6 of those taking antipsychotics.Conclusions22q11.2DS is characterised by left-handedness and neuropsychiatric features such as cognitive impairment, schizophrenia, epilepsy and parkinsonism. GGE, mostly the JME phenotype, is the predominant epilepsy type. The significant association between 22q11.2DS and parkinsonian features confirms these patients’ genetic susceptibility to parkinsonism. Despite the lack of any conclusive evidence, our study suggests a possible relationship between the analysed clinical variables: (1) an inverse correlation between low IQ/psychosis/epilepsy and major cardiac diseases; (2) a direct association between psychosis and both mental delay and epilepsy; and (3) an inverse correlation between parkinsonism and epilepsy.

show abstract

Early-onset Parkinson disease leading to diagnosis of 22q11.2 deletion syndrome

Cited by 10 publications

References 5 publications

Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson’s Disease

Mitochondrial Serine Protease HTRA2 p.G399S in a Female with Di George Syndrome and Parkinson’s Disease

New Genes Causing Hereditary Parkinson’s Disease or Parkinsonism

Myoclonic epilepsy, parkinsonism, schizophrenia and left-handedness as common neuropsychiatric features in 22q11.2 deletion syndrome

Contact Info

Product

Resources

About