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

Stefano Gambardella,Francesco Fabbiano,Stefania Carboni,Simona Scala,Giardina Emiliano,Stefania Zampatti,Francesca Biagioni,Stefano Ruggieri,Francesco Fornai,Diego Centonze,Nicola Modugno,Rosangela Ferese

doi:10.1155/2018/5651435

Abstract

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.

Highlights

Stefano Gambardella,1 Rosangela Ferese,1 Simona Scala,1 Stefania Carboni,2 Francesca Biagioni,1 Giardina Emiliano,2,3 Stefania Zampatti,1,2 Nicola Modugno,1 Francesco Fabbiano,1 Francesco Fornai,1,4 Diego Centonze,1 and Stefano Ruggieri1
All patients reported with 22q11.2 deletions and parkinsonian features are negative for a family history of Parkinson’s disease (PD), and possible mutations in PD-related genes were not properly evaluated. e 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
In an effort to correlate at the molecular level the clinical association between Di George syndrome (DGs) and early-onset Parkinson’s disease (EOPD), in the present study, we report a detailed genetic study carried out by analyzing the clinical exome including 18 PD-related genes in a woman with a clinical diagnosis of DGs confirmed by the presence of a 22q deletion

Summary

Introduction

Stefano Gambardella ,1 Rosangela Ferese, Simona Scala, Stefania Carboni, Francesca Biagioni ,1 Giardina Emiliano, Stefania Zampatti, Nicola Modugno, Francesco Fabbiano, Francesco Fornai ,1,4 Diego Centonze ,1 and Stefano Ruggieri. E 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. E 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. PD typically occurs late in life, but 4% of cases has an onset before the age of 50 [3]

Methods

Findings

Discussion

Conclusion