Identification of GBA mutations among neurodegenerative disease patients from eastern India.

Introduction: GBA mutations have been reported in PD, PDD and DLB - but not associated with cognitive impairment for example in PSP, AD or MSA. However, frequencies of GBA mutations are ethnicity dependent. The present study aims to identify commonly reported GBA mutations (mostly from Asia), among eastern Indian patients with neurodegenerative disorders.
Methods: The patient cohort consisting of 198 classical PD cases, 136 PD cases with cognitive impairment, 184 cases with Parkinson Plus syndrome, 46 AD and 241 unrelated controls, from eastern India. Subjects were analyzed for IVS2 + 1A > G, p.Arg120Trp, p.His255Gln, p.Arg257Gln, p.Glu326Lys, p.Asn370Ser, p.Asp409His, p.Leu444Pro, & RecNciI by PCR-RFLP techniques and confirmed by Sanger sequencing method.
Results: We have identified only p.Leu444Pro variant among nine cases; three PDD, one DLB, two PD, two PSP and one AD patients in heterozygous condition. The highest frequency for p.Leu444Pro variant was found among PDD subgroup (3.95 %, P = 0.0134). An overall significant overrepresentation of positive family history (P = 0.000049), impaired recent memory (P = 0.0123) was observed among p.Leu444Pro carriers. Further, subgroup analysis for PD, PD-MCI and PDD, revealed statistically significant higher frequency of early age at onset (P = 0.0455), positive family history (P = 0.0025), higher UPDRS III score (off state) (P = 0.006), advanced H&Y stage (P = 0.045) and anxious behaviour (P = 0.0124) among p.Leu444Pro positive patients.
Conclusion: The p.Leu444Pro mutation of GBA was found in patients with PD, PDD, DLB, PSP and AD. An Overall higher frequency of positive family history and impaired recent memory are significantly associated with for p.Leu444Pro carriers from eastern India. Our study also ascertains contribution of p.Leu444Pro to an earlier onset of PD, PD-MCI and PDD, higher UPDRS III score (off state) against positive family history background. Furthermore, taking into consideration other Indian studies, we can conclude that p.Leu444Pro mutation plays a limited role in PD and other neurodegenerative disorders.
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