FIGURE 6.

Pedigree of the PD/LRRK2 p.Asn1437His Polish Family; only generation IV was available for analysis, WES was performed to IV-2 (proband), mutation confirmation by Sanger sequencing was performed for proband’s cousins IV-3 I IV-6. *Indicates that the person was examined. Proband (IV-2) was a 63-year-old female with an 11-year history of PD. The first symptom was asymmetric left upper limb rigidity. After 2 years of disease levodopa treatment was initiated with good response. In neuropsychological examination only mild cognitive impairment was noted. The MRI was normal. When she was 59, she had deep brain stimulation electrodes (DBS) implanted to subthalamic nucleus (STN) with good response. Her cousin IV-3 was a 61-year-old male. The first symptom was right hand rigidity when 55 years old. Six months later levodopa treatment was implemented. He is currently still on a very low dose (300 mg total) of levodopa with good response. The youngest one (IV-6) developed symptoms of PD when he was 49. He presented left upper and later lower limb rigidity with subsequent left hand rest tremor. Three years after symptom onset levodopa treatment was initiated with good response. In the 5th year of the disease, the patient developed on-off fluctuations. He was treated with STN DBS when 57 years old. After the surgery he developed severe dysarthria and psychotic symptoms. However, after the dopamine agonist withdrawal and introduction of quetiapine treatment, the psychotic symptoms disappeared. He is now 64 years old, and the main symptoms are hypokinetic dysarthria with palilalia and echolalia. He is also suffering from severe gait disturbances with postural instability. He has also developed urinary incontinency. All were carriers of heterozygous pathogenic variant in the LRRK2 gene (NM_198578.3; GRCh38) c.[4309A > C];[-] causing missense mutation – p.[(Asn1437His)];[(-)].