Clinical heterogeneity of PLA2G6-related Parkinsonism: analysis of two Saudi families.
BACKGROUND
Recessive mutations in PLA2G6 have been associated with different neurodegenerative disorders, including infantile neuroaxonal dystrophy, neurodegeneration with brain iron accumulation and more recently, early-onset dystonia parkinsonism.


METHODS
Targeted-next generation sequencing using a custom Neurology panel, containing 758 OMIM-listed genes implicated in neurological disorders, was carried out in two index cases from two different Saudi families displaying early-onset levodopa-responsive Parkinsonism with pyramidal signs and additional clinical features. The detected mutations were verified in the index cases and available family members by direct sequencing.


CONCLUSIONS
We identified a previously described PLA2G6 homozygous p.R741Q mutation in three affected and two asymptomatic individuals from two Saudi families. Our finding reinforces the notion of the broadness of the clinical spectrum of PLA2G6-related neurodegeneration.
Department of Neurosciences, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.
Saeed A
SA
Bohlega
Behavioral Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia. BAl-Mubarak@kfshrc.edu.sa.
Bashayer R
BR
Al-Mubarak
Behavioral Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.
Eman A
EA
Alyemni
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Mohamed
M
Abouelhoda
Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Dorota
D
Monies
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Abeer E
AE
Mustafa
Behavioral Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.
Dania S
DS
Khalil
Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Sara
S
Al Haibi
Department of Neurosciences, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.
Hussam
H
Abou Al-Shaar
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Tariq
T
Faquih
Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Mohamed
M
El-Kalioby
Behavioral Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.
Asma I
AI
Tahir
Behavioral Genetics Unit, Department of Genetics, King Faisal Specialist Hospital and Research Center, P.O Box 3354, Riyadh, 11211, Saudi Arabia.|Saudi Human Genome Project, King Abdulaziz City for Science and Technology, Riyadh, Saudi Arabia.
Nada A
NA
Al Tassan
D000328:Adult; D005192:Family Health; D005260:Female; D018740:Genetic Heterogeneity; D005838:Genotype; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D006239:Haplotypes; D059014:High-Throughput Nucleotide Sequencing; D006720:Homozygote; D006801:Humans; D008297:Male; D020125:Mutation, Missense; D020734:Parkinsonian Disorders / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D012529:Saudi Arabia
D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human
PLA2G6; Parkinsonism; Saudi patients