Multiplex ligation-dependent probe amplification (MLPA) analysis is an effective tool for the detection of novel intragenic PLA2G6 mutations: implications for molecular diagnosis.
Phospholipase associated neurodegeneration (PLAN) comprises a heterogeneous group of autosomal recessive neurological disorders caused by mutations in the PLA2G6 gene. Direct gene sequencing detects approximately 85% mutations in infantile neuroaxonal dystrophy. We report the novel use of multiplex ligation-dependent probe amplification (MLPA) analysis to detect novel PLA2G6 duplications and deletions. The identification of such copy number variants (CNVs) expands the PLAN mutation spectrum and may account for up to 12.5% of PLA2G6 mutations. MLPA should thus be employed to detect CNVs of PLA2G6 in patients who show clinical features of PLAN but in whom both disease-causing mutations cannot be identified on routine sequencing.
Crompton
Danielle
D
West Midlands Regional Genetic Service, Birmingham Women's Hospital, Metchley Park Lane, Birmingham, UK.
Rehal
Pauline K
PK
MacPherson
Lesley
L
Foster
Katharine
K
Lunt
Peter
P
Hughes
Imelda
I
Brady
Angela F
AF
Pike
Michael G
MG
De Gressi
Susanna
S
Morgan
Neil V
NV
Hardy
Carol
C
Smith
Matthew
M
MacDonald
Fiona
F
Maher
Eamonn R
ER
Kurian
Manju A
MA
D001483:Base Sequence; D001921:Brain / Q000473:pathology; D002675:Child, Preschool; D003241:Consanguinity; D017353:Gene Deletion; D020440:Gene Duplication; D054522:Group VI Phospholipases A2 / Q000235:genetics*; D020271:Heredodegenerative Disorders, Nervous System / Q000175:diagnosis / Q000235:genetics; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D008297:Male; D008969:Molecular Sequence Data; D009154:Mutation; D021141:Nucleic Acid Amplification Techniques / Q000379:methods*; D057089:Pathology, Molecular
D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human