title: Infantile neuroaxonal dystrophy caused by uniparental disomy.
abstract: Infantile neuroaxonal dystrophy (INAD) is a rare autosomal recessive neurodegenerative disorder caused by mutations in the phospholipase A2 group 6 (Pla2G6) gene. Affected individuals usually present between the ages of 6 months and 2 years with rapid cognitive and motor regression and axial hypotonia. Gait disturbance, limb spasticity, cerebellar signs, and optic atrophy are other common features associated with INAD. Although magnetic resonance imaging (MRI) can sometimes contribute towards the diagnosis, the confirmation of INAD is by Pla2G6 gene analysis. In this case report, we describe the first individual (female) with INAD due to a combination of uniparental heterodisomy and isodisomy; we discuss the possible underlying mechanism and highlight the importance of parental carrier testing in accurately predicting the recurrence risk in these families. We also confirm the recent report of hypertrophy of the clava (also known as the 'gracile tubercle') as a useful MRI sign in INAD.
authors.affiliation: Department of Clinical Genetics, Leicester Royal Infirmary, University Hospitals Leicester, UK; Department of Cancer Studies & Molecular Medicine, University of Leicester, Leicester, UK; Department of Clinical Genetics, Oxford University Hospitals NHS Trust, Oxford, UK.
authors.forename: Joyce
authors.initials: J
authors.lastname: Solomons
authors.forename: Oliver
authors.initials: O
authors.lastname: Ridgway
authors.forename: Carol
authors.initials: C
authors.lastname: Hardy
authors.forename: Manju A
authors.initials: MA
authors.lastname: Kurian
authors.forename: Manju
authors.initials: M
authors.lastname: Kurian
authors.forename: Sandeep
authors.initials: S
authors.lastname: Jayawant
authors.forename: Sarah
authors.initials: S
authors.lastname: Hughes
authors.forename: Pieter
authors.initials: P
authors.lastname: Pretorius
authors.forename: Andrea H
authors.initials: AH
authors.lastname: Németh
mesh_terms: D005260:Female; D054522:Group VI Phospholipases A2 / Q000235:genetics; D006801:Humans; D007223:Infant; D008279:Magnetic Resonance Imaging; D019150:Neuroaxonal Dystrophies / Q000235:genetics*; D024182:Uniparental Disomy / Q000235:genetics / Q000503:physiopathology*
chemical_list: D054522:Group VI Phospholipases A2; C516475:PLA2G6 protein, human