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Patient with bilateral periventricular nodular heterotopia and polymicrogyria with apparently balanced reciprocal translocation t(1;6)(p12;p12.2) that interrupts the mannosidase alpha, class 1A, and glutathione S-transferase A2 genes
  1. E P Leeflang1,
  2. S E Marsh1,
  3. E Parrini2,
  4. F Moro2,
  5. D Pilz3,
  6. W B Dobyns4,
  7. R Guerrini5,
  8. J W Wheless6,
  9. J G Gleeson1
  1. 1Department of Neurosciences, University of California at San Diego, La Jolla, California, USA
  2. 2Neurogenetics Laboratory, Istituto di Neuropsichiatria Infantile (INPE), University of Pisa, IRCCS Fondazione Stella Maris, Pisa, Italy
  3. 3Institute for Medical Genetics, University Hospital of Wales, Heath Park, Cardiff, UK
  4. 4Departments of Human Genetics, Neurology, and Pediatrics, University of Chicago, Chicago, USA
  5. 5Neurosciences Unit, Great Ormond Street Hospital for Sick Children and Institute of Child Health, University College London, London, United Kingdom
  6. 6Department of Neurology and Pediatrics, Texas Comprehensive Epilepsy Program, University of Texas-Houston, Houston, Texas, USA
  1. Correspondence to:
 Dr Gleeson
 Department of Neurosciences, MTF 312, University of California, at San Diego, La Jolla, CA 92093-0624, USA;

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Polymicrogyria (PMG) is a cortical development defect that results in an irregular brain surface, with multiple, small, partly fused gyri separated by shallow sulci. The perisylvian form is the most common pattern of PMG seen on magnetic resonance imaging scans of the brain. Bilateral perisylvian PMG (BPP) often is accompanied by mild mental retardation, epilepsy, and pseudobulbar palsy, and this results in problems with expressive speech and feeding.1

Bilateral periventricular nodular heterotopia (BPNH) is a neuronal migration disorder, in which neurons that fail to migrate into the developing cortex remain on the ventricular surface and form nodules that line the lateral ventricles.2 It can be inherited as an X linked dominant trait.3 Female patients with BPNH are of normal intelligence, have seizures, and may have complications in the vascular system, including patent ductus arteriosus and coagulopathy. Few male patients with BPNH have been reported4,5; however, most male fetuses with BPNH are not viable. Male patients with BNPH may present with mental retardation, epilepsy, and other congenital anomalies, including cerebellar hypoplasia and syndactyly. Mutations in filamin A (FLNA, also known as filamin 1, OMIM 300017) on Xq28 were found to be causative for BPNH.6 Many patients with BPNH do not harbor mutations in FLNA,5 which suggests that additional loci can be causative for BPNH. Not enough families, however, have been available for linkage studies to identify other loci.

We present the first reported case of a young male who has PMG and BPNH. The patient has seizures and developmental delay. Cytogenetic analysis showed balanced reciprocal translocations in the child and in his father. The translocation breakpoint was mapped and found to interrupt two genes—mannosidase alpha, class 1A (MAN1A2) and glutathione S-transferase A2 (GSTA2). Deletions of greater than two …

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