title: An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21.
abstract: Polymicrogyria is a cerebral cortical malformation that is grossly characterized by excessive cortical folding and microscopically characterized by abnormal cortical layering. Although polymicrogyria appears to have one or more genetic causes, no polymicrogyria loci have been identified. Here we describe the clinical and radiographic features of a new genetic form of polymicrogyria and localize the responsible gene. We studied two consanguineous Palestinian pedigrees with an autosomal recessive form of bilateral frontoparietal polymicrogyria (BFPP), using linkage analysis. Five affected children had moderate-to-severe mental retardation, developmental delay, and esotropia, and four of the five affected children developed seizures. Brain magnetic-resonance imaging revealed polymicrogyria that was most prominent in the frontal and parietal lobes but involved other cortical areas as well. A genomewide linkage screen revealed a single locus that was identical by descent in affected children in both families and showed a single disease-associated haplotype, suggesting a common founder mutation. The locus for BFPP maps to chromosome 16q12.2-21, with a minimal interval of 17 cM. For D16S514, the maximal pooled two-point LOD score was 3.98, and the maximal multipoint LOD score was 4.57. This study provides the first genetic evidence that BFPP is an autosomal recessive disorder and serves as a starting point for the identification of the responsible gene.
authors.affiliation: Division of Neurogenetics, Department of Neurology, Beth Israel Deaconess Medical Center and Harvard Medical School, Boston, MA 02115, USA.
authors.forename: Xianhua
authors.initials: X
authors.lastname: Piao
authors.forename: Lina
authors.initials: L
authors.lastname: Basel-Vanagaite
authors.forename: Rachel
authors.initials: R
authors.lastname: Straussberg
authors.forename: P Ellen
authors.initials: PE
authors.lastname: Grant
authors.forename: Elizabeth W
authors.initials: EW
authors.lastname: Pugh
authors.forename: Kim
authors.initials: K
authors.lastname: Doheny
authors.forename: Betty
authors.initials: B
authors.lastname: Doan
authors.forename: Susan E
authors.initials: SE
authors.lastname: Hong
authors.forename: Yin Yao
authors.initials: YY
authors.lastname: Shugart
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Walsh
mesh_terms: D000293:Adolescent; D002648:Child; D002675:Child, Preschool; D002874:Chromosome Mapping; D002885:Chromosomes, Human, Pair 16 / Q000235:genetics*; D003241:Consanguinity; D005260:Female; D005625:Frontal Lobe / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D005808:Genes, Recessive / Q000235:genetics*; D006239:Haplotypes / Q000235:genetics; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D008126:Lod Score; D008279:Magnetic Resonance Imaging; D008297:Male; D009421:Nervous System Malformations / Q000235:genetics* / Q000473:pathology / Q000503:physiopathology; D010154:Pakistan; D010296:Parietal Lobe / Q000002:abnormalities* / Q000473:pathology / Q000503:physiopathology; D010375:Pedigree