TY - JOUR
T1 - An autosomal recessive form of bilateral frontoparietal polymicrogyria maps to chromosome 16q12.2-21
AU - Piao, Xianhua
AU - Basel-Vanagaite, Lina
AU - Straussberg, Rachel
AU - Grant, P. Ellen
AU - Pugh, Elizabeth W.
AU - Doheny, Kim
AU - Doan, Betty
AU - Hong, Susan E.
AU - Shugart, Yin Yao
AU - Walsh, Christopher A.
N1 - Funding Information:
We thank the families who kindly consented to join the study; Dr. L. Kornreich and Professor C. Legum, for invaluable help with sample collection and MRI analysis; Timothy Cherry, for helping to determine marker-allele frequencies; Adria Bodell, for coordinating patient studies; and other members of the Walsh lab, for their help. This work was supported by National Institutes of Health program grant HD07466 (to X.P.), by National Institute of Neurological Disorders and Stroke grant R01 NS 35129 (to C.A.W.), and by the March of Dimes. The Center for Inherited Disease Research is fully funded through a federal contract (N01-HG-65403) from the National Institutes of Health to Johns Hopkins University.
PY - 2002/4
Y1 - 2002/4
N2 - 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.
AB - 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.
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U2 - 10.1086/339552
DO - 10.1086/339552
M3 - Article
C2 - 11845408
AN - SCOPUS:18344389160
SN - 0002-9297
VL - 70
SP - 1028
EP - 1033
JO - American journal of human genetics
JF - American journal of human genetics
IS - 4
ER -