Consistent chromosome abnormalities identify novel polymicrogyria loci in 1p36.3, 2p16.1-p23.1, 4q21.21-q22.1, 6q26-q27, and 21q2.
Polymicrogyria is a malformation of cortical development characterized by loss of the normal gyral pattern, which is replaced by many small and infolded gyri separated by shallow, partly fused sulci, and loss of middle cortical layers. The pathogenesis is unknown, yet emerging data supports the existence of several loci in the human genome. We report on the clinical and brain imaging features, and results of cytogenetic and molecular genetic studies in 29 patients with polymicrogyria associated with structural chromosome rearrangements. Our data map new polymicrogyria loci in chromosomes 1p36.3, 2p16.1-p23, 4q21.21-q22.1, 6q26-q27, and 21q21.3-q22.1, and possible loci in 1q44 and 18p as well. Most and possibly all of these loci demonstrate incomplete penetrance and variable expressivity. We anticipate that these data will serve as the basis for ongoing efforts to identify the causal genes located in these regions.
Dobyns
William B
WB
Department of Human Genetics, The University of Chicago, Chicago, Illinois 60637, USA. wbd@bsd.uchicago.edu
Mirzaa
Ghayda
G
Christian
Susan L
SL
Petras
Kristin
K
Roseberry
Jessica
J
Clark
Gary D
GD
Curry
Cynthia J R
CJ
McDonald-McGinn
Donna
D
Medne
Livija
L
Zackai
Elaine
E
Parsons
Julie
J
Zand
Dina J
DJ
Hisama
Fuki M
FM
Walsh
Christopher A
CA
Leventer
Richard J
RJ
Martin
Christa L
CL
Gajecka
Marzena
M
Shaffer
Lisa G
LG
D000015:Abnormalities, Multiple / Q000235:genetics / Q000473:pathology; D000293:Adolescent; D000328:Adult; D000782:Aneuploidy; D001921:Brain / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002869:Chromosome Aberrations; D019457:Chromosome Breakage; D002872:Chromosome Deletion; D022202:Chromosomes, Artificial, Bacterial / Q000235:genetics; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics; D002896:Chromosomes, Human, Pair 6 / Q000235:genetics; D005260:Female; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D007231:Infant, Newborn; D007621:Karyotyping; D008297:Male; D054220:Malformations of Cortical Development / Q000235:genetics* / Q000473:pathology; D010641:Phenotype; D014178:Translocation, Genetic