Linkage and physical mapping of X-linked lissencephaly/SBH (XLIS): A gene causing neuronal migration defects in human brain

M. Elizabeth Ross, Kristina M. Allen, Anand K. Srivastava, Terry Featherstone, Joseph G. Gleeson, Betsy Hirsch, Brian N. Harding, Eva Andermann, Rabi Abdullah, Michael Berg, Désirée Czapansky-Bielman, Dean J. Flanders, Renzo Guerrini, Jacques Motté, A. Puche Mira, Ingrid Scheffer, Samuel Berkovic, F. Scaravilli, Richard A. King, David H. LedbetterDavid Schlessinger, William B. Dobyns, Christopher A. Walsh

Research output: Contribution to journalArticlepeer-review

Abstract

While disorders of neuronal migration are associated with as much as 25% of recurrent childhood seizures, few of the genes required to establish neuronal position in cerebral cortex are known. Subcortical band heterotopia (SBH) and lissencephaly (LIS), two distinct neuronal migration disorders producing epilepsy and variable cognitive impairment, can be inherited alone or together in a single pedigree. Here we report a new genetic locus, XLIS, mapped by linkage analysis of five families and physical mapping of a balanced X;2 translocation in a girl with LIS. Linkage places the critical region in Xq21-q24, containing the breakpoint that maps to Xq22.3-q23 by high-resolution chromosome analysis. Markers used for somatic cell hybrid and fluorescence in situ hybridization analyses place the XLIS region within a 1 cM interval. These data suggest that SBH and X-linked lissencephaly are caused by mutation of a single gene, XLIS, that the milder SBH phenotype in females results from random X-inactivation (Lyonization), and that cloning of genes from the breakpoint region on X will yield XLIS.

Original languageEnglish
Pages (from-to)555-562
Number of pages8
JournalHuman Molecular Genetics
Volume6
Issue number4
DOIs
Publication statusPublished - Apr 1997

ASJC Scopus subject areas

  • Genetics

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