A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3

Samuel S. Chong, Svetlana D. Pack, Anna V. Roschke, Akira Tanigami, Romeo Carrozzo, Ann C.M. Smith, William B. Dobyns, David H. Ledbetter

Research output: Contribution to journalArticlepeer-review

152 Scopus citations


Miller-Dieker syndrome (MDS) is a multiple malformation syndrome characterized by classical lissencephaly and a characteristic facies. It is associated with visible or submicroscopic deletions within chromosome band 17p13.3. Lissencephaly without facial dysmorphism has also been observed and is referred to as isolated lissencephaly sequence (ILS). Apparently partial and non-overlapping deletions of the 5' or 3' end of a candidate gene LIS1 in one ILS and one MDS patient had suggested that MDS was a single gene disorder, and that LIS1 spans in excess of 400 kb. However, the originally presumed 5' end of LIS1 was found to belong to the 14-3-3ε gene residing more distally on 17p13.3. We have now isolated the correct 5' end of LIS1, constructed a ~ 500 kb genomic contig encompassing LIS1, and estimated its gene extent to be ~ 80 kb. Fluorescence in situ hybridization analysis of an ILS patient with a de novo balanced translocation, as well as analysis of several other key MDS and ILS deletion patients, localizes the lissencephaly critical region within the LIS1 gene. Therefore, LIS1 remains the strongest candidate gene for the lissencephaly phenotype in ILS and MDS. Our analyses also suggest that additional genes distal to LIS1 may be responsible for the facial dysmorphology and other abnormalities seen in MDS but not in ILS patients, supporting our original concept of MDS as a contiguous gene deletion syndrome.

Original languageEnglish (US)
Pages (from-to)147-155
Number of pages9
JournalHuman molecular genetics
Issue number2
StatePublished - Feb 1997


Dive into the research topics of 'A revision of the lissencephaly and Miller-Dieker syndrome critical regions in chromosome 17p13.3'. Together they form a unique fingerprint.

Cite this