Isolation of a Miller–Dicker lissencephaly gene containing G protein β-subunit-like repeats

  title={Isolation of a Miller–Dicker lissencephaly gene containing G protein $\beta$-subunit-like repeats},
  author={Orly Reiner and Romeo Carrozzo and Ying Shen and Manfred S. Wehnert and Fabrizia Faustinella and William B. Dobyns and Charles Thomas Caskey and David H. Ledbetter},
LISSENCEPHALY (agyria-pachygyria) is a human brain malformation manifested by a smooth cerebral surface and abnormal neuronal migration1,2. Identification of the gene(s) involved in this disorder would facilitate molecular dissection of normal events in brain development3. Type 1 lissencephaly occurs either as an isolated abnormality or in association with dysmorphic facial appearance in patients with Miller–Dieker syndrome4,5. About 15% of patients with isolated lissencephaly and more than 90… 

Point mutations and an intragenic deletion in LIS1, the lissencephaly causative gene in isolated lissencephaly sequence and Miller-Dieker syndrome.

LIS1 is confirmed as the gene responsible for classical lissencephaly in ILS and MDS and band-shifts for three patients, each involving a different coding exon, which were not observed in their respective parental DNAs are confirmed.

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

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, supporting the original concept MDS as a contiguous gene deletion syndrome.

Genomic organization of the murine Miller-Dieker/lissencephaly region: conservation of linkage with the human region.

The results demonstrate that the MDS region is conserved between human and mouse and suggests that the mouse can be used to model microdeletions that occur in ILS and MDS.

The location and type of mutation predict malformation severity in isolated lissencephaly caused by abnormalities within the LIS1 gene.

Using a spectrum of ILS patients, it is confirmed the importance of specific WD40 repeats and a putative microtubule-binding domain for PAFAH1B1 function and hypothesize that the greater lissencephaly severity seen in Miller-Dieker syndrome may be secondary to the loss of another cortical development gene in the deletion of 17p13.3.

Genotype-phenotype correlations for the type 1 lissencephaly of eight Tunisian children Journal of Clinical Images and Medical Case Reports

The data confirm the individuality and originality of type 1 lissencephaly on both the phenotypic and the genetic lev -els and spotlight the usefulness of developing approaches and methods for detecting a large number of known causative gene mutations.

Differences in the gyral pattern distinguish chromosome 17–linked and X-linked lissencephaly

Genotype-phenotype analysis in children with lissencephaly associated with mutations of different genes found consistent differences in the gyral patterns, with the malformation more severe posteriorly in individuals with LIS1 mutations and more severe anteriorly in Individuals with XLIS mutations.

Lissencephaly. A human brain malformation associated with deletion of the LIS1 gene located at chromosome 17p13.

Deletions of the lissencephaly critical region in chromosome 17p13.3, including LIS1, appear to be the most frequent cause of classical lissENCEphaly.

Large spectrum of lissencephaly and pachygyria phenotypes resulting from de novo missense mutations in tubulin alpha 1A (TUBA1A)

Retrospective examination of MR images suggests that patients with TUBA1A mutations share not only cortical dysgenesis, but also cerebellar, hippocampal, corpus callosum, and brainstem abnormalities, and highlights the importance of the MTs/DCX complex in the neuronal migration process.



Microdeletions of chromosome 17p13 as a cause of isolated lissencephaly.

Investigation of the possibility that some ILS patients have smaller deletions in this chromosomal region found in situ hybridization proved to be the most rapid and sensitive method of deletion detection.

Molecular dissection of a contiguous gene syndrome: frequent submicroscopic deletions, evolutionarily conserved sequences, and a hypomethylated "island" in the Miller-Dieker chromosome region.

A hypomethylated island and evolutionarily conserved sequences were identified within this 100-kb region, indications of the presence of one or more expressed sequences potentially involved in the pathophysiology of this disorder.

Clinical and molecular diagnosis of Miller-Dieker syndrome.

The demonstration of cytogenetic or molecular deletions in 21 of 25 MDS probands proves that deletion of a "critical region" comprising two or more genetic loci within band 17p13.3 is the cause of the MDS phenotype.

Detection of deletions and cryptic translocations in Miller-Dieker syndrome by in situ hybridization.

In situ hybridization is an efficient method for deletion detection in Miller-Dieker syndrome and parental studies by FISH on patients demonstrating molecular deletions and a normal karyotype may identify cryptic translocation events, which cannot be detected by other molecular genetic strategies.

Lissencephaly in 2 siblings

This report is based upon 2 consecutive, nontwin siblings, a female and a male, each of whom had additional defects resulting from anomalous development of structures present during the second and third months of gestation, found to have the same anomaly of brain, lissencephaly.

The neurogenetics of lissencephaly.

Comparative analysis of the β transducin family with identification of several new members including PWP1, a nonessential gene of Saccharomyces cerevisiae that is divergently transcribed from NMT1

A systematic and quantitative comparative analysis resulted in classifying all β‐transducin‐like sequences into II nonorthologous families based on specific sequence attributes, however, not allβ‐transduin‐ like sequences are expected to be functionally similar, and quantitative criteria for inferring functional analogies are discussed.

Physical linkage of a guanine nucleotide-binding protein-related gene to the chicken major histocompatibility complex.

Several genes were found closely associated with major histocompatibility class I and class II beta-chain genes in chicken genomic DNA clusters by hybridizing tissue-specific cDNA probes to cosmid clones to clone the homologous sequence H12.3.