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PMID: 7825574 Published · ppublish English Comparative Study Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

The human homologue of the Drosophila melanogaster flightless-I gene (flil) maps within the Smith-Magenis microdeletion critical region in 17p11.2.

American journal of human genetics ·Vol. 56 ·No. 1 ·1995-01-00 ·Pages 175-82

Chen KS, Gunaratne PH, Hoheisel JD, Young IG, Miklos GL, Greenberg F, Shaffer LG, Campbell HD, Lupski JR

Abstract

The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-deletion syndrome associated with a proximal deletion of the short arm of chromosome 17 in band p11.2. The spectrum of clinical findings includes short stature, brachydactyly, developmental delay, dysmorphic features, sleep disturbances, and behavioral problems. The complex phenotypic features suggest deletion of several contiguous genes. However, to date, no protein-encoding gene has been mapped to the SMS critical region. Recently, the Drosophila melanogaster flightless-I gene, fliI, and the homologous human cDNA have been isolated. Mutations in fliI result in loss of flight ability and, when severe, cause lethality due to incomplete cellularization with subsequent abnormal gastrulation. Here, we demonstrate that the human homologue (FLI) maps within the SMS critical region. Genomic cosmids were used as probes for FISH, which localized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mapping further localized this gene to the SMS critical region. Southern blot analysis of somatic-cell hybrids and/or FISH analysis of lymphoblastoid cell lines from 12 SMS patients demonstrates the deletion of one copy of FLI in all SMS patients analyzed.

Related Genes
CMT1 FLI PMP22 fliI
MeSH Terms
Animals Cell Line, Transformed Chromosome Mapping Chromosomes, Human, Pair 17 Cosmids Cricetinae Drosophila melanogaster/genetics Dwarfism/genetics Gelsolin Gene Deletion Genes Genes, Insect Humans Hybrid Cells In Situ Hybridization, Fluorescence Intellectual Disability/genetics Lymphocytes/ultrastructure Mice Microfilament Proteins Morphogenesis/genetics Proteins/genetics Receptors, Cytoplasmic and Nuclear Syndrome Trans-Activators
Chemicals
FLII protein, human Gelsolin Microfilament Proteins Proteins Receptors, Cytoplasmic and Nuclear Trans-Activators
Authors & Affiliations
9 authors, click to expand affiliations / ORCID
Chen K S
Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, TX 77030-3498.
Gunaratne P H
Hoheisel J D
Young I G
Miklos G L
Greenberg F
Shaffer L G
Campbell H D
Lupski J R
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
Published
1995-01-00
Pages
175-82
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1801336
Subset
IM
Grants
NCRR NIH HHS · MOI RR-00188 · United States
External Links
PubMed source PMC Full Text View journal details
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