Ks. Chen et al., THE HUMAN HOMOLOG OF THE DROSOPHILA-MELANOGASTER FLIGHTLESS-I GENE (FLII) MAPS WITHIN THE SMITH-MAGENIS MICRODELETION CRITICAL REGION IN 17P11.2, American journal of human genetics, 56(1), 1995, pp. 175-182
The Smith-Magenis syndrome (SMS) appears to be a contiguous-gene-delet
ion syndrome associated with a proximal deletion of the short arm of c
hromosome 17 in band p11.2. The spectrum of clinical findings includes
short stature, brachydactyly, developmental delay, dysmorphic feature
s, sleep disturbances, and behavioral problems. The complex phenotypic
features suggest deletion of several contiguous genes. However, to da
te, no protein-encoding gene has been mapped to the SMS critical regio
n. 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 in
complete cellularization with subsequent abnormal gastrulation. Here,
we demonstrate that the human homologue (FLI) maps within the SMS crit
ical region. Genomic cosmids were used as probes for FISH, which local
ized this gene to the 17p11.2 region. Somatic-cell hybrid-panel mappin
g further localized this gene to the SMS critical region. Southern blo
t analysis of somatic-cell hybrids and/or FISH analysis of lymphoblast
oid cell lines from 12 SMS patients demonstrates the deletion of one c
opy of FLI in all SMS patients analyzed.