a single base substitution in exon 6 that generates a 
new 5' splice site that is used exclusively and results 
in an niRNA deleted for 24 bases. 
The search for this novel mutation in patients 
from other areas of the world had been negative. 
During the past year seven unrelated patients from 
four different continents, including South African 
blacks and American blacks, were studied, and six 
different mutations that account for all 14 alleles 
were identified. These include two new splice site 
mutations, two different dinucleotide deletions, 
and one new and one previously reported nonsense 
mutation. The mutations appear to be unique to par- 
ticular geographic areas, and most patients are ho- 
mozygous for the same alleles. 
All of the 1 0 mutations identified worldwide (6 of 
them discovered in Dr. Francke's laboratory) in- 
volve the extracellular domain and are predicted to 
lead to virtual absence of the receptor from the cell 
surface. Missense mutations in the extracellular do- 
main that may lead to abnormal receptor interac- 
tions, or mutations in the intracellular domain that 
may interfere with signal transduction, have not yet 
been identified. It is possible that such mutations 
would result in a milder form of dwarfism. 
Dr. Francke is also Professor of Genetics and 
Pediatrics at the Stanford University School of 
Medicine and Medical Staff member of Lucile 
Salter Packard Children 's Hospital and Stanford 
University Hospital. 
Articles 
Berg, M.A., Guevara -Aguirre, J.G., Rosenbloom, 
A.L., Rosenfeld, R.G., and Francke, U. 1992. Mu- 
tation creating a new donor splice site in the 
growth hormone receptor genes of 37 Ecuador- 
ean patients with Laron syndrome. Hum Muta- 
tion 1:24-34. 
Berkemeier, L.R., Oz^elik, T., Francke, U., and Ro- 
senthal, A. 1992. Human chromosome 19 con- 
tains the neurotrophin-5 gene locus and three re- 
lated genes that may encode novel acidic 
neurotrophins. Somat Cell Mol Genet 18:233- 
245. 
Davidson, J.J., Oz^elik, T., Hamacher, C., Willems, 
P.J., Francke, U., and Kiliman, M.W. 1992. cDNA 
cloning of a liver isoform of the phosphorylase 
kinase a subunit and mapping of the gene to 
Xp22.2-p22.1, the region of human X-linked 
liver glycogenosis. Proc Natl Acad Sci USA 
89:2096-2100. 
Francke, U. 1992. Chromosome banding: methods, 
myths, and misconceptions. Review of Chromo- 
some Banding by A.T. Sumner. Cell 68:1005- 
1006. 
Francke, U., Hsieh, C.-L., Kelly, D., Lai, E., and 
Popko, B. 1992. Induced reciprocal translocation 
in transgenic mice near sites of transgene integra- 
tion. Mamm Genome 3:209-216. 
Giacalone, J. P., and Francke, U. 1992. Common 
sequence motifs at the rearrangement sites of a 
constitutional X/autosome translocation and as- 
sociated deletion. Am J Hum Genet 50:725-74 1 . 
Giacalone, J., Friedes, J., and Francke, U. 1992. A 
novel GC-rich human macrosatellite VNTR in 
Xq24 is differentially methylated on active and 
inactive X chromosomes. Nature Genet 1:137- 
143. 
Jenkins, E.P., Hsieh, C.-L., Milatovich, A., Norming- 
ton, K., Berman, D.M., Francke, U., and Russell, 
D.W. 1991. Characterization and chromosomal 
mapping of human steroid 5a-reductase gene and 
pseudogene and mapping of the mouse homo- 
logue. Genomics 11:1102-1112. 
Kwon, B.S., Chintamaneni, C, Kozak, C.A., Cope- 
land, N.G., Gilbert, D.J. , Jenkins, N., Barton, D., 
Francke, U., Kobayashi, Y., and Kim, K.K. 1991. 
A melanocyte-specific gene, Pmel 17, maps near 
the silver coat color locus on mouse chromosome 
1 0 and is in a syntenic region on human chromo- 
some 12. Proc Natl Acad Sci USA 88:9228- 
9232. 
Lindgren, V., Bryke, C.R., Oz^elik, T., Yang-Feng, 
T.L., and Francke, U. 1992. Phenotypic, cytoge- 
netic, and molecular studies of three patients 
with constitutional deletions of chromosome 5 in 
the region of the gene for familial adenomatous 
polyposis. Am f Hum Genet 50:988-997. 
Marcus, S., Steen, A.-M., Andersson, B., Lambert, B., 
Kristoffersson, U., and Francke, U. 1992. Muta- 
tion analysis and prenatal diagnosis in a Lesch- 
Nyhan family showing non-random X-inactivation 
interfering with carrier detection tests. Human 
Genet 89:395-400. 
Matsuo, M., Nishio, H., Kitoh, Y., Francke, U., and 
Nakamura, H. 1992. Partial deletion of a dystro- 
phin gene leads to exon skipping and to loss of an 
intra-exon hairpin structure from the predicted 
mRNA precursor. Biochem Biophys Res Com- 
mun 182:495-500. 
Milatovich, A., and Francke, U. 1992. Human cy- 
clin Bl gene (CCNBl) assigned to chromosome 5 
(ql3-qter). Somat Cell Mol Genet 18:303-307. 
Milatovich, A., Song, K., Heller, R.A., and Francke, 
U. 1991. Tumor necrosis factor receptor genes, 
TNFRl and TNFR2, on human chromosomes 12 
and 1. Somat Cell Mol Genet 11:519-525. 
Milatovich, A., Travis, A., Grosschedl, R., and 
190 
