Molecular genetic characterization of a Korean split hand/split foot malformation (SHFM).
Split hand/split foot malformation (SHFM; ectrodactyly) is genetically heterogeneous, with mutations identified at five loci (SHFM1 at 7q21.3, SHFM2 at Xq26, SHFM3 at 10q24, SHFM4 at 3q27 and SHFM5 at 2q31). In this study, we attempted to identify and localize the causative allele of a Korean case of SHFM. Pedigree analysis showed that the Korean SHFM was autosomally dominant and its penetrance was high, indicating that it was not caused by SHFM2. Clinical features were variable, but limited to the four limbs unlike SHFM1, SHFM4 and SHFM5. G-banding and FISH failed to identify any chromosomal abnormalities. We also performed mutation screening by SSCP and DNA sequencing, as well as loss of heterozygosity (LOH) analysis, to exclude the possibility that SHFM4 or SHFM5 were involved; these revealed no mutations in gene p63 and no LOH on 2q31, respectively. It therefore appears that the Korean SHFM may be caused by mutation of SHFM3. In fact, linkage analysis using informative microsatellite markers indicated that SHFM3 was linked to D10S577 with a maximum LOD score of 1.15 at recombination fraction zero. Finally, we identified two novel alleles (191 and 211 bp) of D10S577 that have not been found in Western populations.
Kang
Yoon Sung
YS
Department of Life Science, College of Natural Science, Chung-Ang University, Seoul 156-756, Korea.
Cheong
Hyang-Min
HM
Moon
Youngjoon
Y
Lee
Il Bum
IB
Kim
Sun Mi
SM
Kim
Hwa Su
HS
Jun
Soo Youn
SY
Jung
Sung Kook
SK
Kim
Jin Sook
JS
Choi
Jee Hye
JH
Cho
Hang-Eui
HE
Son
Jin Sook
JS
Min
Na Young
NY
Lee
Kwang-Ho
KH
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D002893:Chromosomes, Human, Pair 3 / Q000235:genetics; D002897:Chromosomes, Human, Pair 7 / Q000235:genetics; D041321:Chromosomes, Human, X / Q000235:genetics; D005532:Foot Deformities, Congenital / Q000235:genetics*; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007723:Korea; D010375:Pedigree; D010641:Phenotype; D018807:Polymorphism, Single-Stranded Conformational