A second autosomal split hand/split foot locus maps to chromosome 10q24-q25.
Ectrodactyly (split hand/split foot malformation, SHSF) is a human limb malformation characterized by absent central digital rays, deep median cleft, and syndactyly of remaining digits. The disorder is genetically heterogeneous, with at least two loci thus far determined: an autosomal locus at 7q21 designated SHFM1 and an X-linked locus at Xq26 designated SHFM2. Cytogenetic analysis of sporadic SHSF patients and linkage studies in extended pedigrees both suggest more than one autosomal locus exists. We report a novel SHSF locus suggested by a stillborn infant with ectrodactyly and other malformations who inherited an unbalanced translocation resulting in monosomy 4p15.1-4pter and trisomy for 10q25.2-qter. To investigate 10q25 as a possible split hand/split foot locus, microsatellite markers spanning 52 cM of 10q were utilized for linkage analysis of a large autosomal dominant SHSF pedigree in which the region encompassing SHFM1 previously was excluded as containing the causative mutation. The marker D10S583 was fully informative in the family, giving a maximum LOD score of 4.21 at recombination theta = 0.00. Recombination haplotypes define the 9 cM region between D10S541 and D10S574 as inclusive for this second autosomal SHSF locus, for which we propose the designation SHFM3.
Nunes
M E
ME
Department of Pediatrics, University of Washington, Seattle 98195, USA.
Schutt
G
G
Kapur
R P
RP
Luthardt
F
F
Kukolich
M
M
Byers
P
P
Evans
J P
JP
D000015:Abnormalities, Multiple / Q000235:genetics*; D002869:Chromosome Aberrations / Q000235:genetics*; D025063:Chromosome Disorders; D002874:Chromosome Mapping; D002879:Chromosomes, Human, Pair 10; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics*; D008040:Genetic Linkage; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D010375:Pedigree