Molecular Investigation of Human Split-Hand/Foot Malformation (SHFM)

Principal Investigator
Charles E. Schwartz, PhD, Director of Research
Phone: 864.941.8140
Toll Free: 800.939.1920
Fax: 864.388.1703

SHFM is a congenital limb malformation that affects 1 in 8,000-25,000 individuals. It occurs as an isolated malformation or in association with other skeletal or non-skeletal anomalies and is often inherited as an autosomal dominant trait with marked variability in expression and reduced penetrance. Like other congenital limb deficiencies, SHFM in its many forms causes significant disability. However, its causes remain largely unknown. Thus far, 5 loci for human SHFM have been mapped: SHFM1 (chromosome 7q21-22), SHFM2 (Xq26), SHFM3 (10q24), SHFM4 (3q27), and SHFM5 (2q31). To date, only the gene p63 (also called TP63) on chromosome 3 has been identified as a cause of SHFM. Recently, rearrangements involving the SHFM3 locus on chromosome 10q24 have also been associated with SHFM. The goals of this research are to identify additional genes and elucidate the molecular and developmental mechanisms causing SHFM in humans.

The types of SHFM under investigation are

  • Isolated SHFM
  • SHFM with other skeletal anomalies, including:
    • long bone deficiency (SHFLD)
    • triphalangeal thumb (triphalangeal thumb-brachyectrodactyly syndrome)
  • Syndromic forms of SHFM, including:
    • Ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome
    • SHFM with sensorineural hearing loss
    • SHFM with microphthalmia, colobomas, or other eye defects
    • Microcephaly-microphthalmia-ectrodactyly-prognathism syndrome
    • Any other syndrome with SHFM as a feature

The methodologies and testing utilized in the study include:

  • Marker analysis to localize SHFM genes in families or test for linkage to known SHFM loci
  • SSCP and sequence analysis of p63 and other candidate SHFM genes
  • Pulsed field gel electrophoresis (PFGE) and Southern analysis
  • Real-time quantitative PCR and RT-PCR
  • High-resolution chromosome analysis and FISH

Sample Submission

Sample Requirements:

Proband: Lymphoblast cell line – yellow top, ACD solution A tube – minimum of 5cc whole blood DNA isolation – purple top, EDTA tube – minimum of 3 cc whole blood Chromosome analysis – green top, sodium heparin tube – minimum of 2 cc whole blood

Parents: Lymphoblast cell line – yellow top, ACD solution A tube – minimum of 5cc whole blood DNA isolation – purple top, EDTA tube – minimum of 3 cc whole blood

Familial cases: Please contact the lab for sample requirements on members of extended family

Other Requirements: Detailed clinical information, including pedigree, photos, and x-rays of affected persons is requested to facilitate testing and permit study of genotype-phenotype correlations.

Shipping: Please contact Melanie May, sample coordinator (1-800-939-1920, This email address is being protected from spambots. You need JavaScript enabled to view it. ) before obtaining and shipping samples to discuss each case individually and to obtain information, consent forms, shipping payment codes and customs letters.

Research Sample Forms

Research Sample Form to be submitted with all molecular research samples.

Metabolomics Request Form to be submitted with all metabolic profiling samples.


Ship all samples overnight to:

J.C. Self Research Institute
Greenwood Genetic Center
113 Gregor Mendel Circle
Greenwood, SC 29646