Molecular Investigation of Human Split-Hand/Foot
Malformation (SHFM)
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Principal Investigator: |
Charles E.
Schwartz, PhD, Director of Research
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864-941-8140, 1-800-939-1920 (toll free)
864-388-1703 (fax) |
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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 Cindy Skinner, RN, sample coordinator (1-800-939-1920, cindy@ggc.org)
before obtaining and shipping samples to discuss each case individually
and to obtain information, consent forms, shipping payment codes and
customs letters.
All samples should be shipped overnight to:
J.C. Self Research Institute
Greenwood
Genetic Center
113 Gregor Mendel Circle
Greenwood, SC 29646 |
