Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients
- PMID: 16688749
- DOI: 10.1002/ajmg.a.31244
Genotype-phenotype correlations in mapped split hand foot malformation (SHFM) patients
Abstract
Split hand foot malformation (SHFM) also known as central ray deficiency, ectrodactyly and cleft hand/foot, is one of the most complex of limb malformations. SHFM can occur as an isolated malformation or in association with other malformations, as in the ectrodactyly-ectodermal dysplasia-clefting (EEC) syndrome and other autosomal dominant conditions with long bone involvement, all showing variable expressivity and reduced penetrance. The deficiency in SHFM patients can also be accompanied by other distal limb anomalies including polydactyly and/or syndactyly. This variability causes the phenotypic classification of SHFM to be far from straightforward and genetic heterogeneity, with at least five loci identified to date, further complicates management of affected patients and their families. Although genotypic-phenotypic correlations have been proposed at the molecular level for SHFM4 patients who have mutations in the P63 gene, phenotypic correlations at the chromosomal level have not been thoroughly documented. Using descriptive epidemiology, Chi square and discriminant function analyses, our laboratory has identified phenotypic patterns associated with the mapped genetic SHFM loci. These findings can assist in classification, provide insight into responsible developmental genes and assist in directing mapping efforts and targeted genetic testing, resulting in more accurate information for family members in the clinical setting. Comparison with relevant animal models is discussed.
(c) 2006 Wiley-Liss, Inc.
Similar articles
-
Pathogenesis of split-hand/split-foot malformation.Hum Mol Genet. 2003 Apr 1;12 Spec No 1:R51-60. doi: 10.1093/hmg/ddg090. Hum Mol Genet. 2003. PMID: 12668597 Review.
-
p63 Gene mutations in eec syndrome, limb-mammary syndrome, and isolated split hand-split foot malformation suggest a genotype-phenotype correlation.Am J Hum Genet. 2001 Sep;69(3):481-92. doi: 10.1086/323123. Epub 2001 Jul 17. Am J Hum Genet. 2001. PMID: 11462173 Free PMC article.
-
Split-hand/split-foot malformation is caused by mutations in the p63 gene on 3q27.Am J Hum Genet. 2000 Jul;67(1):59-66. doi: 10.1086/302972. Epub 2000 Jun 5. Am J Hum Genet. 2000. PMID: 10839977 Free PMC article.
-
Discrepancies in upper and lower limb patterning in split hand foot malformation.Clin Genet. 2005 Nov;68(5):408-23. doi: 10.1111/j.1399-0004.2005.00511.x. Clin Genet. 2005. PMID: 16207208
-
Split-hand/foot malformation - molecular cause and implications in genetic counseling.J Appl Genet. 2014 Feb;55(1):105-15. doi: 10.1007/s13353-013-0178-5. Epub 2013 Oct 27. J Appl Genet. 2014. PMID: 24163146 Free PMC article. Review.
Cited by
-
A new locus for split hand/foot malformation with long bone deficiency (SHFLD) at 2q14.2 identified from a chromosome translocation.Hum Genet. 2007 Sep;122(2):191-9. doi: 10.1007/s00439-007-0390-7. Epub 2007 Jun 14. Hum Genet. 2007. PMID: 17569090
-
Deletions of exons with regulatory activity at the DYNC1I1 locus are associated with split-hand/split-foot malformation: array CGH screening of 134 unrelated families.Orphanet J Rare Dis. 2014 Jul 29;9:108. doi: 10.1186/s13023-014-0108-6. Orphanet J Rare Dis. 2014. PMID: 25231166 Free PMC article.
-
Genome-wide profiling of p63 DNA-binding sites identifies an element that regulates gene expression during limb development in the 7q21 SHFM1 locus.PLoS Genet. 2010 Aug 19;6(8):e1001065. doi: 10.1371/journal.pgen.1001065. PLoS Genet. 2010. PMID: 20808887 Free PMC article.
-
The molecular genetics of human appendicular skeleton.Mol Genet Genomics. 2022 Sep;297(5):1195-1214. doi: 10.1007/s00438-022-01930-1. Epub 2022 Jul 30. Mol Genet Genomics. 2022. PMID: 35907958
-
A novel description of a syndrome consisting of 7q21.3 deletion including DYNC1I1 with preserved DLX5/6 without ectrodactyly: a case report.J Med Case Rep. 2016 Jun 13;10(1):156. doi: 10.1186/s13256-016-0921-8. J Med Case Rep. 2016. PMID: 27291887 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Molecular Biology Databases
Miscellaneous
