title: Discontinuous microduplications at chromosome 10q24.31 identified in a Chinese family with split hand and foot malformation.
abstract: BACKGROUND
  Split hand/foot malformation (SHFM) is a congenital disorder characterized by a cleft of the hands and/or feet due to dificiency of central rays. Genomic rearrangement at 10q24 has been found to cause nonsyndromic SHFM (SHFM3).
  
  
  METHODS
  Four patients and fourteen unaffected individuals from a four-generation Chinese pedigree with typical SHFM3 phenotypes were recruited for this study. After informed consent was obtained, genome-wide copy number analysis was performed on all patients and two normal family members using the Affymetrix Cytogenetics Whole-Genome 2.7M Array. The results were then confirmed by real-time quantitative polymerase chain reaction in all available individuals of this pedigree. Candidate genes were further screened for mutation through sequence analyses.
  
  
  RESULTS
  Copy number analysis showed a microduplication at chromosome 10q24.31-q24.32 co-segregating with the SHFM phenotype. Compared to other known genomic duplications for SHFM3, the duplication described here contains two discontinuous DNA fragments. The minimal centromeric duplicated segment of 259 kb involves LBX1, POLL and a disrupted BTRC. The minimal telomeric duplication of 114 kb encompasses DPCD and one part of FBXW4. No coding and splice-site mutations of candidate genes in the region were found.
  
  
  CONCLUSIONS
  Genomic duplications at chromosome 10q24.3, which were identified in the current study, provide further evidence for limb-specific cis-regulatory sequences in this region, highlighting the importance of chromosome 10q24.31-q24.32 in limb development and SHFM pathogenesis.
authors.affiliation: National Center for Birth Defects Monitoring, Chengdu, China. daili@scu.edu.cn
authors.forename: Li
authors.initials: L
authors.lastname: Dai
authors.forename: Ying
authors.initials: Y
authors.lastname: Deng
authors.forename: Nana
authors.initials: N
authors.lastname: Li
authors.forename: Liang
authors.initials: L
authors.lastname: Xie
authors.forename: Meng
authors.initials: M
authors.lastname: Mao
authors.forename: Jun
authors.initials: J
authors.lastname: Zhu
mesh_terms: D044466:Asian People / Q000235:genetics; D002503:Centromere / Q000235:genetics; D002675:Child, Preschool; D058674:Chromosome Duplication; D002879:Chromosomes, Human, Pair 10 / Q000235:genetics*; D056915:DNA Copy Number Variations; D004252:DNA Mutational Analysis; D044783:F-Box Proteins / Q000235:genetics; D005260:Female; D005820:Genetic Testing; D015894:Genome, Human; D055106:Genome-Wide Association Study / Q000379:methods; D018398:Homeodomain Proteins / Q000235:genetics; D006801:Humans; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics*; D008297:Male; D009154:Mutation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D010641:Phenotype; D011506:Proteins / Q000235:genetics; D011859:Radiography; D060888:Real-Time Polymerase Chain Reaction; D012045:Regulatory Sequences, Nucleic Acid; D016615:Telomere / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D044844:beta-Transducin Repeat-Containing Proteins / Q000235:genetics
chemical_list: C471644:BTRC protein, human; C484968:DPCD protein, human; D044783:F-Box Proteins; C120449:FBXW4 protein, human; D018398:Homeodomain Proteins; C542809:LBX1 protein, human; D011506:Proteins; D014157:Transcription Factors; D044844:beta-Transducin Repeat-Containing Proteins