Genotype-phenotype analysis of 4q deletion syndrome: Proposal of a critical region

Eugen Matthias Strehle, Linbo Yu, Jill A. Rosenfeld, Sandra Donkervoort, Yulin Zhou, Tian Jian Chen, Jose E. Martinez, Yao Shan Fan, Deborah Barbouth, Hongbo Zhu, Alicia Vaglio, Rosemarie Smith, Cathy A. Stevens, Cynthia J. Curry, Roger L. Ladda, Zheng Jane Fan, Joyce E. Fox, Judith A. Martin, Hoda Z. Abdel-Hamid, Elizabeth A. McCrackenBarbara C. McGillivray, Diane Masser-Frye, Taosheng Huang

Research output: Contribution to journalArticlepeer-review

50 Scopus citations


Chromosome 4q deletion syndrome (4q- syndrome) is a rare condition, with an estimated incidence of 1 in 100,000. Although variable, the clinical spectrum commonly includes craniofacial, developmental, digital, skeletal, and cardiac involvement. Data on the genotype-phenotype correlation within the 4q arm are limited. We present detailed clinical and genetic information by array CGH on 20 patients with 4q deletions. We identified a patient who has a ∼465kb deletion (186,770,069-187,234,800, hg18 coordinates) in 4q35.1 with all clinical features for 4q deletion syndrome except for developmental delay, suggesting that this is a critical region for this condition and a specific gene responsible for orofacial clefts and congenital heart defects resides in this region. Since the patients with terminal deletions all had cleft palate, our results provide further evidence that a gene associated with clefts is located on the terminal segment of 4q. By comparing and contrasting our patients' genetic information and clinical features, we found significant genotype-phenotype correlations at a single gene level linking specific phenotypes to individual genes. Based on these data, we constructed a hypothetical partial phenotype-genotype map for chromosome 4q which includes BMP3, SEC31A, MAPK10, SPARCL1, DMP1, IBSP, PKD2, GRID2, PITX2, NEUROG2, ANK2, FGF2, HAND2, and DUX4 genes.

Original languageEnglish (US)
Pages (from-to)2139-2151
Number of pages13
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number9
StatePublished - Sep 2012

All Science Journal Classification (ASJC) codes

  • Genetics
  • Genetics(clinical)


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