TY - JOUR
T1 - Genotype-phenotype analysis of 4q deletion syndrome
T2 - Proposal of a critical region
AU - Strehle, Eugen Matthias
AU - Yu, Linbo
AU - Rosenfeld, Jill A.
AU - Donkervoort, Sandra
AU - Zhou, Yulin
AU - Chen, Tian Jian
AU - Martinez, Jose E.
AU - Fan, Yao Shan
AU - Barbouth, Deborah
AU - Zhu, Hongbo
AU - Vaglio, Alicia
AU - Smith, Rosemarie
AU - Stevens, Cathy A.
AU - Curry, Cynthia J.
AU - Ladda, Roger L.
AU - Fan, Zheng Jane
AU - Fox, Joyce E.
AU - Martin, Judith A.
AU - Abdel-Hamid, Hoda Z.
AU - McCracken, Elizabeth A.
AU - McGillivray, Barbara C.
AU - Masser-Frye, Diane
AU - Huang, Taosheng
PY - 2012/9
Y1 - 2012/9
N2 - 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.
AB - 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.
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U2 - 10.1002/ajmg.a.35502
DO - 10.1002/ajmg.a.35502
M3 - Article
C2 - 22847869
AN - SCOPUS:84865541166
SN - 1552-4825
VL - 158 A
SP - 2139
EP - 2151
JO - American Journal of Medical Genetics, Part A
JF - American Journal of Medical Genetics, Part A
IS - 9
ER -