title: Genotype-phenotype analysis of 4q deletion syndrome: proposal of a critical region.
abstract: 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 ∼465 kb 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.
authors: Institute of Human Genetics, Newcastle upon Tyne, United Kingdom.
authors: Eugen-Matthias
authors: EM
authors: Strehle
authors: Linbo
authors: L
authors: Yu
authors: Jill A
authors: JA
authors: Rosenfeld
authors: Sandra
authors: S
authors: Donkervoort
authors: Yulin
authors: Y
authors: Zhou
authors: Tian-Jian
authors: TJ
authors: Chen
authors: Jose E
authors: JE
authors: Martinez
authors: Yao-Shan
authors: YS
authors: Fan
authors: Deborah
authors: D
authors: Barbouth
authors: Hongbo
authors: H
authors: Zhu
authors: Alicia
authors: A
authors: Vaglio
authors: Rosemarie
authors: R
authors: Smith
authors: Cathy A
authors: CA
authors: Stevens
authors: Cynthia J
authors: CJ
authors: Curry
authors: Roger L
authors: RL
authors: Ladda
authors: Zheng Jane
authors: ZJ
authors: Fan
authors: Joyce E
authors: JE
authors: Fox
authors: Judith A
authors: JA
authors: Martin
authors: Hoda Z
authors: HZ
authors: Abdel-Hamid
authors: Elizabeth A
authors: EA
authors: McCracken
authors: Barbara C
authors: BC
authors: McGillivray
authors: Diane
authors: D
authors: Masser-Frye
authors: Taosheng
authors: T
authors: Huang
mesh_terms: D002872:Chromosome Deletion; D002894:Chromosomes, Human, Pair 4; D055028:Comparative Genomic Hybridization; D005260:Female; D005838:Genotype; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D010641:Phenotype; D013577:Syndrome