title: A 1.6-Mb microdeletion in chromosome 17q22 leads to NOG-related symphalangism spectrum disorder without intellectual disability.
abstract: Microdeletions in chromosome 17q22, where the NOG gene resides, have been reported leading to the NOG-related symphalangism spectrum disorder (NOG-SSD), intellectual disability and other developmental abnormalities. In this study we reported a dominant Chinese Han family segregating with typical NOG-SSD symptoms including proximal symphalangism, conductive hearing loss, amblyopia and strabismus, but not intellectual disability. Sanger sequencing identified no pathogenic mutation in the coding regions of candidate genes NOG, GDF5 and FGF9. SNP genotyping in the genomic region surrounding NOG identified loss of heterozygosity in the affected family members. By array comparative genomic hybridization and quantitative real-time polymerase chain reaction, we identified and mapped the breakpoints of a novel 1.6-Mb microdeletion in chromosome 17q22 that included NOG and twelve other genes. It is the first microdeletion reported in chromosome 17q22 that is associated with NOG-SSD only but not with intellectual disability. Our results may help identifying the dosage sensitive genes for intellectual disability and other developmental abnormalities in chromosome 17q22. Our study also suggested that genomic deletions in chromosome 17q22 should be screened in the NOG-SSD patients in which no pathogenic mutation is identified by conventional sequencing methods.
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China; Department of Otorhinolaryngology-Head and Neck Surgery, Taizhou People's Hospital, Jiangsu Province, China.
authors: Xiuhong
authors: X
authors: Pang
authors: Department of Otolaryngology, Renji hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.
authors: Huajie
authors: H
authors: Luo
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Yongchuan
authors: Y
authors: Chai
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Xiaowen
authors: X
authors: Wang
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Lianhua
authors: L
authors: Sun
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Longxia
authors: L
authors: He
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Penghui
authors: P
authors: Chen
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Hao
authors: H
authors: Wu
authors: Department of Otolaryngology-Head and Neck Surgery, Xinhua Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China; Ear Institute, Shanghai Jiaotong University School of Medicine, Shanghai, China; Shanghai Key Laboratory of Translational Medicine on Ear and Nose Diseases, Shanghai, China.
authors: Tao
authors: T
authors: Yang
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D000328:Adult; D002348:Carpal Bones / Q000002:abnormalities*; D002648:Child; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D055028:Comparative Genomic Hybridization / Q000379:methods; D005260:Female; D005532:Foot Deformities, Congenital / Q000235:genetics*; D005838:Genotype; D006228:Hand Deformities, Congenital / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009154:Mutation / Q000235:genetics*; D010375:Pedigree; D010641:Phenotype; D060888:Real-Time Polymerase Chain Reaction; D013199:Stapes / Q000002:abnormalities*; D013580:Synostosis / Q000235:genetics*; D013639:Tarsal Bones / Q000002:abnormalities*