title: Mapping Breakpoints of Complex Chromosome Rearrangements Involving a Partial Trisomy 15q23.1-q26.2 Revealed by Next Generation Sequencing and Conventional Techniques.
abstract: Complex chromosome rearrangements (CCRs), which are rather rare in the whole population, may be associated with aberrant phenotypes. Next-generation sequencing (NGS) and conventional techniques, could be used to reveal specific CCRs for better genetic counseling. We report the CCRs of a girl and her mother, which were identified using a combination of NGS and conventional techniques including G-banding, fluorescence in situ hybridization (FISH) and PCR. The girl demonstrated CCRs involving chromosomes 3 and 8, while the CCRs of her mother involved chromosomes 3, 5, 8, 11 and 15. HumanCytoSNP-12 Chip analysis identified a 35.4 Mb duplication on chromosome 15q21.3-q26.2 in the proband and a 1.6 Mb microdeletion at chromosome 15q21.3 in her mother. The proband inherited the rearranged chromosomes 3 and 8 from her mother, and the duplicated region on chromosome 15 of the proband was inherited from the mother. Approximately one hundred genes were identified in the 15q21.3-q26.2 duplicated region of the proband. In particular, TPM1, SMAD6, SMAD3, and HCN4 may be associated with her heart defects, and HEXA, KIF7, and IDH2 are responsible for her developmental and mental retardation. In addition, we suggest that a microdeletion on the 15q21.3 region of the mother, which involved TCF2, TCF12, ADMA10 and AQP9, might be associated with mental retardation. We delineate the precise structures of the derivative chromosomes, chromosome duplication origin and possible molecular mechanisms for aberrant phenotypes by combining NGS data with conventional techniques.
authors.affiliation: Laboratory of Clinical Genetics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Yangzhou University, Huai'an, China.
authors.forename: Qiong
authors.initials: Q
authors.lastname: Pan
authors.affiliation: Department of Medical Genetics, Hunan Provincial Maternal and Child Health Hospital, Changsha, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Huai'an, China.
authors.forename: Liangrong
authors.initials: L
authors.lastname: Han
authors.affiliation: Laboratory of Clinical Genetics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Yangzhou University, Huai'an, China.
authors.forename: Xin
authors.initials: X
authors.lastname: Jing
authors.affiliation: CapitalBio Genomics Co., Ltd, Dongguan, China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Liu
authors.affiliation: BGI-Shenzhen, Shenzhen, China.
authors.forename: Chuanchun
authors.initials: C
authors.lastname: Yang
authors.affiliation: Laboratory of Clinical Genetics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Yangzhou University, Huai'an, China.
authors.forename: Fengting
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Laboratory of Clinical Genetics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Yangzhou University, Huai'an, China.
authors.forename: Yue
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Department of Pediatrics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Huai'an, China.
authors.forename: Hongni
authors.initials: H
authors.lastname: Yue
authors.affiliation: Laboratory of Clinical Genetics, Huai'an Maternity and Child Health Care Hospital of Jiangsu Province, Yangzhou University, Huai'an, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Ning
mesh_terms: D000328:Adult; D002869:Chromosome Aberrations; D002871:Chromosome Banding; D002884:Chromosomes, Human, Pair 15 / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D059014:High-Throughput Nucleotide Sequencing / Q000379:methods*; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D017422:Sequence Analysis, DNA / Q000379:methods*; D014314:Trisomy