title: Clinical and molecular cytogenetic analyses of four families with 1q21.1 microdeletion or microduplication.
abstract: BACKGROUND
  Little information is available regarding the penetrance of 1q21.1 copy number variants (CNVs). In the present study, we explored the clinical significance of 1q21.1 microdeletion or microduplication.
  
  
  METHODS
  In four families, chromosome karyotype was analyzed using G-banding karyotype analysis technology. CNVs were detected using array-comparative genomic hybridization (aCGH) and then a quantitative polymerase chain reaction (qPCR) was used to validate candidate CNVs. Sequence signature in the breakpoint region was analyzed using University of California Santa Cruz (UCSC) databases.
  
  
  RESULTS
  Except for karyotype 45, XX, der (13, 14) (q10, q10) in the mother (I2) of family 2, the karyotype was normal in all other members of the four families. In the mother (I2) and fetus (II2) of family 1, in newborn (II1) of family 2 and in fetus (II1) of family 3, there was 1.22-Mb heterozygous microdeletion in the chromosome 1q21.1q21.2 region. The child (II1) of family 4 had a 1.46-Mb heterozygous microduplication in the chromosome 1q21.1q21.2 region. The results of the qPCR were consistent with that of aCGH. There was large number of low copy repeats (LCRs) in the breakpoint region found by analysis of the UCSC database, and multiple LCRs were matched with sequences in the chromosome 1 short-arm region.
  
  
  CONCLUSIONS
  1q21.1 microdeletion and microduplication exhibit a variety of clinical manifestations and the specificity of their clinical features is not high. The penetrance of the distal 1q21.1 microdeletion may be affected by other factors in the present study. In summary, we report the discovery of a new distal 1q21.1 microduplication, which enriches the CNV spectrum in the 1q21.1 region and is conducive to prenatal genetic counseling.
authors.affiliation: Institute of Medical Genetics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Hong-Dan
authors.initials: HD
authors.lastname: Wang
authors.affiliation: Department of Cardiovascular Ultrasound, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Liu
authors.affiliation: Institute of Medical Genetics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Dong
authors.initials: D
authors.lastname: Wu
authors.affiliation: Institute of Medical Genetics, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Li
authors.affiliation: Department of Cardiovascular Ultrasound, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Cun-Ying
authors.initials: CY
authors.lastname: Cui
authors.affiliation: Department of Cardiovascular Ultrasound, Henan Provincial People's Hospital, Zhengzhou University People's Hospital, Zhengzhou, China.
authors.forename: Lian-Zhong
authors.initials: LZ
authors.lastname: Zhang
authors.affiliation: Department of Ultrasound, the Affiliated Cancer Hospital, Zhengzhou University, Zhengzhou, China.
authors.forename: Cheng-Zeng
authors.initials: CZ
authors.lastname: Wang
mesh_terms: D000015:Abnormalities, Multiple / Q000175:diagnosis* / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D002871:Chromosome Banding; D002872:Chromosome Deletion; D058674:Chromosome Duplication; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D020732:Cytogenetic Analysis; D056915:DNA Copy Number Variations; D005260:Female; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D007223:Infant; D008297:Male; D058627:Megalencephaly / Q000175:diagnosis* / Q000235:genetics*; D010375:Pedigree; D019683:Penetrance; D010641:Phenotype; D016216:Ultrasonography, Prenatal; D055815:Young Adult
keywords: 1q21.1 microdeletion; 1q21.1 microduplication; array-comparative genomic hybridization; copy number variations