title: Molecular characterization of a rare analphoid supernumerary marker chromosome derived from 7q35 → qter: a case report.
abstract: BACKGROUND
  Analphoid supernumerary marker chromosomes (aSMC) constitute one of the smallest groups of SMC, and are characterized by a centromeric constriction but no detectable alpha-satellite DNA. These marker chromosomes cannot be properly identified by conventional banding techniques alone, and molecular cytogenetic methods are necessary for a detailed characterization. Analphoid SMC derived from chromosome 7 are extremely rare, with only five cases reported so far.
  
  
  METHODS
  In this work we report an aSMC involving the terminal long arm of chromosome 7 in a 10-year-old boy with multiple dysmorphic features and severe development delay. Cytogenetic analysis revealed a mosaic karyotype with the presence of an extra SMC,de novo, in 20% of lymphocytes and 73% of fibroblast cells. Next, we performed FISH analysis with multiple DNA probes and cCGH analysis. This identified the origin of the SMC as an analphoid marker resulting of invdup rearrangement of 7q35-qter region. Affimetrix CytoScan HD array analysis redefined the aSMC as a 15.42 Mb gain at 7q35-q36.3 (minimum tetraplicated region-chr7: 143,594,973-159,119,707; GRCh37/hg19) of maternal origin that encloses 67 OMIM genes, 16 of which associated to disease. Uniparental disomy of chromosome 7 (UPD 7) has been excluded.
  
  
  CONCLUSIONS
  We report the first patient with an aSMC(7) derived from the terminal 7q region who has been molecularly and clinically full characterized. The use of SNParray in the characterization of SMC reveals to be a powerful tool, giving information not only about copy number variation but also about loss-of-heterozygosity and parental origin. We conclude that an integrated genome-wide copy number variation analysis, if possible associated to FISH and gene expression studies, could facilitate in the future the difficult task of establishing accurate genotype-phenotype correlations and help to improve genetic counselling.
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Bárbara
authors.initials: B
authors.lastname: Marques
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Ferreira
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Filomena
authors.initials: F
authors.lastname: Brito
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Sónia
authors.initials: S
authors.lastname: Pedro
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Cristina
authors.initials: C
authors.lastname: Alves
authors.affiliation: Serviço de Genética Médica, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal.
authors.forename: Teresa
authors.initials: T
authors.lastname: Lourenço
authors.affiliation: Serviço de Genética Médica, Hospital de Dona Estefânia, Centro Hospitalar de Lisboa Central, Rua Jacinta Marto, 1169-045 Lisboa, Portugal.
authors.forename: Marta
authors.initials: M
authors.lastname: Amorim
authors.affiliation: Unidade de Citogenética, Departamento de Genética Humana, Instituto Nacional de Saúde Doutor Ricardo Jorge, I.P, Avenida Padre Cruz, 1649-016 Lisboa, Portugal.
authors.forename: Hildeberto
authors.initials: H
authors.lastname: Correia
keywords: 7q duplication; Analphoid supernumerary marker chromosome; Chromosome 7; Neocentromere; Partial 7q tetrasomy