title: Dissecting the phenotype of supernumerary marker chromosome 20 in a patient with syndromic Pierre Robin sequence: combinatorial effect of gene dosage and uniparental disomy.
abstract: Clinical phenotypes in individuals with a supernumerary marker chromosome (SMC) are mainly caused by gene dosage effects due to the genes located on the SMC. An additional effect may result from uniparental disomy (UPD). Consequently, the occurrence of UPD may be a confounding factor in identifying genotype-phenotype correlations in SMC syndromes. Here, we report on a patient that illustrates this problem; the phenotype of this patient was a consequence of a combined effect of gene dosage and UPD. The proband showed facial dysmorphisms, growth retardation and developmental delay. G-band karyotype of the proband's peripheral blood showed the presence of mosaic SMC. A SNP array analysis documented maternal UPD20 and 20p duplication. It is known that maternal UPD20 causes prenatal onset growth retardation and feeding difficulties. By contrast, duplication of 20p causes facial dysmorphisms, micrognathia, cleft palate, developmental delay and vertebral anomalies. Our classification of the proband's phenotype showed a mixture of these two effects. Therefore, we suggest the routine use of genome-wide SNP array towards the detailed genotype-phenotype correlations for SMC syndromes.
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo, Japan.
authors.forename: Kosuke
authors.initials: K
authors.lastname: Izumi
authors.affiliation: Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Noriko
authors.initials: N
authors.lastname: Kubota
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Michiko
authors.initials: M
authors.lastname: Arakawa
authors.affiliation: Department of Pediatrics, Nagano Red Cross Hospital, Nagano, Japan.
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Takayama
authors.affiliation: Department of Pediatrics, Inariyama Medical Walfare Center, Chikuma, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Harada
authors.affiliation: Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Division of Neonatology, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Tomohiko
authors.initials: T
authors.lastname: Nakamura
authors.affiliation: Division of Medical Genetics, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.|Department of Medical Genetics, Shinshu University Graduate School of Medicine, Matsumoto, Japan.
authors.forename: Eriko
authors.initials: E
authors.lastname: Nishi
authors.affiliation: Department of Laboratory Medicine, Nagano Children's Hospital, Azumino, Japan.|Life Science Research Center, Nagano Children's Hospital, Azumino, Japan.
authors.forename: Eiko
authors.initials: E
authors.lastname: Hidaka
mesh_terms: D002871:Chromosome Banding; D002890:Chromosomes, Human, Pair 20; D002972:Cleft Palate / Q000235:genetics* / Q000473:pathology; D002658:Developmental Disabilities; D005260:Female; D018628:Gene Dosage; D056726:Genetic Association Studies; D005819:Genetic Markers; D006801:Humans; D007223:Infant; D007621:Karyotyping; D008844:Micrognathism / Q000235:genetics* / Q000473:pathology; D009030:Mosaicism; D010641:Phenotype; D010855:Pierre Robin Syndrome / Q000235:genetics* / Q000473:pathology; D011247:Pregnancy; D014314:Trisomy / Q000473:pathology*
chemical_list: D005819:Genetic Markers
keywords: SNP array; growth retardation; trisomy rescue