title: Extensive gene deletions in Japanese patients with Diamond-Blackfan anemia.
abstract: Fifty percent of Diamond-Blackfan anemia (DBA) patients possess mutations in genes coding for ribosomal proteins (RPs). To identify new mutations, we investigated large deletions in the RP genes RPL5, RPL11, RPL35A, RPS7, RPS10, RPS17, RPS19, RPS24, and RPS26. We developed an easy method based on quantitative-PCR in which the threshold cycle correlates to gene copy number. Using this approach, we were able to diagnose 7 of 27 Japanese patients (25.9%) possessing mutations that were not detected by sequencing. Among these large deletions, similar results were obtained with 6 of 7 patients screened with a single nucleotide polymorphism array. We found an extensive intragenic deletion in RPS19, including exons 1-3. We also found 1 proband with an RPL5 deletion, 1 patient with an RPL35A deletion, 3 with RPS17 deletions, and 1 with an RPS19 deletion. In particular, the large deletions in the RPL5 and RPS17 alleles are novel. All patients with a large deletion had a growth retardation phenotype. Our data suggest that large deletions in RP genes comprise a sizable fraction of DBA patients in Japan. In addition, our novel approach may become a useful tool for screening gene copy numbers of known DBA genes.
authors.affiliation: Department of Safety Research on Blood and Biological Products, National Institute of Infectious Diseases, Tokyo, Japan.
authors.forename: Madoka
authors.initials: M
authors.lastname: Kuramitsu
authors.forename: Aiko
authors.initials: A
authors.lastname: Sato-Otsubo
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Morio
authors.forename: Masatoshi
authors.initials: M
authors.lastname: Takagi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Toki
authors.forename: Kiminori
authors.initials: K
authors.lastname: Terui
authors.forename: RuNan
authors.initials: R
authors.lastname: Wang
authors.forename: Hitoshi
authors.initials: H
authors.lastname: Kanno
authors.forename: Shouichi
authors.initials: S
authors.lastname: Ohga
authors.forename: Akira
authors.initials: A
authors.lastname: Ohara
authors.forename: Seiji
authors.initials: S
authors.lastname: Kojima
authors.forename: Toshiyuki
authors.initials: T
authors.lastname: Kitoh
authors.forename: Kumiko
authors.initials: K
authors.lastname: Goi
authors.forename: Kazuko
authors.initials: K
authors.lastname: Kudo
authors.forename: Tadashi
authors.initials: T
authors.lastname: Matsubayashi
authors.forename: Nobuo
authors.initials: N
authors.lastname: Mizue
authors.forename: Michio
authors.initials: M
authors.lastname: Ozeki
authors.forename: Atsuko
authors.initials: A
authors.lastname: Masumi
authors.forename: Haruka
authors.initials: H
authors.lastname: Momose
authors.forename: Kazuya
authors.initials: K
authors.lastname: Takizawa
authors.forename: Takuo
authors.initials: T
authors.lastname: Mizukami
authors.forename: Kazunari
authors.initials: K
authors.lastname: Yamaguchi
authors.forename: Seishi
authors.initials: S
authors.lastname: Ogawa
authors.forename: Etsuro
authors.initials: E
authors.lastname: Ito
authors.forename: Isao
authors.initials: I
authors.lastname: Hamaguchi
mesh_terms: D029503:Anemia, Diamond-Blackfan / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044466:Asian People / Q000235:genetics; D002675:Child, Preschool; D004252:DNA Mutational Analysis / Q000379:methods; D005260:Female; D017353:Gene Deletion; D056726:Genetic Association Studies; D006801:Humans; D007223:Infant; D007231:Infant, Newborn; D007564:Japan; D008297:Male; D046228:Microarray Analysis / Q000379:methods; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results; D012269:Ribosomal Proteins / Q000235:genetics*
chemical_list: C489281:RPL35A protein, human; D012269:Ribosomal Proteins; C549166:ribosomal protein L5, human; C037084:ribosomal protein S17; C040343:ribosomal protein S19