title: Novel SBDS mutations caused by gene conversion in Japanese patients with Shwachman-Diamond syndrome.
abstract: Shwachman-Diamond syndrome (SDS; OMIM 260400) is an autosomal recessive disorder characterized by exocrine pancreatic insufficiency, bone marrow dysfunction and metaphyseal chondrodysplasia. SDS is caused by mutations in SBDS, an uncharacterized gene. A previous study in SDS patients largely of European ancestry found that most SBDS mutations occurred within a approximately 240-bp region of exon 2 and resulted from gene conversion due to recombination with a pseudogene, SBDSP. It is unknown, however, whether these findings are applicable to other ethnic groups. To address this question, we examined SBDS mutations in six Japanese families with SDS by direct sequencing. We identified compound heterozygous mutations in four families: two were recurrent (96-97insA, 258+2T>C), and three were novel [292-295delAAAG, (183-184TA>CT +201A>G), (141C>T+183-184TA>CT+201A>G)] mutations. Most of these mutations also appear to result from gene conversion, but the conversion events occurred at various sites between intron 1 and exon 3. Thus, gene conversion mutations in SBDS are common to different ethnic groups, but they are not confined to a limited region of the gene.
authors.affiliation: Laboratory for Bone and Joint Diseases, SNP Research Center, RIKEN, c/o Institute of Medical Science, University of Tokyo, 4-6-1 Shirokanedai, 108-8639 Minato-ku, Tokyo, Japan.
authors.forename: Eiji
authors.initials: E
authors.lastname: Nakashima
authors.forename: Akihiko
authors.initials: A
authors.lastname: Mabuchi
authors.forename: Yoshio
authors.initials: Y
authors.lastname: Makita
authors.forename: Mitsuo
authors.initials: M
authors.lastname: Masuno
authors.forename: Hirofumi
authors.initials: H
authors.lastname: Ohashi
authors.forename: Gen
authors.initials: G
authors.lastname: Nishimura
authors.forename: Shiro
authors.initials: S
authors.lastname: Ikegawa
mesh_terms: D000483:Alleles; D001483:Base Sequence; D001855:Bone Marrow Diseases / Q000235:genetics*; D016022:Case-Control Studies; D004252:DNA Mutational Analysis; D005006:Ethnicity / Q000235:genetics; D010188:Exocrine Pancreatic Insufficiency / Q000235:genetics*; D005785:Gene Conversion; D005808:Genes, Recessive; D006801:Humans; D007564:Japan; D009154:Mutation; D010009:Osteochondrodysplasias / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D013577:Syndrome
chemical_list: D011506:Proteins; C470521:SBDS protein, human