The First Nationwide Survey and Genetic Analyses of Bardet-Biedl Syndrome in Japan.
Bardet-Biedl syndrome (BBS) is an autosomal recessive disorder characterized by central obesity, mental impairment, rod-cone dystrophy, polydactyly, hypogonadism in males, and renal abnormalities. The causative genes have been identified as BBS1-19. In Western countries, this disease is often reported, but remains undiagnosed in many patients until later in life, while only a few patients with no mutations identified have been reported in Japan. We thus conducted the first nationwide survey of BBS in Japan by sending questionnaires to 2,166 clinical departments with board-certified specialists and found 7 patients with clinically definite BBS. We performed exome analyses combined with analyses of mRNA and protein in these patients. We identified 2 novel mutations in the BBS5 gene (p.R89X and IVS7-27 T>G) in 2 sibling patients. The latter mutation that resided far from the authentic splicing site was associated with skipping of exon 8. We also found 3 previously reported mutations in the BBS2 (p.R413X and p.R480X) and BBS7 (p.C243Y) genes in 2 patients. To our knowledge, a nationwide survey of BBS has not been reported in any other country. In addition, this is the first study to identify genetic alterations in Japanese patients with BBS. Our results indicate that BBS in Japan is genetically heterogeneous and at least partly shares genetic features with BBS in other countries.
Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Sakai, Japan; Department of Neurology, Kinki University Faculty of Medicine, Osakasayama, Japan.
Makito
M
Hirano
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Wataru
W
Satake
Department of Pediatrics, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Kenji
K
Ihara
Department of Pediatrics, Fujita Health University, Toyoake, Japan.
Ikuya
I
Tsuge
Department of Pediatrics, Tokushima University, Tokushima, Japan.
Shuji
S
Kondo
Department of Nephrology, National Center for Child Health and Development, Tokyo, Japan.
Ken
K
Saida
Department of Pediatrics, Haga Red Cross Hospital, Mooka, Japan.
Hiroyuki
H
Betsui
Department of Pediatrics, Kyushu University Graduate School of Medicine, Fukuoka, Japan.
Kazuhiro
K
Okubo
Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Sakai, Japan.
Hikaru
H
Sakamoto
Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Sakai, Japan; Department of Neurology, Kinki University Faculty of Medicine, Osakasayama, Japan.
Shuichi
S
Ueno
Department of Ophthalmology, Osaka University Graduate School of Medicine, Suita, Japan.
Yasushi
Y
Ikuno
Department of Gastrointestinal Oncology, Osaka Medical Center for Cancer and Cardiovascular Diseases, Osaka, Japan.
Ryu
R
Ishihara
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Hiromi
H
Iwahashi
Department of Geriatric Medicine, Osaka University Graduate School of Medicine, Suita, Japan.
Mitsuru
M
Ohishi
Department of Pediatric Neurology, Osaka Medical Center and Research Institute for Maternal and Child Health, Izumi, Japan.
Toshiyuki
T
Mano
Department of Molecular Neuroscience, Osaka University Graduate School of Medicine, Suita, Japan.
Toshihide
T
Yamashita
Department of Computational Biology, Graduate School of Frontier Sciences, The University of Tokyo, Kashiwa, Japan.
Yutaka
Y
Suzuki
Department of Neurology, Sakai Hospital Kinki University Faculty of Medicine, Sakai, Japan.
Yusaku
Y
Nakamura
Department of Neurology, Kinki University Faculty of Medicine, Osakasayama, Japan.
Susumu
S
Kusunoki
Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, Kobe, Japan.
Tatsushi
T
Toda
D000293:Adolescent; D020788:Bardet-Biedl Syndrome / Q000453:epidemiology* / Q000235:genetics; D002648:Child; D002675:Child, Preschool; D003598:Cytoskeletal Proteins; D059472:Exome / Q000235:genetics; D005260:Female; D006801:Humans; D007564:Japan / Q000453:epidemiology; D008297:Male; D009154:Mutation / Q000235:genetics; D020411:Oligonucleotide Array Sequence Analysis; D028044:Phosphate-Binding Proteins; D011506:Proteins / Q000235:genetics; D011795:Surveys and Questionnaires; D055815:Young Adult
C487434:BBS5 protein, human; D003598:Cytoskeletal Proteins; D028044:Phosphate-Binding Proteins; D011506:Proteins