Kentaro Kurata1, Katsuhiro Hosono1, Akiko Hikoya1, Akihiko Kato2, Hirotomo Saitsu3, Shinsei Minoshima4, Tsutomu Ogata5, Yoshihiro Hotta6. 1. Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka, 431-3192, Japan. 2. Blood Purification Unit, Hamamatsu University Hospital, Shizuoka, Japan. 3. Department of Biochemistry, Hamamatsu University School of Medicine, Shizuoka, Japan. 4. Department of Photomedical Genomics, Preeminent Medical Photonics Education and Research Center, Institute for Medical Photonics Research, Hamamatsu University School of Medicine, Shizuoka, Japan. 5. Department of Pediatrics, Hamamatsu University School of Medicine, Shizuoka, Japan. 6. Department of Ophthalmology, Hamamatsu University School of Medicine, 1-20-1 Handayama, Hamamatsu-shi, Higashi-ku, Shizuoka, 431-3192, Japan. hotta@hama-med.ac.jp.
Abstract
PURPOSE: Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by retinal dystrophy, renal dysfunction, central obesity, mental impairment, polydactyly, and hypogonadism. Only limited information on BBS is available from Japanese patients. In addition, there are currently no reports of Japanese patients with BBS caused by BBS10 mutations. The purpose of this study was to present the characteristics of a Japanese patient with BBS caused by BBS10 mutations. PATIENT AND METHODS: The patient was a 22-year-old Japanese woman. Comprehensive ophthalmic examinations, including visual acuity measurements, perimetry, electroretinography (ERG), fundus autofluorescence imaging, and optical coherence tomography, were performed. Trio-based whole-exome sequencing was performed to identify potential pathogenic mutations, confirmed by Sanger sequencing. RESULTS: The patient showed neither renal malformation nor dysfunction, and visual impairment seemed to be relatively mild for BBS. The fundus examination revealed diffuse retinal degeneration without pigmentary deposits, and ERG scans showed undetectable responses. She had a history of surgically corrected polydactyly, and displayed symptoms of obesity. There was also a menstrual irregularity that could require progestin administration. Genetic analysis revealed compound heterozygous BBS10 mutations in the patient: a novel missense mutation c.98G>A [p.(G33E)], and a novel nonsense mutation c.2125A>T [p.(R709*)]. CONCLUSION: To our knowledge, this is the first description of a Japanese patient with BBS caused by BBS10 mutations. The clinical characteristics of our patient were mild, as neither renal impairment nor legal blindness was observed. Early diagnosis would play a role in providing counseling, and in some cases, therapeutic interventions for BBS patients.
PURPOSE:Bardet-Biedl syndrome (BBS) is a rare autosomal recessive disorder characterized by retinal dystrophy, renal dysfunction, central obesity, mental impairment, polydactyly, and hypogonadism. Only limited information on BBS is available from Japanese patients. In addition, there are currently no reports of Japanese patients with BBS caused by BBS10 mutations. The purpose of this study was to present the characteristics of a Japanese patient with BBS caused by BBS10 mutations. PATIENT AND METHODS: The patient was a 22-year-old Japanese woman. Comprehensive ophthalmic examinations, including visual acuity measurements, perimetry, electroretinography (ERG), fundus autofluorescence imaging, and optical coherence tomography, were performed. Trio-based whole-exome sequencing was performed to identify potential pathogenic mutations, confirmed by Sanger sequencing. RESULTS: The patient showed neither renal malformation nor dysfunction, and visual impairment seemed to be relatively mild for BBS. The fundus examination revealed diffuse retinal degeneration without pigmentary deposits, and ERG scans showed undetectable responses. She had a history of surgically corrected polydactyly, and displayed symptoms of obesity. There was also a menstrual irregularity that could require progestin administration. Genetic analysis revealed compound heterozygous BBS10 mutations in the patient: a novel missense mutation c.98G>A [p.(G33E)], and a novel nonsense mutation c.2125A>T [p.(R709*)]. CONCLUSION: To our knowledge, this is the first description of a Japanese patient with BBS caused by BBS10 mutations. The clinical characteristics of our patient were mild, as neither renal impairment nor legal blindness was observed. Early diagnosis would play a role in providing counseling, and in some cases, therapeutic interventions for BBSpatients.
Authors: Jean Muller; C Stoetzel; M C Vincent; C C Leitch; V Laurier; J M Danse; S Hellé; V Marion; V Bennouna-Greene; S Vicaire; A Megarbane; J Kaplan; V Drouin-Garraud; M Hamdani; S Sigaudy; C Francannet; J Roume; P Bitoun; A Goldenberg; N Philip; S Odent; J Green; M Cossée; E E Davis; N Katsanis; D Bonneau; A Verloes; O Poch; J L Mandel; H Dollfus Journal: Hum Genet Date: 2010-02-23 Impact factor: 4.132
Authors: Tina Duelund Hjortshøj; Karen Grønskov; Alisdair R Philp; Darryl Y Nishimura; Ruth Riise; Val C Sheffield; Thomas Rosenberg; Karen Brøndum-Nielsen Journal: Hum Mutat Date: 2010-04 Impact factor: 4.878