Kazuhiro Iwama1,2, Takeshi Mizuguchi1, Jun-Ichi Takanashi3, Hidehiro Shibayama4, Minobu Shichiji5, Susumu Ito5, Hirokazu Oguni5, Toshiyuki Yamamoto6, Akiko Sekine7, Shun Nagamine7, Yoshio Ikeda7, Hiroya Nishida8, Satoko Kumada8, Takeshi Yoshida9, Tomonari Awaya9,10, Ryuta Tanaka11, Ryo Chikuchi12, Hisayoshi Niwa12, Yu-Ichi Oka13, Satoko Miyatake1, Mitsuko Nakashima1, Atsushi Takata1, Noriko Miyake1, Shuichi Ito2, Hirotomo Saitsu14, Naomichi Matsumoto1. 1. Department of Human Genetics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 2. Department of Pediatrics, Graduate School of Medicine, Yokohama City University, Yokohama, Japan. 3. Department of Pediatrics and Pediatric Neurology, Tokyo Women's Medical University, Yachiyo Medical Center, Yachiyo, Japan. 4. Department of Neurology, Kameda Medical Center, Kamogawa, Japan. 5. Department of Pediatrics, Tokyo Women's Medical University, Tokyo, Japan. 6. Institute of Medical Genetics, Tokyo Women's Medical University, Tokyo, Japan. 7. Department of Neurology, Gunma University Graduate School of Medicine, Maebashi, Japan. 8. Department of Neuropediatrics, Tokyo Metropolitan Neurological Hospital, Tokyo, Japan. 9. Department of Pediatrics, Kyoto University Graduate School of Medicine, Kyoto, Japan. 10. Department of Anatomy and Developmental Biology, Kyoto University Graduate School of Medicine, Kyoto, Japan. 11. Department of Child Health, Faculty of Medicine, University of Tsukuba, Tsukuba, Japan. 12. Department of Neurology, Kariya Toyota General Hospital, Kariya, Japan. 13. Department of Neurosurgery, Nagoya City University Hospital, Nagoya, Japan. 14. Department of Biochemistry, Hamamatsu University School of Medicine, Hamamatsu, Japan.
Abstract
BACKGROUND: Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. MATERIALS AND METHODS: Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. RESULTS: Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). CONCLUSION: Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.
BACKGROUND:Leukoencephalopathy with brain calcifications and cysts (LCC) is neuroradiologically characterized by leukoencephalopathy, intracranial calcification, and cysts. Coats plus syndrome is also characterized by the same neuroradiological findings together with defects in retinal vascular development. Indeed, LCC and Coats plus were originally considered to be the same clinical entity termed cerebroretinal microangiopathy with calcifications and cysts, but evidence suggests that they are genetically distinct. Mutations in CTS telomere maintenance complex component 1 (CTC1) and small nucleolar RNA, C/D box 118 (SNORD118) genes have been found to cause Coats plus and LCC, respectively. MATERIALS AND METHODS: Eight unrelated families with LCC were recruited. These patients typically showed major neuroradiological findings of LCC with no signs of extra-neurological manifestations such as retinal abnormality, gastrointestinal bleeding, or hematological abnormalities. SNORD118 was examined by Sanger sequencing in these families. RESULTS: Seven out of eight probands carry compound heterozygous mutations, suggesting that SNORD118 mutations are the major cause of LCC. We identified a total of eight mutation, including four that were novel. Some of the variants identified in this study present heterozygously in public databases with an extremely rare frequency (<0.1%). CONCLUSION: Biallelic SNORD118 mutations were exclusively found in most unrelated families with LCC.
Authors: Minjie Zhang; Irena T Hwang; Kongpan Li; Jianhui Bai; Jian-Fu Chen; Tsachy Weissman; James Y Zou; Zhipeng Lu Journal: Genome Res Date: 2022-03-24 Impact factor: 9.438
Authors: Minjie Zhang; Kongpan Li; Jianhui Bai; Willem A Velema; Chengqing Yu; Ryan van Damme; Wilson H Lee; Maia L Corpuz; Jian-Fu Chen; Zhipeng Lu Journal: Nat Commun Date: 2021-04-20 Impact factor: 17.694