Zhuo Ren1, Jia-Yu Yuan2, Jing Zhang3,4, Ya Tan1, Wen-Qi Chen3,4, Zhen-Tao Zhang5, Ya-Zhou Li2. 1. Department of Obstetrics and Gynecology, Peking University International Hospital Beijing 102206, China. 2. Department of Pediatric Orthopaedics, The Third Hospital of Hebei Medical University Shijiazhuang 050051, Hebei, China. 3. Prenatal Diagnosis Center, Shijiazhuang Obstetrics and Gynecology Hospital Shijiazhuang 050051, Hebei, China. 4. Key Laboratory of Maternal and Fetal Medicine of Hebei Province Shijiazhuang 050051, Hebei, China. 5. Pain Department, The People's Hospital of Langfang Langfang 065000, Hebei, China.
Abstract
BACKGROUND: HMO (Hereditary Multiple Osteochondroma), an uncommon autosomal dominant disorder, is characterized by the development of multiple osteochondromas, which are nonmalignant cartilage-capped bone tumors growing outwards from long bone metaphyses. METHODS: The present work retrospectively analyzed seven children with HMO who were enrolled for routine clinical diagnosis and treatment, including X-ray examination. Subsequent genetic detection was carried out using whole exome sequencing (WES). In addition, this work applied Sanger sequencing to be the validation approach. Moreover, this work also examined amino acid (AA) evolutionary conservatism under the influence of certain missense variants. RESULTS: The clinical indications of all seven patients and their family members were thoroughly indexed. WES identified diagnostic variants in the EXT1 or EXT2 gene in these patients. In these variants, four were reported for the first time, namely EXT1: c.1285-2A>T, EXT2: c.1139delT, EXT1: c.203G>A, and EXT1: c.1645_1673del. Familial validation revealed that three of the variants were hereditary, while the other four were de novo, which was consistent with the phenotype in each case. CONCLUSION: Our results expanded HMO variation spectrum, and laid certain foundations for the precise counseling of those affected families. AJTR
BACKGROUND: HMO (Hereditary Multiple Osteochondroma), an uncommon autosomal dominant disorder, is characterized by the development of multiple osteochondromas, which are nonmalignant cartilage-capped bone tumors growing outwards from long bone metaphyses. METHODS: The present work retrospectively analyzed seven children with HMO who were enrolled for routine clinical diagnosis and treatment, including X-ray examination. Subsequent genetic detection was carried out using whole exome sequencing (WES). In addition, this work applied Sanger sequencing to be the validation approach. Moreover, this work also examined amino acid (AA) evolutionary conservatism under the influence of certain missense variants. RESULTS: The clinical indications of all seven patients and their family members were thoroughly indexed. WES identified diagnostic variants in the EXT1 or EXT2 gene in these patients. In these variants, four were reported for the first time, namely EXT1: c.1285-2A>T, EXT2: c.1139delT, EXT1: c.203G>A, and EXT1: c.1645_1673del. Familial validation revealed that three of the variants were hereditary, while the other four were de novo, which was consistent with the phenotype in each case. CONCLUSION: Our results expanded HMO variation spectrum, and laid certain foundations for the precise counseling of those affected families. AJTR
Authors: Marina Mordenti; Enrico Ferrari; Elena Pedrini; Nicola Fabbri; Laura Campanacci; Marco Muselli; Luca Sangiorgi Journal: Am J Med Genet A Date: 2013-02-08 Impact factor: 2.802
Authors: Sue Richards; Nazneen Aziz; Sherri Bale; David Bick; Soma Das; Julie Gastier-Foster; Wayne W Grody; Madhuri Hegde; Elaine Lyon; Elaine Spector; Karl Voelkerding; Heidi L Rehm Journal: Genet Med Date: 2015-03-05 Impact factor: 8.822