2026-04-17T05:49:47Zhttps://recercat.cat/oai/request

oai:recercat.cat:2445/1935642025-12-04T22:45:54Zcom_2072_1057col_2072_478825col_2072_478917

00925njm 22002777a 4500 dc Ovejero, Diana author Garcia-Giralt, Natalia author Rabionet Janssen, Raquel author Balcells Comas, Susana author Grinberg Vaisman, Daniel Raúl author Pérez-Jurado, Luis Alberto author Nogués, Xavier author Etxebarria Foronda, Iñigo author 2023-02-14T09:17:31Z 2023-05-26T05:10:25Z 2022 2023-02-14T09:17:31Z High bone mass (HBM) disorders are a clinically and genetically heterogeneous subgroup of rare skeletal dysplasias. Here we present a case of a previously unreported familial skeletal dysplasia characterized by HBM and lucent bone lesions that we aimed to clinically characterize and genetically investigate. For phenotyping, we reviewed past clinical records and imaging tests, and performed physical examination (PE), bone densitometry, and mineral panels in affected individuals, including a male proband, his son and daughter, in addition to unaffected controls, including the proband's wife and brother. Affected individuals also underwent impact microindentation (IMI). In an effort to elucidate the disorder's molecular etiology, whole exome sequencing (WES) was performed in all individuals to filter for rare variants present only in affected ones. The cases displayed a unique skeletal phenotype with a mix of sclerotic features and lucent bone lesions, and high IMI values. Bone mineral density was very elevated in the proband and his daughter. The proband's daughter also exhibited idiopathic scoliosis (IS), in addition to mild thrombocytopenia and mild structural thyroid abnormalities, which were the only extra-skeletal abnormalities identified. WES analysis yielded 5 rare putative pathogenic variants in affected members in genes that are associated with bone metabolism including: SEM4AD, TBX18, PTCH1, PTK7, and ADGRE5. The PTK7 variant appeared as possibly implicated in the development of IS while the TBX18 and SEMA4D variants stood out as the strongest candidates for the lucent bone lesions and HBM, respectively, given their high predicted pathogenicity and putative role in bone biology. Variant functionality should be addressed in the future to assess their implication in skeletal metabolism as it is the first time that mutations in TBX18 and SEMA4D have been associated to bone developmental lesions and mineral metabolism in a clinical setting. Genètica Malalties dels ossos Displàsia fibrosa òssia Densitometria òssia Genetics Bone diseases Fibrous dysplasia of bone Bone densitometry Clinical description and genetic analysis of a novel familial skeletal dysplasia characterized by high bone mass and lucent bone lesions