Mosaic Deletions of Known Genes Explain Skeletal Dysplasias With High and Low Bone Mass
| Autor: | Mari Muurinen, Fulya Taylan, Symeon Tournis, Jesper Eisfeldt, Alexia Balanika, Heleni Vastardis, Sirpa Ala‐Mello, Outi Mäkitie, Alice Costantini |
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| Přispěvatelé: | CAMM - Research Program for Clinical and Molecular Metabolism, Children's Hospital, University of Helsinki, HUS Children and Adolescents, HUSLAB, Department of Medical and Clinical Genetics, Clinicum, Lastentautien yksikkö |
| Rok vydání: | 2022 |
| Předmět: |
SOMATIC MOSAICISM
Endocrinology Diabetes and Metabolism RUNX2 RUNX2 GENE AMER1 OSTEOPATHIA STRIATA MOSAICISM WHOLE-GENOME SEQUENCING REGION CLEIDOCRANIAL DYSPLASIA CHILD 3121 General medicine internal medicine and other clinical medicine CRANIAL SCLEROSIS Orthopedics and Sports Medicine SKELETAL DYSPLASIA MICRODELETION |
| Zdroj: | JBMR plus. 6(8) |
| ISSN: | 2473-4039 |
| Popis: | Mosaicism, a state in which an individual has two or more genetically distinct populations of cells in the body, can be difficult to detect because of either mild or atypical clinical presentation and limitations in the commonly used detection methods. Knowledge of the role of mosaicism is limited in many skeletal disorders, including osteopathia striata with cranial sclerosis (OSCS) and cleidocranial dysplasia (CCD). We used whole-genome sequencing (WGS) with coverage >40x to identify the genetic causes of disease in two clinically diagnosed patients. In a female patient with OSCS, we identified a mosaic 7-nucleotide frameshift deletion in exon 2 of AMER1, NM_152424.4:c.855_861del:p.(His285Glnfs*7), affecting 8.3% of the WGS reads. In a male patient with CCD, approximately 34% of the WGS reads harbored a 3710-basepair mosaic deletion, NC_000006.11:g.45514471_45518181del, starting in intron 8 of RUNX2 and terminating in the 3 ' untranslated region. Droplet digital polymerase chain reaction was used to validate these deletions and quantify the absolute level of mosaicism in each patient. Although constitutional variants in AMER1 and RUNX2 are a known cause of OSCS and CCD, respectively, the mosaic changes here reported have not been described previously. Our study indicates that mosaicism should be considered in unsolved cases of skeletal dysplasia and should be investigated with comprehensive and sensitive detection methods. (c) 2022 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research. |
| Databáze: | OpenAIRE |
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