A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations
Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2. Recent investigations have discovered several other autosomal recessive genes responsible for OI. Among t...
| Main Authors: | , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2018-12-01
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| Series: | Bone Reports |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352187218300494 |
| _version_ | 1818545784841306112 |
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| author | Adolfredo Santana Jeanne M. Franzone Cristina M. McGreal Richard W. Kruse Michael B. Bober |
| author_facet | Adolfredo Santana Jeanne M. Franzone Cristina M. McGreal Richard W. Kruse Michael B. Bober |
| author_sort | Adolfredo Santana |
| collection | DOAJ |
| description | Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2. Recent investigations have discovered several other autosomal recessive genes responsible for OI. Among these genes is LEPRE1, which is involved in post-translational modifications of collagen. To date, more than 40 LEPRE1 mutations have been described. One of these mutations is carried by 1.5% of West Africans and 0.4% of African Americans, and is associated with OI Type VIII. We describe the case of a five year old male with a moderate form of OI and compound heterozygous LEPRE1 mutations (c.1080 + 1G > T; c.1646 T > G, p.Met549Arg). He was diagnosed shortly after birth following a skeletal survey demonstrating multiple healing fractures as well as lower extremity deformity suggestive of remote fractures. He was then without a fracture until a calvarial fracture at 18 months of age, a femur fracture at 4 years and seven months and a second femur fracture at 5 years and 4 months. He walked at age 14 months and has been an active boy. Pamidronate infusions began at seven weeks of age and were discontinued at three years of age due to increased bone mineral density and absence of fractures. Type VIII OI typically causes a severe to lethal phenotype presenting at birth with severe osteopenia, congenital fractures and other clinical manifestations. Only a few individuals have survived to childhood. This case description serves to expand the clinical phenotyping of this recessive form of OI into the more moderate spectrum. Keywords: Osteogenesis imperfecta, Non-collagen I osteogenesis imperfecta, LEPRE1, Recessive osteogenesis imperfecta |
| first_indexed | 2024-12-12T07:44:34Z |
| format | Article |
| id | doaj.art-80453408d3c048fc848481b08d75c6aa |
| institution | Directory Open Access Journal |
| issn | 2352-1872 |
| language | English |
| last_indexed | 2024-12-12T07:44:34Z |
| publishDate | 2018-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Bone Reports |
| spelling | doaj.art-80453408d3c048fc848481b08d75c6aa2022-12-22T00:32:39ZengElsevierBone Reports2352-18722018-12-019132135A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutationsAdolfredo Santana0Jeanne M. Franzone1Cristina M. McGreal2Richard W. Kruse3Michael B. Bober4Department of Orthopaedic Surgery, Alfred I. duPont Hospital for Children, Wilmington, DE, United StatesDepartment of Orthopaedic Surgery, Alfred I. duPont Hospital for Children, Wilmington, DE, United StatesDivision of Genetics, Department of Pediatrics, Alfred I. duPont Hospital for, Children, Wilmington, DE, United StatesDepartment of Orthopaedic Surgery, Alfred I. duPont Hospital for Children, Wilmington, DE, United StatesDivision of Genetics, Department of Pediatrics, Alfred I. duPont Hospital for, Children, Wilmington, DE, United States; Corresponding author at: Alfred I. duPont Hospital for Children, 1600 Rockland Road, Wilmington, DE 19803, United States.Osteogenesis imperfecta (OI) is a genetic disorder causing skeletal fragility, multiple fractures, and other extraskeletal manifestations. Most cases are caused by mutations in COL1A1 or COL1A2. Recent investigations have discovered several other autosomal recessive genes responsible for OI. Among these genes is LEPRE1, which is involved in post-translational modifications of collagen. To date, more than 40 LEPRE1 mutations have been described. One of these mutations is carried by 1.5% of West Africans and 0.4% of African Americans, and is associated with OI Type VIII. We describe the case of a five year old male with a moderate form of OI and compound heterozygous LEPRE1 mutations (c.1080 + 1G > T; c.1646 T > G, p.Met549Arg). He was diagnosed shortly after birth following a skeletal survey demonstrating multiple healing fractures as well as lower extremity deformity suggestive of remote fractures. He was then without a fracture until a calvarial fracture at 18 months of age, a femur fracture at 4 years and seven months and a second femur fracture at 5 years and 4 months. He walked at age 14 months and has been an active boy. Pamidronate infusions began at seven weeks of age and were discontinued at three years of age due to increased bone mineral density and absence of fractures. Type VIII OI typically causes a severe to lethal phenotype presenting at birth with severe osteopenia, congenital fractures and other clinical manifestations. Only a few individuals have survived to childhood. This case description serves to expand the clinical phenotyping of this recessive form of OI into the more moderate spectrum. Keywords: Osteogenesis imperfecta, Non-collagen I osteogenesis imperfecta, LEPRE1, Recessive osteogenesis imperfectahttp://www.sciencedirect.com/science/article/pii/S2352187218300494 |
| spellingShingle | Adolfredo Santana Jeanne M. Franzone Cristina M. McGreal Richard W. Kruse Michael B. Bober A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations Bone Reports |
| title | A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations |
| title_full | A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations |
| title_fullStr | A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations |
| title_full_unstemmed | A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations |
| title_short | A moderate form of osteogenesis imperfecta caused by compound heterozygous LEPRE1 mutations |
| title_sort | moderate form of osteogenesis imperfecta caused by compound heterozygous lepre1 mutations |
| url | http://www.sciencedirect.com/science/article/pii/S2352187218300494 |
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