Arman M Niknafs, Neelam Giri, Marena R Niewisch, Sharon A Savage
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Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. 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引用次数: 0
摘要
无血管坏死(AVN)和轻微创伤性骨折(MTF)在端粒生物学紊乱(TBDs)患者中引起显著的发病率。由于端粒功能和维持所必需的基因的致病性种系变异,tbd与骨髓衰竭、肺纤维化、癌症和许多其他并发症的高风险相关。了解AVN和MTF在tbd中发生的程度,并确定端粒在骨生物学中的作用需要更多研究的领域。我们评估了233例tbd患者AVN和MTF的发生情况。采用年龄、性别和基因匹配的TBD患者对照组来评估AVN/MTF与临床特征之间的关系。42例(18%)TBD患者出现至少一次AVN和/或MTF事件,其中19例患者在儿童期首次出现AVN和/或MTF事件。AVN和MTF在常染色体或x连锁隐性或杂合性TINF2疾病患者中最常见(19/36 AVN和17/19 MTF)。与对照组相比,雄激素和皮质类固醇在AVN患者中更常见(41.2% vs. 16.3%, p
Avascular Necrosis and Minimal Trauma Fractures in Telomere Biology Disorders.
Avascular necrosis (AVN) and minimal trauma fractures (MTF) cause significant morbidity in patients with telomere biology disorders (TBDs). TBDs are associated with very high risks of bone marrow failure, pulmonary fibrosis, cancer, and many other complications due to pathogenic germline variants in genes essential for telomere function and maintenance. To understand the extent to which AVN and MTF occur in TBDs and identify areas requiring more research in the role of telomeres in bone biology. We assessed the occurrence of AVN and MTF in 233 patients with TBDs. An age, gender, and gene-matched TBD patient control group was used to assess associations between AVN/MTF and clinical characteristics. Forty-two (18%) patients with TBD developed at least one AVN and/or MTF event with 19 patients experiencing their first event in childhood. AVN and MTF were most common in patients with autosomal or X-linked recessive, or heterozygous TINF2 disease (19/36 AVN and 17/19 MTF). Androgen and corticosteroid use were more common in patients with AVN compared with matched patient controls (41.2% vs. 16.3%, p < 0.05 and 41.2% vs. 14%, p < 0.01, respectively); however, 57.1% of patients experienced AVN and/or MTF events in the absence of androgen or corticosteroid use. Severe bone marrow failure and hematopoietic cell transplantation history were significantly more common in MTF patients than in controls (44.2% and 30.2% respectively, p < 0.05). There were no statistically significant associations between low bone mineral density or vitamin D deficiency and AVN or MTF. AVN and MTFs are common, debilitating complications in TBDs and frequently occur independently of androgen or corticosteroid use. Our results underscore the need for disease-specific translational studies as well as improved prevention and therapeutic options for patients with TBDs. Trial Registration: ClinicalTrials.gov identifier: NCT00027274.
期刊介绍:
Clinical Genetics links research to the clinic, translating advances in our understanding of the molecular basis of genetic disease for the practising clinical geneticist. The journal publishes high quality research papers, short reports, reviews and mini-reviews that connect medical genetics research with clinical practice.
Topics of particular interest are:
• Linking genetic variations to disease
• Genome rearrangements and disease
• Epigenetics and disease
• The translation of genotype to phenotype
• Genetics of complex disease
• Management/intervention of genetic diseases
• Novel therapies for genetic diseases
• Developmental biology, as it relates to clinical genetics
• Social science research on the psychological and behavioural aspects of living with or being at risk of genetic disease