Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase

被引:133
作者
Parry, Erin M. [1 ,2 ,3 ]
Alder, Jonathan K. [1 ,2 ]
Qi, Xiaodong [4 ]
Chen, Julian J. -L. [5 ,6 ]
Armanios, Mary [1 ,2 ,4 ]
机构
[1] Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
[2] Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA
[3] Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD 21287 USA
[4] Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA
[5] Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA
[6] Arizona State Univ, Sch Life Sci, Tempe, AZ USA
关键词
DOMINANT DYSKERATOSIS-CONGENITA; APLASTIC-ANEMIA; REVERSE-TRANSCRIPTASE; CELL TRANSPLANTATION; MUTATIONS; DISEASE; RNA; ANTICIPATION; COMPONENT; FAMILIES;
D O I
10.1182/blood-2010-11-322149
中图分类号
R5 [内科学];
学科分类号
1002 ; 100201 ;
摘要
Mutations in the essential telomerase components hTERT and hTR cause dyskeratosis congenita, a bone marrow failure syndrome characterized by mucocutaneous features. Some (similar to 3%) sporadic aplastic anemia (AA) and idiopathic pulmonary fibrosis cases also carry mutations in hTERT and hTR. Even though it can affect clinical outcome, because the mutation frequency is rare, genetic testing is not standard. We examined whether the cooccurrence of bone marrow failure and pulmonary fibrosis in the same individual or family enriches for the presence of a telomerase mutation. Ten consecutive individuals with a total of 36 family members who fulfilled these criteria carried a germline mutant telomerase gene (100%). The mean age of onset for individuals with AA was significantly younger than that for those with pulmonary fibrosis (14 vs 51; P<.0001). Families displayed autosomal dominant inheritance and there was an evolving pattern of genetic anticipation, with the older generation primarily affected by pulmonary fibrosis and successive generations by bone marrow failure. The cooccurrence of AA and pulmonary fibrosis in a single patient or family is highly predictive for the presence of a germline telomerase defect. This diagnosis affects the choice of bone marrow transplantation preparative regimen and can prevent morbidity. (Blood. 2011; 117(21): 5607-5611)
引用
收藏
页码:5607 / 5611
页数:5
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