共 22 条
Syndrome complex of bone marrow failure and pulmonary fibrosis predicts germline defects in telomerase
被引:133
作者:

Parry, Erin M.
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机构:
Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA
Johns Hopkins Univ, Sch Med, Med Scientist Training Program, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

Alder, Jonathan K.
论文数: 0 引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

Qi, Xiaodong
论文数: 0 引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

Chen, Julian J. -L.
论文数: 0 引用数: 0
h-index: 0
机构:
Arizona State Univ, Dept Chem & Biochem, Tempe, AZ USA
Arizona State Univ, Sch Life Sci, Tempe, AZ USA Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA

Armanios, Mary
论文数: 0 引用数: 0
h-index: 0
机构:
Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
Johns Hopkins Univ, Sch Med, Sidney Kimmel Comprehens Canc Ctr, Baltimore, MD 21287 USA
Johns Hopkins Univ, Sch Med, McKusick Nathans Inst Genet Med, Baltimore, MD 21287 USA Johns Hopkins Univ, Sch Med, Dept Oncol, Baltimore, MD 21287 USA
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
来源:
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)
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收藏
页码:5607 / 5611
页数:5
相关论文
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