How High Are Carrier Frequencies of Rare Recessive Syndromes? Contemporary Estimates for Fanconi Anemia in the United States and Israel

被引:87
作者
Rosenberg, Philip S. [1 ]
Tamary, Hannah [2 ]
Alter, Blanche P. [3 ]
机构
[1] NCI, Biostat Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA
[2] Schneider Childrens Med Ctr Israel, Dept Pediat Hematol Oncol, Petah Tiqwa, Israel
[3] NCI, Clin Genet Branch, Div Canc Epidemiol & Genet, NIH,Dept Hlth & Human Serv, Rockville, MD 20852 USA
关键词
epidemiologic methods; Fanconi anemia; gene frequency; prevalence; SOUTH-AFRICA; CANCER INCIDENCE; APLASTIC-ANEMIA; HIGH PREVALENCE; BLOOM-SYNDROME; ETHNIC-ORIGIN; GROUP-A; MUTATION; POPULATION; DISEASE;
D O I
10.1002/ajmg.a.34087
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
For many recessive genetic syndromes, carrier frequencies have been assessed through screening studies in founder populations but remain unclear in heterogeneous populations. One such syndrome is Fanconi Anemia (FA). FA is a model disease in cancer research, yet there are no contemporary data on carrier frequency or prevalence in the general United States (US) population or elsewhere. We inferred carrier frequency from birth incidence using the Hardy-Weinberg law. We estimated prevalence using birth incidence and survival data. We defined "plausible ranges" to incorporate uncertainty about completeness of case ascertainment. We made estimates for the US and Israel using demographic data from the Fanconi Anemia Research Fund and Israeli Fanconi Anemia Registry. In the US, a plausible range for the carrier frequency is 1:156-1:209 [midpoint 1:181[; we estimate that 550-975 persons were living with FA in 2010. For Israel, a plausible range for the carrier frequency is 1:66-1:128 [midpoint 1:931 in line with founder screening studies; we estimate that 40-135 Israelis were living with FA in 2008. The estimated US FA carrier frequency of 1:181 is significantly higher than the historical estimate of 1:300; hence, the gap may be narrower than previously recognized between the US carrier frequency and higher carrier frequencies of around 1:100 in several founder groups including Ashkenazi Jews. Assessment of cancer risks in heterozygous carriers merits further study. Clinical trials in FA will require co-ordination and innovative design because the number of living US patients is probably less than 1,000. Published 2011 Wiley-Liss, Inc.
引用
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页码:1877 / 1883
页数:7
相关论文
共 46 条
[1]  
Altay C, 1997, CLIN GENET, V51, P296
[2]   Malignancies and survival patterns in the National Cancer Institute inherited bone marrow failure syndromes cohort study [J].
Alter, Blanche P. ;
Giri, Neelam ;
Savage, Sharon A. ;
Peters, June A. ;
Loud, Jennifer T. ;
Leathwood, Lisa ;
Carr, Ann G. ;
Greene, Mark H. ;
Rosenberg, Philip S. .
BRITISH JOURNAL OF HAEMATOLOGY, 2010, 150 (02) :179-188
[3]   Cancer in dyskeratosis congenita [J].
Alter, Blanche P. ;
Giri, Neelam ;
Savage, Sharon A. ;
Rosenberg, Philip S. .
BLOOD, 2009, 113 (26) :6549-6557
[4]   Cancer in Fanconi anemia, 1927-2001 [J].
Alter, BP .
CANCER, 2003, 97 (02) :425-440
[5]  
Alter BP, 2003, NATHAN OSKIS HEMATOL, P280
[6]  
[Anonymous], 1997, PRINCIPLES POPULATIO
[7]  
[Anonymous], 1993, INTRO BOOTSTRAP
[8]   Fanconi anemia and its diagnosis [J].
Auerbach, Arleen D. .
MUTATION RESEARCH-FUNDAMENTAL AND MOLECULAR MECHANISMS OF MUTAGENESIS, 2009, 668 (1-2) :4-10
[9]   Genetic heterogeneity among Fanconi anemia heterozygotes and risk of cancer [J].
Berwick, Marianne ;
Satagopan, Jaya M. ;
Ben-Porat, Leah ;
Carlson, Ann ;
Mah, Katherine ;
Henry, Rashida ;
Diotti, Raffaella ;
Milton, Kelly ;
Pujara, Kanan ;
Landers, Tom ;
Batish, Sat Dev ;
Morales, Jose ;
Schindler, Detlev ;
Hanenberg, Helmut ;
Hromas, Robert ;
Levran, Orna ;
Auerbach, Arleen D. .
CANCER RESEARCH, 2007, 67 (19) :9591-9596
[10]   Fanconi anemia in Tunisia:: high prevalence of group A and identification of new FANCA mutations [J].
Bouchlaka, C ;
Abdelhak, S ;
Amouri, A ;
Ben Abid, H ;
Hadiji, S ;
Frikha, M ;
Ben Othman, T ;
Amri, F ;
Ayadi, H ;
Hachicha, M ;
Rebaï, A ;
Saad, A ;
Dellagi, K .
JOURNAL OF HUMAN GENETICS, 2003, 48 (07) :352-361