Gazda H, Lipton J M, Willig T N, Ball S, Niemeyer C M, Tchernia G, Mohandas N, Daly M J, Ploszynska A, Orfali K A, Vlachos A, Glader B E, Rokicka-Milewska R, Ohara A, Baker D, Pospisilova D, Webber A, Viskochil D H, Nathan D G, Beggs A H, Sieff C A
Division of Pediatric Hematology and Oncology, Dana Farber Cancer Institute and Children's Hospital, Boston, Massachusetts 02115, USA.
Blood. 2001 Apr 1;97(7):2145-50. doi: 10.1182/blood.v97.7.2145.
Diamond-Blackfan anemia (DBA) is a rare congenital hypoplastic anemia that usually presents early in infancy and is inherited in 10% to 20% of cases. Linkage analysis has shown that DBA in many of both dominant and recessive DBA families mapped to chromosome 19q13.2 leading to the cloning of a gene on chromosome 19q13.2 that encodes a ribosomal protein, RPS19. However, subsequently, mutations of the RPS19 gene have only been identified in 25% of all patients with DBA. This study analyzed 14 multiplex DBA families, 9 of which had 19q13.2 haplotypes inconsistent with 19q linkage. A genome-wide search for linked loci suggested the presence of a second DBA locus in a 26.4-centimorgan (cM) interval on human chromosome 8p. Subsequently, 24 additional DBA families were ascertained and all 38 families were analyzed with additional polymorphic markers on chromosome 8p. In total, 18 of 38 families were consistent with linkage to chromosome 8p with a maximal LOD score with heterogeneity of 3.55 at D8S277 assuming 90% penetrance. The results indicate the existence of a second DBA gene in the 26.4-cM telomeric region of human chromosome 8p23.3-p22, most likely within an 8.1-cM interval flanked by D8S518 and D8S1825. Seven families were inconsistent with linkage to 8p or 19q and did not reveal mutations in the RPS19 gene, suggesting further genetic heterogeneity. (Blood. 2001;97:2145-2150)
钻石黑范贫血（DBA）是一种罕见的先天性再生障碍性贫血，通常在婴儿早期发病，10%至20%的病例为遗传性。连锁分析表明，许多显性和隐性DBA家族中的DBA基因定位于19号染色体长臂1区3带2亚带（19q13.2），从而导致在19q13.2上克隆出一个编码核糖体蛋白RPS19的基因。然而，随后在所有DBA患者中仅发现25%存在RPS19基因突变。本研究分析了14个多位点DBA家族，其中9个家族的19q13.2单倍型与19q连锁不一致。全基因组连锁位点搜索提示在人类8号染色体短臂（8p）上26.4厘摩（cM）区间存在第二个DBA位点。随后，又确定了另外24个DBA家族，并使用8号染色体短臂上的其他多态性标记对所有38个家族进行分析。总共38个家族中有18个与8号染色体短臂连锁一致，假设外显率为90%时，在D8S277处的最大异质性对数优势（LOD）评分为3.55。结果表明在人类8号染色体短臂2区3带至2区2带（8p23.3 - p22）的26.4 - cM端粒区域存在第二个DBA基因，最有可能位于D8S518和D8S1825侧翼的8.1 - cM区间内。7个家族与8号染色体短臂或19号染色体长臂连锁不一致，且未发现RPS19基因突变，提示存在进一步的遗传异质性。（《血液》. 2001年；97卷：2145 - 2150页）
