Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease
Evidence for linkage of familial Diamond-Blackfan anemia to chromosome 8p23.3-p22 and for non-19q non-8p disease
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DOI：
10.1182/blood.v97.7.2145
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发表时间：
2001-04-01
期刊：
影响因子：
20.3
通讯作者：
Sieff, CA
中科院分区：
文献类型：
--
作者：
Gazda, H;Lipton, JM;Sieff, CA
Diamond-Blackfan 贫血 (DBA) 是一种罕见的先天性发育不良性贫血，通常在婴儿早期出现，10% 至 20% 的病例是遗传性的。连锁分析表明，许多显性和隐性 DBA 家族中的 DBA 都映射到染色体 19q13.2，从而导致在染色体 19q13.2 上克隆一个编码核糖体蛋白 RPS19 的基因。然而，随后仅在所有 DBA 患者中发现了 25% 的 RPS19 基因突变。本研究分析了 14 个多重 DBA 家族，其中 9 个家族的 19q13.2 单倍型与 19q 连锁不一致。对连锁基因座的全基因组搜索表明，在人类染色体 8p 上 26.4 厘摩 (cM) 间隔内存在第二个 DBA 基因座。随后，确定了另外 24 个 DBA 家族，并使用 8p 染色体上的额外多态性标记对所有 38 个家族进行了分析。总共，38 个家族中的 18 个与染色体 8p 连锁一致，假设外显率为 90%，D8S277 的最大 LOD 评分异质性为 3.55。结果表明，在人类染色体 8p23.3-p22 的 26.4-cM 端粒区域中存在第二个 DBA 基因，最有可能在 D8S518 和 D8S1825 两侧的 8.1-cM 区间内。七个家族与 8p 或 19q 的连锁不一致，并且没有揭示 RPS19 基因的突变，这表明进一步的遗传异质性。 （血液。2001；97：2145-2150）(C) 2001 年，美国血液学会。
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) (C) 2001 by The American Society of Hematology.