Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia.
Heterozygous Mutations in OAS1 Cause Infantile-Onset Pulmonary Alveolar Proteinosis with Hypogammaglobulinemia.
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DOI：
10.1016/j.ajhg.2018.01.019
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发表时间：
2018-03-01
影响因子：
9.8
通讯作者：
Ariga T
中科院分区：
文献类型：
--
作者：
Cho K;Yamada M;Agematsu K;Kanegane H;Miyake N;Ueki M;Akimoto T;Kobayashi N;Ikemoto S;Tanino M;Fujita A;Hayasaka I;Miyamoto S;Tanaka-Kubota M;Nakata K;Shiina M;Ogata K;Minakami H;Matsumoto N;Ariga T
肺泡蛋白沉积症(PAP)的特征是肺泡腔内表面活性物质积聚，并伴有低氧性呼吸衰竭。遗传性PAP(GPAP)是由肺泡II型上皮细胞表面活性蛋白编码基因或表面活性磷脂转运蛋白基因突变引起的。GPAP也是由基因突变引起的，这些基因的产物与肺泡巨噬细胞(AM)的表面活性物质分解代谢有关。我们对一家系进行了全外显子组序列分析，该家系患有婴儿起病的低丙种球蛋白血症，与PAP相关的基因SFTPB、SFTPC、ABCA3、CSF2RA、CSF2RB和GATA2没有致病突变。我们在三个患病的兄弟姐妹中发现了编码2，‘5’-寡腺苷合成酶1(OAS1)的OAS1杂合错义变异，但在未患病的家庭成员中未发现。下一代测序的深度序列分析显示，该变异在母亲外周血白细胞中的DNA嵌合率为3.81%，表明该家族中观察到的PAP可能是从母亲那里遗传的常染色体显性特征。我们在两个不相关的单纯性个体中发现了另外两个OAS1杂合错义变异，这些个体也表现为婴儿起病的PAP伴低丙种球蛋白血症。两个单纯性个体的PAP在造血干细胞移植后消失，表明OAS1功能障碍与AM缺陷导致的表面活性物质分解代谢受损有关。
Pulmonary alveolar proteinosis (PAP) is characterized by accumulation of a surfactant-like substance in alveolar spaces and hypoxemic respiratory failure. Genetic PAP (GPAP) is caused by mutations in genes encoding surfactant proteins or genes encoding a surfactant phospholipid transporter in alveolar type II epithelial cells. GPAP is also caused by mutations in genes whose products are implicated in surfactant catabolism in alveolar macrophages (AMs). We performed whole-exome sequence analysis in a family affected by infantile-onset PAP with hypogammaglobulinemia without causative mutations in genes associated with PAP: SFTPB, SFTPC, ABCA3, CSF2RA, CSF2RB, and GATA2. We identified a heterozygous missense variation in OAS1, encoding 2,′5′-oligoadenylate synthetase 1 (OAS1) in three affected siblings, but not in unaffected family members. Deep sequence analysis with next-generation sequencing indicated 3.81% mosaicism of this variant in DNA from their mother’s peripheral blood leukocytes, suggesting that PAP observed in this family could be inherited as an autosomal-dominant trait from the mother. We identified two additional de novo heterozygous missense variations of OAS1 in two unrelated simplex individuals also manifesting infantile-onset PAP with hypogammaglobulinemia. PAP in the two simplex individuals resolved after hematopoietic stem cell transplantation, indicating that OAS1 dysfunction is associated with impaired surfactant catabolism due to the defects in AMs.
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影响因子：
14.9
作者：
Schymkowitz J;Borg J;Stricher F;Nys R;Rousseau F;Serrano L
通讯作者：
Serrano L
影响因子：
6.5
作者：
Fitzgerald, Michael L.;Xavier, Ramnik;Freeman, Mason W.
通讯作者：
Freeman, Mason W.
影响因子：
5.8
作者：
Kosmider B;Messier EM;Janssen WJ;Nahreini P;Wang J;Hartshorn KL;Mason RJ
通讯作者：
Mason RJ
DOI：
10.1164/rccm.200406-716oc
发表时间：
2005-05-15
影响因子：
24.7
作者：
Tazawa, R;Hamano, E;Nukiwa, T
通讯作者：
Nukiwa, T
DOI：
10.1016/j.bbrc.2005.02.101
发表时间：
2005-04-22
影响因子：
3.1
作者：
Hamano, E;Hijikata, M;Keicho, N
通讯作者：
Keicho, N