Chorea-acanthocytosis: genetic linkage to chromosome 9q21.
Chorea-acanthocytosis: genetic linkage to chromosome 9q21.
复制标题
舞蹈病-棘红细胞增多症：与染色体 9q21 的遗传连锁。
DOI：
10.1086/514876
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发表时间：
1997
影响因子：
9.8
通讯作者：
Monaco,AP
中科院分区：
文献类型：
--
作者：
Rubio,JP;Danek,A;Stone,C;Chalmers,R;Wood,N;Verellen,C;Ferrer,X;Malandrini,A;Fabrizi,GM;Manfredi,M;Vance,J;Pericak-Vance,M;Brown,R;Rudolf,G;Picard,F;Alonso,E;Brin,M;Németh,AH;Farrall,M;Monaco,AP
舞蹈病-棘红细胞增多症 (CHAC) 是一种罕见的常染色体隐性遗传疾病，其特征是进行性神经变性和异常的红细胞形态（棘红细胞增多症），发病于三至五十岁。棘红细胞增多症（神经棘红细胞增多症）引起的神经功能障碍也见于无β脂蛋白血症和 X 连锁麦克劳德综合征。尽管 McLeod 综合征的分子病因学已被定义（Ho 等人，1994），但 CHAC 的分子病因学仍不清楚。在没有细胞遗传学重排的情况下，我们启动了全基因组扫描，寻找 11 个家族的连锁关系，分离出具有不同地理起源的 CHAC。我们在这里报告，在所有家族中，该疾病都与染色体 9q21 的 6 cM 区域相关，该区域两侧是重组标记 GATA89a11 和 D9S1843。 D9S1867 的最大两点 LOD 得分为 7.1 (θ = .00)，并且在近交家族的后代中，连锁区域已通过血统纯合性得到证实。这些发现为 CHAC 单一基因座的参与提供了强有力的证据，并且是疾病基因定位克隆的第一步。
Chorea-acanthocytosis (CHAC) is a rare autosomal recessive disorder characterized by progressive neurode-generation and unusual red-cell morphology (acantho-cytosis), with onset in the third to fifth decade of life. Neurological impairment with acanthocytosis (neuro-acanthocytosis) also is seen in abetalipoproteinemia and X-linked McLeod syndrome. Whereas the molecular etiology of McLeod syndrome has been defined (Ho et al. 1994), that of CHAC is still unknown. In the absence of cytogenetic rearrangements, we initiated a genomewide scan for linkage in 11 families, segregating for CHAC, who are of diverse geographical origin. We report here that the disease is linked, in all families, to a 6-cM region of chromosome 9q21 that is flanked by the recombinant markers GATA89a11 and D9S1843. A maximum two-point LOD score of 7.1 (θ = .00) for D9S1867 was achieved, and the linked region has been confirmed by homozygosity-by-descent, in offspring from inbred families. These findings provide strong evidence for the involvement of a single locus for CHAC and are the first step in positional cloning of the disease gene.