CAJ | 학술논문

目的研究3个以血液学改变为首发临床表现的植物固醇血症先证者及家系的临床表型和基冈诊断.方法光学显微镜观察红细胞及血小板的形态;高效液相色谱法检测血浆中豆固醇、二氢胆固醇及谷固醇的含量;PCR法扩增先证者ABCG5和ABCG8基因外显子和侧翼序列,针对先证者的突变位点,对其家系成员进行相应片段基因的检测;同时在正常人群中筛查以排除多态性.结果巨大血小板、溶血性贫血、脾脏肿大及黄褐瘤是患者共同的表现.外周血涂片可见异形红细胞,如口形红细胞增多,血小板体积增大甚至达红细胞大小;血浆中植物固醇尤其是谷固醇的含量显著增高,是正常人30倍左右;基因分析发现4个突变:ABCG5 C20896T(R446X)、A20883G,ABCG8del43683-43724、del43866C-43867G/ins43866T,后3个是新的突变位点.结论伴有巨大血小板和溶血性贫血的植物固醇血症是植物固醇血症一个特殊的亚型.对不能解释的巨大血小板,尤其是伴有溶血或(和)口形红细胞的患者应考虑植物固醇血症的可能.
목적 연구3개이혈액학개변위수발림상표현적식물고순혈증선증자급가계적림상표형화기강진단.방법 광학현미경관찰홍세포급혈소판적형태;고효액상색보법검측혈장중두고순、이경담고순급곡고순적함량;PCR법확증선증자ABCG5화ABCG8기인외현자화측익서렬,침대선증자적돌변위점,대기가계성원진행상응편단기인적검측;동시재정상인군중사사이배제다태성.결과 거대혈소판、용혈성빈혈、비장종대급황갈류시환자공동적표현.외주혈도편가견이형홍세포,여구형홍세포증다,혈소판체적증대심지체홍세포대소;혈장중식물고순우기시곡고순적함량현저증고,시정상인30배좌우;기인분석발현4개돌변:ABCG5 C20896T(R446X)、A20883G,ABCG8del43683-43724、del43866C-43867G/ins43866T,후3개시신적돌변위점.결론 반유거대혈소판화용혈성빈혈적식물고순혈증시식물고순혈증일개특수적아형.대불능해석적거대혈소판,우기시반유용혈혹(화)구형홍세포적환자응고필식물고순혈증적가능.
Objective To study the clinical features and ABCG5/ABCG8 gene mutations of three pedigrees of phytosterolemia presented with macrothrombocytopenia and hemolysis. Methods Erythrocyte and platelet morphology were examined under light microscope. Plasma sterol levels were measured by high pressure/performance liquid chromatography method. All of ABCG5 and ABCG8 exons and intron-exon boundaries were directly sequenced to identify mutations, the corresponding gene mutation sites of three families members and healthy individuals were detected. Results All the patients presented macrothrombocytopenia , hemolysis, splenomegaly and xanthomas. The blood smears showed large platelets, some as large as erythrocytes, and abnormal erythrocyte shapes, such as stomatocytes. Plasma concentrations of phytosterols,especially sitosterol were markedly elevated (30 fold) in the affected patients. Four mutations were identified in these three pedigrees, ABCG5 C20896T ( R446X) and A20883G , ABCG8 del43683-43724 and del1938C-1939G/ins1938T. The latter three were novel mutations reported for the first time. Conclusions Phytosterolemia associated with macrothrombocytopenia and hemolysis is a new subtype of this disease. Plasma phytosterols and related gene analysis should be performed when ever an unexplained macrothrombocytopenia, especially combined with haemolysis or/and stomatocytosis.