CAJ | 학술논문

目的分析进行性家族性肝内胆汁淤积症3型(PFIC3)临床表现、遗传学特点和基因突变特点.方法应用聚合酶链反应-直接测序方法对2例临床疑似PFIC3的中国患儿ABCB4基因的27个外显子及其侧翼序列进行突变检测,并对其家庭主要成员进行相应突变基因检测,收集临床资料分析.健康对照组为无血缘关系的健康儿童50例,男27例,女23例,均为汉族.结果 2例患儿主要表现为胆汁淤积、黄疸伴瘙痒、肝大,血清γ-谷氨酰转肽酶、胆汁酸升高.例1为ABCB4基因c.2489ins A和c.3143_3145 delGCAinsCC复合杂合突变,例2为c.966G ＞C(p.G319R)和c.3220G＞ A(p.G1074R)复合杂合突变,均为新发突变;2例患儿父母及例2弟弟均为突变基因携带者.结论发现了4种尚未见报道的ABCB4基因新突变,c.2489ins A/c.3143_3145delGCAinsCC突变可能与严重临床表型相关.
목적 분석진행성가족성간내담즙어적증3형(PFIC3)림상표현、유전학특점화기인돌변특점.방법 응용취합매련반응-직접측서방법대2례림상의사PFIC3적중국환인ABCB4기인적27개외현자급기측익서렬진행돌변검측,병대기가정주요성원진행상응돌변기인검측,수집림상자료분석.건강대조조위무혈연관계적건강인동50례,남27례,녀23례,균위한족.결과 2례환인주요표현위담즙어적、황달반소양、간대,혈청γ-곡안선전태매、담즙산승고.례1위ABCB4기인c.2489ins A화c.3143_3145 delGCAinsCC복합잡합돌변,례2위c.966G ＞C(p.G319R)화c.3220G＞ A(p.G1074R)복합잡합돌변,균위신발돌변;2례환인부모급례2제제균위돌변기인휴대자.결론 발현료4충상미견보도적ABCB4기인신돌변,c.2489ins A/c.3143_3145delGCAinsCC돌변가능여엄중림상표형상관.
Objective To analyze the clinic and genetical characteristics of progressive familial intrahepatic cholestasis type 3 (PFIC3) of infancy caused by ATP binding cassette transporter A4 (ABCB4) gene mutation.Methods Clinical manifestations and laboratory test results of the 2 patients were summarized.Genomic DNA from peripheral blood was collected for genetic analysis in these patients.All fragments of exons of the ABCB4 gene of key members of the 2 families were amplified by polymerase chain reaction-sequence based typing method.Forward sequencing was performed for mutation analysis.Fifty unrelated individuals in Han population were healthy control group,male 27 cases,female 23 cases.Results The 2 patients had persistent intrahepatic cholestasis,jaundice with pruritus,hepatomegaly,and all showed elevated levels of serum gamma-glutamyl transpeptidase and bile acid.Two patients had ABCB4 gene mutations,which were novel mutations never reported before.A insertion mutation of c.2489insA in exon 21 combined with a mutation of c.3143_3145delGCAinsCC in exon 25,which was a compound heterozygous mutation,was identified in patient 1 ;A missense mutation of c.966G ＞ C (p.G319R) in exon 9 combined with a mutation of c.3220G ＞ A (p.G1074R) in exon 25,which was a compound heterozygous mutation,was identified in patient 2.All the parents and patient 2's younger brother were carriers of mutations.Conclusions Both two patients have novel ABCB4 gene mutations,c.2489insA/c.3143_3145delGCAinsCC might contributed to the serious clinical manifestation.