中华医学遗传学杂志
中華醫學遺傳學雜誌
중화의학유전학잡지
CHINESE JOURNAL OF MEDICAL GENETICS
2015年
3期
327-330
,共4页
姜海鸥%葛传琴%王义旺%唐根云%全庆丽
薑海鷗%葛傳琴%王義旺%唐根雲%全慶麗
강해구%갈전금%왕의왕%당근운%전경려
USH2A基因%复合杂合性突变%Usher综合征
USH2A基因%複閤雜閤性突變%Usher綜閤徵
USH2A기인%복합잡합성돌변%Usher종합정
USH2A gene%Compound heterozygous mutations%Usher syndrome
目的 鉴定1个Usher综合征2型家系USH2A基因的致病性突变,为其提供分子遗传学依据.方法 对1个Usher综合征家系2例患者与4名表型正常家系成员的USH2A基因的全部编码区及侧翼剪切位点进行PCR扩增,产物直接测序进行突变分析,同时选择100名无亲缘关系的正常对照进行检测.结果 家系中2例患者(先证者及其妹妹)均携带了USH2A基因第42外显子c.8272G＞T(p.E2758X)和第63外显子c.12376-12378 ACT＞TAA(p.T4126X)复合杂合性突变.而患者的父亲为c.12376-12378 ACT＞TAA杂合突变携带者,其母亲为c.8272G＞T杂合突变携带者,两名表型正常的家系成员未检测到突变.经检索HGMD数据库两个突变均为新突变,且与家系疾病表型共分离.100名无血缘关系的正常人中未发现该突变.结论 USH2A基因的c.8272G＞T(p.E2758X)和c.1237612378ACT＞TAA(p.T4126X)复合杂合性突变可能为该家系的致病原因,为该Usher综合征家系的病因诊断提供了分子遗传学依据.
目的 鑒定1箇Usher綜閤徵2型傢繫USH2A基因的緻病性突變,為其提供分子遺傳學依據.方法 對1箇Usher綜閤徵傢繫2例患者與4名錶型正常傢繫成員的USH2A基因的全部編碼區及側翼剪切位點進行PCR擴增,產物直接測序進行突變分析,同時選擇100名無親緣關繫的正常對照進行檢測.結果 傢繫中2例患者(先證者及其妹妹)均攜帶瞭USH2A基因第42外顯子c.8272G＞T(p.E2758X)和第63外顯子c.12376-12378 ACT＞TAA(p.T4126X)複閤雜閤性突變.而患者的父親為c.12376-12378 ACT＞TAA雜閤突變攜帶者,其母親為c.8272G＞T雜閤突變攜帶者,兩名錶型正常的傢繫成員未檢測到突變.經檢索HGMD數據庫兩箇突變均為新突變,且與傢繫疾病錶型共分離.100名無血緣關繫的正常人中未髮現該突變.結論 USH2A基因的c.8272G＞T(p.E2758X)和c.1237612378ACT＞TAA(p.T4126X)複閤雜閤性突變可能為該傢繫的緻病原因,為該Usher綜閤徵傢繫的病因診斷提供瞭分子遺傳學依據.
목적 감정1개Usher종합정2형가계USH2A기인적치병성돌변,위기제공분자유전학의거.방법 대1개Usher종합정가계2례환자여4명표형정상가계성원적USH2A기인적전부편마구급측익전절위점진행PCR확증,산물직접측서진행돌변분석,동시선택100명무친연관계적정상대조진행검측.결과 가계중2례환자(선증자급기매매)균휴대료USH2A기인제42외현자c.8272G＞T(p.E2758X)화제63외현자c.12376-12378 ACT＞TAA(p.T4126X)복합잡합성돌변.이환자적부친위c.12376-12378 ACT＞TAA잡합돌변휴대자,기모친위c.8272G＞T잡합돌변휴대자,량명표형정상적가계성원미검측도돌변.경검색HGMD수거고량개돌변균위신돌변,차여가계질병표형공분리.100명무혈연관계적정상인중미발현해돌변.결론 USH2A기인적c.8272G＞T(p.E2758X)화c.1237612378ACT＞TAA(p.T4126X)복합잡합성돌변가능위해가계적치병원인,위해Usher종합정가계적병인진단제공료분자유전학의거.
Objective To identify potential mutations in a Chinese family with Usher syndrome type Ⅱ.Methods Genomic DNA was obtained from two affected and four unaffected members of the family and subjected to amplification of the entire coding sequence and splicing sites of USH2A gene.Mutation detection was conducted by direct sequencing of the PCR products.A total of 100 normal unrelated individuals were used as controls.Results The patients were identified to be a compound heterozygote for two mutations:c.8272G＞T (p.E2758X) in exon 42 from his mother and c.12376-12378ACT＞TAA (p.T4126X) in exon 63 of the USH2A gene from his father.Both mutations were not found in either of the two unaffected family members or 100 unrelated controls,and had completely co segregated with the disease phenotype in the family.Neither mutation has been reported in the HGMD database.Conclusion The novel compound heterozygous mutations c.8272G＞T and c.12376-12378ACT＞TAA within the USH2A gene may be responsible for the disease.This result may provide new clues for molecular diagnosis of this disease.
