CAJ | 학술논문

目的分析一先天性手足裂伴并指／趾畸形家系的临床表现,并从分子水平查找致病原因,为罹患家庭提供遗传咨询.方法通过X线检查资料及手足裂外观照片,对家系3代现存3例患者(共4例患者)进行临床分析,对3例患者用常规方法制备外周血淋巴细胞染色体标本,进行G显带核型分析.从7名家系成员(包含3例患者)外周血样品中提取基因组DNA.针对p63基因全部15个外显子及WNT10b基因5个外显子进行引物设计合成、PCR扩增、回收纯化并测序.结果家系中现存3名患者均表现为双手中央分裂,其中1例患者双足呈楔形裂开,2例患者右足均为第3、4趾并指,皮肤黏连;G显带核型分析未发现染色体畸变;p63基因未检测到突变,WNT10b基因的外显子5a中发现一个碱基突变c.1058C＞T.结论通过家系内患者临床表型分析,可将该疾病类型确定为非综合征手足裂畸形,且临床症状逐代加重.测序结果提示p63基因和WNT10b基因关键区域内的点突变都不是引起该家系手足裂畸形的原因.
목적 분석일선천성수족렬반병지／지기형가계적림상표현,병종분자수평사조치병원인,위리환가정제공유전자순.방법 통과X선검사자료급수족렬외관조편,대가계3대현존3례환자(공4례환자)진행림상분석,대3례환자용상규방법제비외주혈림파세포염색체표본,진행G현대핵형분석.종7명가계성원(포함3례환자)외주혈양품중제취기인조DNA.침대p63기인전부15개외현자급WNT10b기인5개외현자진행인물설계합성、PCR확증、회수순화병측서.결과 가계중현존3명환자균표현위쌍수중앙분렬,기중1례환자쌍족정설형렬개,2례환자우족균위제3、4지병지,피부점련;G현대핵형분석미발현염색체기변;p63기인미검측도돌변,WNT10b기인적외현자5a중발현일개감기돌변c.1058C＞T.결론 통과가계내환자림상표형분석,가장해질병류형학정위비종합정수족렬기형,차림상증상축대가중.측서결과제시p63기인화WNT10b기인관건구역내적점돌변도불시인기해가계수족렬기형적원인.
Objective To identify the clinical symptoms and find the pathogeny of split-hand/ split-foot malformation (SHFM) for a Chinese family.Methods Three out of four affected patients in one three-generation Chinese pedigree SHFM family were examined of the malformed hands and feet observation by digital photographs and X-ray.Peripheral blood samples were collected from three affected patients followed by lymphocytes G banding assay.Genomic DNA was extracted from the whole blood samples of 7 available family members,including the three affected patients.All 15 exons of the p63 and 5 exons of the WNT10b were amplified by polymerase chain reaction (PCR) and followed by purification and gene sequencing.Results All three existing affected patients showed absence of the third radial fingers in their hands,one affected patient had a deep central cleft and central ray deficiency in his feet,and two affected patients had a soft-tissue syndactyly between the 3rd and 4th toes of the right foot.G banding assay showed that normal karyotypes in the three affected patients and invisible cytogenetic abnormality was found.Moreover,no mutation was found in the coding region of p63 gene.However,a mutation from C to T was oberserved at the exon 5 a in WNT10b gene (c.1058 C ＞ T).Conclusion This case is a rare condition characterized by non-syndromic SHFM and the phenotype got worse with the generations.In the current study,we concluded that the point mutation of gene p63 and WNT10b may not the cause of nonsyndromic SHFM in this family.