2型糖尿病家系发病特征与危险因素初步调查

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

2型糖尿病家系发病特征与危险因素初步调查

目的 对2型糖尿病家系中的遗传特征、危险因素进行调查分析,为系统研究2型糖尿病及制定干预措施提供依据.方法 根据1997年美国糖尿病学会(ADA)标准,利用口服葡萄糖耐量试验确诊糖尿病,根据胰岛素功能测定和血清谷氨酸脱羧酶抗体(GADAb)、胰岛细胞抗体(ICA)和胰岛素自身抗体(IAA)检测及临床特征排除1型糖尿病,根据遗传特征及临床特点排除年轻的成年发病型糖尿病(MODY),根据母系遗传伴耳聋等临床特征排除线粒体基因突变家系,最终筛选出2型糖尿病家系182个(实际调查865例)并进行分析.结果 182个家系中男女2型糖尿病患病率(男性42.59%、女性48.18%)、新诊断率(男性9.89%、女性1 1.82%)差异无统计学意义(P＞0.05).家系第1代277例患者发病年龄为(63.3±12.4)岁,其中男性为(64.4±12.5)岁,女性为(62.3±10.3)岁;第2代468例患者发病年龄为(47.1 ±8.7)岁,其中男性为(48.2±9.3)岁,女性为(46.1±8.1)岁;第3代120例患者发病年龄为(29.6±10.2)岁,其中男性为(28.9 ±9.5)岁,女性为(30.0±10.4)岁.新诊断2型糖尿病组、新诊断糖调节受损(IGR)组分别与非患病亲属组比较,高血压病史、高脂血症史、吸烟史、活动量差异均有统计学意义;5年前体重、1年前体重、目前体重、腰围、腰臀比差异也有统计学意义,股围差异无统计学意义.结论 2型糖尿病发病无性别差异.肥胖、高血压病、吸烟、高脂血症、活动量较少与2型糖尿病、IGR相关.活动量较多可能是家族中的非患病亲属及IGR患者较晚进入糖尿病期的原因之一.

Abstract：

Objective To explore the characteristics and risk factors of type 2 diabetes mellitus (T2DM) onset in pedigrees. Methods A total of 865 subjects were screened and diagnosed by oral glucose tolerance test (OGTT) based on American Diabetes Association (ADA) criteria. Type 1 diabetes mellitus (T1DM) , maturity onset diabetes of the young (MODY) and chondriosome diabetes were excluded by clinical features and laboratory test of insulin and autoantibodies including glutamic acid decarboxylase antibody, insular cellular antibody and insulin autoantibody. A total of 182 pedigrees of T2DM were obtained. Results No gender difference was found in the prevalence of T2DM (42. 59% in male and 48. 18% in female respectively, P ＞0. 05) , nor was the newly diagnosed rate(9. 89% in male and 11. 82%in female, P ＞ 0. 05). The onset age was (63. 3 ± 12. 4) years old in the first generation [(64. 4 ± 12. 5)years in male and (62. 3 ± 10. 3) years in female] , (47. 1 ± 8. 7) years old in the second generation [(48. 2 ±9. 3)years in male and (46. 1 ± 8. 1) years in female] , (29. 6 ± 10. 2) years old in the third generation [(28. 9 ±9. 5)years in male and (30. 0 ± 10. 4)years in female]. Compared with normal glucose tolerance (NGT) subjects , newly diagnosed T2DM and impaired glucose regulation (IGR) subjects had higher prevalence of hypertension, hyperlipidemia and smoking but less physical activities. Statistical differences were shown in body weight five years before diagnosis, one years before diagnosis and at diagnosis in newly diagnosed T2DM[(68. 4 ±12. 4)kg, (69. 5 ± 11. 0)kg and (69. 1 ±9. 6)kg] and IGR[(66. 1 ±10.7)kg, (65.9 ± 10.7) kg and(65.7 ± 10.4) kg] , when compared with NGT [(61.0 ± 10.2) kg,(59. 5 ±11.0) kg and (60. 1 ± 10. 4) kg, all P ＜ 0. 05] . The same results were obtained with waist circumference and waist-hip ratio [(4. 1 ± 12. 5) cm and 0. 92 ± 0. 36 in newly diagnosed T2DM while (89. 1 ± 10. 7) cm and 0. 90 ± 0. 64 in IGR] , when compared with NGT[(82. 5 ± 10. 1) cm and 0. 82 ±0. 25] , all P ＜0. 05. Conclusions No gender difference was found in the onset characteristics of T2DM.High prevalence of obesity, hypertension, hyperlipidemia and smoking with less physical activities were associated with T2DM.     

两个肢带型肌营养不良2D型家系SGCA基因遗传分析和产前诊断

目的对中国汉族肢带型肌营养不良2D(limb-girdle muscular dystrophy type 2D,LGMD2D)型的2个家系进行SGCA基因分析,明确病因并在此基础上为该家系中的胎儿进行产前诊断,提供遗传咨询与指导。方法回顾性收集2017年6月至2018年1月在郑州大学第一附属医院就诊的2个LGMD2D型家系,提取先证者和其父母的外周血,通过探针杂交技术对先证者LGMD相关21个基因编码区及其侧翼序列进行高通量测序,进一步采用Sanger测序和/或荧光定量聚合酶链反应对先证者父母目标基因区域进行检测,同时验证变异来源;明确先证者病因后,进一步对家系中胎儿进行产前诊断。结果家系1:先证者存在SGCA基因c.218C>G(p.P73R)和c.101G>A(p.R34H)复合杂合变异;产前诊断结果显示,胎儿与先证者一样同时遗传了父母双方的致病变异,胎儿父母选择终止妊娠。家系2:先证者携带SGCA基因c.218C>T(p.P73L)和该基因第7和第8外显子杂合缺失复合杂合变异,但胎儿不携带上述两变异,家属选择继续妊娠。胎儿足月分娩,随访至2岁,肌酶谱、体格、运动和智力发育均未见异常。结论SGCA基因复合杂合突变是2个LGMD2D型家系的致病原因,其中c.218C>G(p.P73R)、c.218C>T(p.P73L)为尚未报道的新突变。基于高通量测序可快速、准确地对该病进行基因诊断和产前诊断。     

罕见基因型的肝豆状核变性姐妹及其家系报告

<正>肝豆状核变性（hepatolenticular degeneration, HLD）又称Wilson病，是一种由染色体13q14.3上ATP7B基因突变引起铜代谢障碍的常染色体隐性遗传疾病。目前已报道的ATP7B基因致病变异多达900余种，HLD的临床表现多种多样，最常见的包括肝脏和神经系统相关症状。本病在世界范围的患病率为1/2600～1/30 000,携带者频率约为1/90^[1-3]。虽然该病的发病率低，     

先天性白内障一家系中两个β-晶体蛋白基因的突变筛查

目的对一中国常染色体显性先天性粉尘状白内障家系进行β-晶体蛋白基因(cryba1、crybb1)的突变筛查。方法对一中国先天性白内障家系进行研究,通过直接测序,筛查此家系中全部患者的cryba1基因、crybb1基因外显子以及临近的内含子的剪接位点。结果直接测序后发现该粉尘状白内障家系cryba1基因和crybb1基因的外显子及其临近的内含子中,均未发现任何突变。结论该表型的先天性白内障家系并非是由这两个β-晶体蛋白基因突变引起。     

α地中海贫血HKαα／--SEA基因型家系分析

目的：研究巢式 PCR 结合家系分析的方法对罕见α地中海贫血（α地贫）的诊断价值。方法对先证者及12名家系成员,采用血常规分析、红细胞脆性及血红蛋白电泳进行地贫筛查;采用 PCR-反向斑点杂交（ PCR-reverse dot blot , RDB ）技术诊断非缺失α地贫点突变和17种β地贫基因点突变;采用跨越断裂点聚合酶链反应（ Gap-PCR ）进行缺失型α地贫基因型分析;采用巢式 PCR 检测 HKαα基因型;绘制α地贫基因遗传图谱。结果12例家系成员中,4例 MCV、MCH、红细胞脆性低于正常参考值,8例血液学指标均无异常;12例血红蛋白电泳均正常;12例家系成员中--SEA／αα和αα／αα基因型各2例, HKαα／αα基因型6例, HKαα／--SEA基因型2例;均无17种常见β地贫和3种常见非缺失α地贫。结论巢式PCR 结合家系分析方法是发现罕见地贫基因型并减少HKαα地贫的漏诊误诊的重要方法。     

遗传性肾炎1例及其家系调查

患者男 ,18岁。因“反复颜面浮肿伴听力及视力下降 2年”于 1999年 11月 1日入院。患者近 2年来反复出现颜面浮肿 ,无少尿及高血压 ,无发热、尿频、尿急、尿痛 ,伴有听力及视力下降 ,尤以听力下降明显。当地医院尿常规检查 :尿蛋白 ( )～ ( ) ,红细胞( )～ ( ) ,无管型。 2 0ｄ前因“受凉感冒”后再次出现颜面浮肿 ,予肌注青霉素 80万Ｕ ,每日 2次 ,疗效差 ,颜面浮肿加重 ,尿量偏少 ,伴纳差、乏力 ,时有鼻出血 ,为进一步诊治而来我院。家族史 :患者 3个兄长曾分别在广州某医院及当地医院诊为“慢性肾炎、肾功衰竭、尿毒症” ,已先后…     

遗传性乳光牙本质病的家系调查及修复方法

目的:了解遗传性乳光牙本质(又名牙本质发育不全Ⅱ型,DGI-Ⅱ)的遗传特征,探讨其治疗方法。方法:调查在上海发现的1例遗传性乳光牙本质患者的家系成员,进行系谱分析。对先证者作金瓷修复体治疗,并调查该家系受累者的修复情况。结果:该遗传性乳光牙本质家系中,患者连续5代出现,子代患病率接近50%。该家系子代义齿修复率90%,修复方式包括金瓷修复体和可摘局部义齿,以金瓷修复体为主,修复后美观和咀嚼功能良好。结论:遗传性乳光牙本质家系发病率高,金瓷修复体能达到预防牙体磨损和崩裂、恢复美观和咀嚼功能的效果。     

一视紫红质基因突变常染色体显性遗传视网膜色素变性家系的临床特征及其与基因型的关系

视网膜色素变性(RP)是以夜盲、进行性视野损害、视网膜色素沉着、视盘呈蜡黄色萎缩和视网膜电图(ERG)呈熄灭型为主要临床特征的遗传性致盲眼病[1,2].RP遗传方式复杂,以常染色体显性遗传RP(ADRP)为多见[3].在已成功克隆出15个ADRP致病基因中,视紫红质(RHO)基因是引起ADRP的主要致病基因,大约20%的ADRP患者存在RHO基因突变[4-6].RHO突变位点很多,表型各异.为探讨RHO基因型与RP的关系,我们观察了1个RHO基因突变的ADRP家系中RP患者的临床特征.现将结果报道如下.     

一个X-连锁隐性遗传视网膜色素变性家系的RPGR基因新突变

目的 研究X-连锁隐性遗传视网膜色素变性(RP)家系RPGR基因突变男性患者和女性携带者的临床表型.方法 家系调查研究.收集RP先证者及其家系资料,完善眼科检查,抽取现存77名家系成员和80名正常对照者外周静脉血,提取DNA,进行聚合酶链反应(PCR),扩增RPGR基因外显子ORF15,扩增产物纯化后直接测序.结果 RP家系中,8例RP患者均为男性,呈隔代传递,不存在男性至男性的传递,患者的母亲及女儿都是致病基因携带者而不发病,符合X-连锁隐性遗传方式.在8例男性RP患者和14例女性致病基因携带者的RPGR基因外显子ORF15+577_578位点发现一个AG缺失突变,引起阅读框架的改变,该基因缺失突变在家系中共分离.AG缺失突变导致男性患者典型的RP改变,但发病时间和进展程度不一.携带有杂合型基因突变的14例女性携带者最具特征性的临床表型是中高度近视眼(-5.00～-22.00 D).结论 该RP家系患者由RPGR 基因外显子ORF15移码突变致g.ORF15+577_578delAG位点缺失.RPGR基因外显子ORF15的新突变可导致男性患者严重的RP表型,但女性致病基因携带者仅表现为中高度近视眼.(中华眼科杂志,2011,47:516-520)

Abstract：

Objective To screen the mutation in the RPGR gene in a large Chinese family with X-linked recessive retinitis pigmentosa (RP) and to describe the phenotype in affected males and female carriers. Methods Ophthalmic examinations were performed in 77 family members of a RP pedigree to identify affected individuals. Polymerase chain reaction (PCR) and direct sequencing were used for screening of mutations in RPGR gene exon ORF15. Results Mutation screening demonstrated a novel mutation, g.ORF15+577_ 578delAG, which caused an open reading frameshift and resulted in premature truncation of the RPGR protein. This mutation was detected in 8 affected male individuals and 14 obligate female carriers in this family and was found to segregate with the phenotype in this family. This mutation led to a severe RP phenotype in male affected individuals with some variability in the age of onset of night blindness and loss of visual acuity, but was recessive in female carriers without a RP phenotype. However the most striking phenotypic feature in female carriers in this pedigree was moderate to high myopia with refractive error ranging from -5.00 D to -22.00 D in 14 female carriers. Conclusions This novel mutation in RPGR ORF15 causes serious RP phenotype in males and no RP phenotype in female carriers. Moderate to high myopia was a particular feature for female carriers in this pedigree. Our finding expands the spectrum of RPGR mutations causing RP and phenotypic spectrum of the disease in Chinese family, which is useful for further genetic consultation and genetic diagnosis.