22q11.2微缺失综合征的分子诊断及缺失范围检测

目的 分别采用多重连接探针扩增技术(MLPA)与荧光原位杂交技术(FISH)对22q1 1.2微缺失综合征外周血标本患者基因缺失/重复突变的类型及变异范围进行检测,分析在22q11.2微缺失综合征诊断中二者联合应用的诊断价值.方法 采集1例仅心脏异常患儿及其父母外周血,取200 μL外周血提取DNA后采用MLPA技术对患儿及其父母的染色体22q11.2缺失的范围进行检测,取外周血1 mL进行培养,采用DiGeorge/VCFS N25(D22S75)的FISH探针对培养后的中期淋巴细胞进行杂交.结果 患儿淋巴细胞分裂中期细胞应用FISH技术检测结果为22号染色体上的DiGeorge/VCFS N25(D22S75)区杂合性缺失;MLPA验证结果显示患儿与22q11.2微缺失综合征相关的6个探针对应的片段大小位置在3100的电泳图上荧光峰值相比健康对照明显出现减半,其父母亲均在正常范围.患儿的临床表现仅有先天性心脏病,无其他异常,与其基因缺失片段长度(2.0 Mb)极不相称.结论 联合应用FISH和MLPA检测22q11.2微缺失综合征,可以明显提高诊断的准确性.22q11.2微缺失综合征的临床表现与基因缺失片段的长度无相关性.     

17q12微缺失综合征3例报告并文献复习

目的 总结儿童染色体17q12微缺失综合征的临床特征，以提高对该病的认识。方法 回顾性分析2014年10月至2021年10月收治的3例染色体17q12微缺失综合征患儿临床资料，应用二代测序技术对全基因组染色体拷贝数变异进行检测，并进行相关文献复习。结果 3例患儿中男2例，女1例。染色体17q12均发现大片缺失（分别为1.89 Mb,1.4 Mb,1.8 Mb），缺失均为新发变异；3例均有肾脏囊肿、高尿酸血症和高碱性磷酸酶；2例有单侧肾脏发育不良及蛋白尿；低镁血症2例，高胆固醇血症2例，肝酶升高1例，糖尿病2例。结论 染色体17q12微缺失综合征是一种影响多器官系统的罕见遗传性疾病，主要表现为肾脏囊肿和发育不良，也可出现糖尿病、高尿酸血症和高胆固醇血症等代谢内分泌异常。     

2q31.1 微缺失综合征1 例报告并文献复习

目的提高对2q31.1微缺失综合征基因型及表型的认识。方法总结分析1例2q31.1微缺失综合征患儿的临床资料并复习相关文献。结果女性患儿,11月龄,自幼全面发育落后伴惊厥2次,特殊面容,肢端畸形,四肢肌张力减低,指、趾畸形;头颅MRI示胼胝体发育不良。应用染色体芯片检测技术,采用比较基因组杂交技术(array-CGH)证实2q31.1-2q31.3区域存在7.279 Mb微缺失:arr 2q31.1q31.3(174570453-181849708)×1。患儿确诊为2q31.1微缺失综合征。文献报道2q31.1微缺失综合征中HOXD基因簇及其调控序列的单倍体剂量不足导致肢端畸形;LNPK功能缺失性变异导致惊厥发作合并胼胝体发育不良的神经发育性疾病,表现为精神运动发育迟滞、智力障碍、肌张力减低、惊厥发作和胼胝体发育不全。该患儿神经系统受累表现与LNPK单基因变异的表型相似,推测患儿神经系统受累可能由LNPK单倍体剂量不足导致。结论对全面发育落后合并肢端畸形者需警惕2q31.1微缺失综合征。     

22q11缺失综合征的研究进展

22q11缺失综合征(22q11DS)是最常见的染色体微缺失疾病.它的临床表现复杂多样,可表现为心脏、颅面、四肢、免疫和内分泌等多系统的异常.其患病率约为1/2500～1/4000.22q11缺失的发病机制是缺失区域内的低拷贝重复序列之间的不对称重组,TBX1基因等被认为是其相关致病基因.     

22q11.2΢ȱʧ�ۺ���7������ٴ����ͼ��������

目的 探讨22q11.2微缺失综合征患儿的不同临床表现.方法 收集2006年7月至2007年6月在英国Oxford儿童医院临床所见的7例经分子细胞遗传学分析(FISH检测)确诊为22q11.2微缺失综合征患儿的临床资料,分析其临床表现、诊断及治疗情况.结果 7例中男2例,女5例.7例均通过FISH检测确诊,1例为产前诊断,余6例的平均确诊年龄为2个月.2例(28.4%)为父母遗传致病,5例(71.6%)为基因突变致病.其中,先天性心脏病和面容异常的发生率均为100%,免疫功能异常28.6%,颚裂14.3%,低钙14.3%.根据患儿的不同临床表现进行对症治疗.结论 22q11.2微缺失综合征患儿以心脏畸形及面容异常为突出表现,结合FISH检测可早期诊断,基因突变是其主要病因,以流出道受损为主的心脏畸形及以T淋巴细胞数量减少为主的免疫功能异常是影响预后的关键因素.     

染色体15q11.2和15q13.3区域的微缺失与中国儿童失神癫的相关性

目的探讨15q11.2和15q13.3区域的拷贝数变异(CNV)是否与中国汉族儿童失神癫(CAE)患儿的表型相关。方法采用Affymetrix SNP 5.0芯片技术对198例CAE患儿和198名北方汉族健康成人进行特发性全面性癫(IGEs)相关的CNV检测,对发现的阳性CNV采用高密度寡核苷酸为基础的比较基因组杂交芯片技术进一步验证。应用Accucopy技术对另外200例CAE患儿进行15q11.2和15q13.3区域的CNV检测。结果通过Affymetrix SNP 5.0芯片技术在198例CAE患儿中发现3例存在15q11.2的微缺失,1例存在15q13.3的微缺失,而在198名健康对照中没有发现。另外200例CAE患儿中发现1例存在15q11.2的微缺失。发现的5例微缺失中除1例为新发CNV外,余4例均遗传自母亲,这些患儿的母亲没有发现明确的癫表现。结论15q11.2和15q13.3的微缺失是CAE患儿重要的疾病相关CNV,并且15q11.2微缺失在中国汉族人群中具有较15q13.3微缺失更高的发生率。     

22q11缺失综合征的研究进展

22q11缺失综合征(22q11DS)是最常见的染色体微缺失疾病.它的临床表现复杂多样,可表现为心脏、颅面、四肢、免疫和内分泌等多系统的异常.其患病率约为1/2500～1/4000.22q11缺失的发病机制是缺失区域内的低拷贝重复序列之间的不对称重组,TBX1基因等被认为是其相关致病基因.     

22q11缺失综合征的研究进展

22q11缺失综合征(22q11DS)是最常见的染色体微缺失疾病.它的临床表现复杂多样,可表现为心脏、颅面、四肢、免疫和内分泌等多系统的异常.其患病率约为1/2500～1/4000.22q11缺失的发病机制是缺失区域内的低拷贝重复序列之间的不对称重组,TBX1基因等被认为是其相关致病基因.     

8q22.2q22.3缺失综合征一例

1例8岁11月龄男性患儿,智力低下,语言落后,1岁9月龄癫痫首次发作,4岁诊断为儿童孤独症,体格检查有特殊面容,视频脑电图示广泛性棘慢波发放。染色体微阵列检测到8q22.2q22.3区域约2.34 Mb片段微缺失,8q22.2q22.3微缺失的病例非常罕见。     

多重连接依赖的探针扩增技术检测先天性心脏病患儿的22q11微缺失

目的 检测先天性心脏病患儿的22q11微缺失情况.方法 采用商品化的多重连接依赖探针扩增(Multiplex ligation dependent probe amplification,MLPA)P250试剂盒,检测100例散发的先天性心脏畸形样本,其中40例产前超声诊断为心脏畸形的胎儿,60例为先天性心脏病患儿.结果 心脏畸形的胎儿有2例为22q11微缺失,先天性心脏病患儿有1例22q11微缺失;3例检测出22q11微缺失的患儿,2例为3M典型缺失,1例为非典型缺失.结论 在先天性心脏病患儿中存在22q11微缺失.

Abstract：

Objective To detect 22q11 microdeletion in the children and fetuses affected by congenital heart defects.Method MLPA P250 kit was used to detect 22q1 1 microdeletion in 100 cases of sporadic congenital heart defects including 40 fetuses and 60 patients diagnosed by ultrasound.Result Two cases from the fetuses and 4 case from the patients were found to have 22q11 microdeletion.Conclusion Three cases had 22q11 microdeletion in the congenital heart defects.     

先天性食管旁疝20例报告

为了回顾和评价先天性食管旁疝各种术式的治疗效果，总结近十余年中经手术治疗的食管旁疝２例。患儿男１５例，女５例，年龄３天～６．５岁。本组半数误诊为肺脓肿或其他疾病。治疗结果：２例行Ｂｅｌｓｅｙ术，均复发；１５例行Ｎｉｓｓｅｎ术，术后１例折叠过紧，１例并发回肠套叠，３例食管下段轻度狭窄，余１１例随访２～１０年，２例有折叠部分疝出；Ｔｈａｌ手术２例，近期效果好。由于该病易发生胃扭转或嵌顿，确诊后应立即手术。应注意防治Ｎｉｓｓｅｎ手术后发生折叠过紧及滑脱等并发症，Ｔｈａｌ术的近期疗效好。     

Endocrinological Abnormalities in Prader-Willi Syndrome

Ten patients with typical Prader-Willi syndrome were studied for their short stature, hypogonadism, and obesity. Tne following results were obtained.

• 1) GH secretion was variable, ranging from subnormal to normal, although all shared short stature in common.
• 2) Two of the 4 adolescent patients were diagnosed as having hypo-gonadotropic hypogonadism. The remainder disclosed normal response to LH-RH stimulation. Of the two patients with normal LH-RH stimulation test, one showed normal testosterone production.
• 3) In one child who developed overt diabetes, there remained elevated basal plasma insulin and depressed RBC-insulin binding, despite weight control. There appears to be a significant heterogeneity in endo crinological derangement of Prader-Willi syndrome.

     

MICROBIAL FLORA AND DISACCHARIDASE DEPRESSION IN INFANTILE GASTROENTERITIS

Abstract. Barnes, G. L., Bishop, R. F. and Townley, R. R. W. (Department of Gastroenterology, Royal Children's Hospital, Melbourne and Department of Paediatrics, University of Melbourne, Victoria, Australia). Microbial Flora and Disacharidase Depression in Infantile Gastroenteritis. Acta Paediatr Scand, 63: 423, 1974.–In infants with acute gastroenteritis, disaccharidase activity in duodenum is depressed in a majority of patients. There is a statistically significant association between abundant growth of Candida albicans in the duodenum and depression of lactase activity at the same level.     

Mineral homeostasis in very premature infants: serial evaluation of serum 25-hydroxyvitamin D, serum minerals, and bone mineralization

This study was designed to evaluate the role of vitamin D sufficiency, as reflected in serum 25-hydroxyvitamin D (25-OHD) concentrations, on serum minerals and bone mineralization in very premature infants. Seventy-two infants (mean +/- SD gestation 30.1 +/- 2.5 weeks, mean +/- SD birth weight 1178 +/- 278 gm) were observed serially for the first 3 months of life. Mean serum calcium and phosphorus values, but not magnesium, remained low prior to 12 weeks. The percentage of infants with moderate to severe hypomineralization was 75% at 3 weeks, 55% at 6 weeks, 54% at 9 weeks, and 15% at twelve weeks. Low serum calcium and phosphorus values, high alkaline phosphatase activity, and moderate-severe hypomineralization were more frequent in infants weighing less than 1000 gm and in those with lower mineral intake. With a 400 IU vitamin D supplement, 45% of infants could maintain an initially normal serum 25-OHD concentration or increase low concentrations, whereas 55% had falling or persistently low (less than or equal to 15 ng/ml) 25-OHD concentrations. Birth weight and mineral intakes were comparable in these two groups, yet the group with the lower serum 25-OHD concentration had lower serum calcium and higher alkaline phosphatase values, and a higher percentage of moderate to severe hypomineralization. Regardless of birth weight, mineral intake, or 25-OHD concentration, increases in serum calcium and phosphorus values and in mineralization were seen at postconception term (12 weeks in most infants, nine weeks in those weighing 1250 to 1600 gm). At 12 weeks of age, but not before, serum 25-OHD concentration was directly correlated with serum calcium (r = 0.47, P less than 0.01) and serum phosphorus (r = 0.47, P less than 0.01) and inversely correlated with alkaline phosphatase values (r = -0.71, P less than 0.01). Mineral availability and 25-OHD sufficiency both appear to be important and to act synergistically, with neither totally compensating for the other.