45，X/46，XY嵌合体性腺表型与分子生物学分析

目的:探讨45,X/46,XY嵌合体患儿性腺特征、性腺肿瘤的发生率及 SRY基因及Y染色体微缺失检测结果。 方法:回顾性分析2013年1月至2019年12月在江西省儿童医院就诊的45,X/46,XY核型或其变异型患儿的病例资料,对45,X/46,XY嵌合体性腺表型及分子生物学进行分析。结果:30例...     

92例先天性智力低下患儿细胞遗传学分析

目的：探讨先天性智力低下患儿染色体核型变化。方法：取92例先天性智力低下患儿外周血混合淋巴细胞培养,制备染色体,利用G显带技术对其进行染色体核型分析。结果：92例患儿中,检出异常染色体核型43例,检出率47%。其中,常染色体异常35例,占38%;性染色体异常8例,占9%;新发现1例智力低下异常核型:45,XX,psu dic（11;9）（p15;p24）。结论：染色体异常是导致先天性智力低下的重要原因,外周血细胞遗传学分析有助于提高先天性智力低下病人的遗传学筛查率。     

新发9号染色体异常患儿的临床和细胞遗传学研究

分析9号染色体短臂缺失或重复患儿的临床表型及其与染色体核型的关系。患者,女,6个月,因运动发育迟缓就诊,染色体核型分析确定为9号染色体短臂异常,高通量测序分析发现存在9p24.3-9p23区域缺失和9p23-9p13.1区域重复,其父母染色体核型分析正常。核型分析结合高通量测序对于提高运动发育落后或多发先天畸形和智力落后患者的病因诊断效率具有重要意义。     

2064例细胞遗传学分析临床与优生意义

为了解国内主要异常染色体核型的分布情况，给优生干预提供科学的依据，对2064例患者进行常规接种、培养并制备外周血淋巴细胞染色体G显带标本，必要时进行C带和高分辨G显带分析。结果显示，2064例患者中，染色体异常457例，异常检出率为22．1％，涉及异常核型80余种。染色体异常中常染色体异常263例，性染色体异常194例；染色体数目异常315例，结构异常116例，性反转26例。提示染色体核型分析是诊断染色体病、检出携带者以及进行产前诊断的主要方法；21-三体综合征和Turner综合征是临床最常见的染色体异常，其染色体核型复杂多样。     

1750例遗传咨询儿童细胞遗传学研究

目的探讨遗传咨询儿童染色体核型情况,研究染色体异常与疾病的关系。方法对1 750名遗传咨询儿童进行外周血染色体核型分析。用多重连接探针扩增技术(MLPA)检测染色体的亚端粒,确定小标记染色体(SMCs)的来源。结果共检出异常核型242例,异常率13.8%。常染色体数目异常181例,占异常核型的74.8%;常染色体结构异常28例,占11.6%;性染色体异常22例,占9.1%;染色体多态性11例,占4.5%。发现1例45,XX,psu dic(11;9)(p15;p24)核型,该核型为世界首次报道。结论染色体异常是导致儿童生长发育迟缓、智力低下和性分化异常等疾病的重要原因之一,常规染色体检查,可为临床诊断和治疗提供科学依据。     

5 例低磷酸酯酶症患儿临床及遗传学分析

目的总结低磷酸酯酶症(HPP)的临床及遗传学特点。方法回顾分析5 例HPP患儿的临床资料,以及患儿及其亲属的外周血高通量测序及Sanger验证结果。结果 5例患儿均有骨骼矿化不良以及血清碱性磷酸酶降低,3例伴有惊厥等神经系统症状。5例HPP患儿高通量测序共发现ALPL6个突变位点,c.346GA(p.A116T)、c.1097至c.1099del CCT复合杂合突变(p.T366_S367deli)、c.1014至c.1015ins G(p.H338fs)、c.1446CA(p.482HQ)复合杂合突变、c.920CT(p.P307L)、c.883AG(p.M295V),其中c.1014_c.1015ins G、c.1097_c.1099del CCT、c.1446CA为首次报道,蛋白质结构预测均为可能有害,ACMG评级为可能致病。结论确诊5例HPP患儿,发现 3种新型突变,丰富了人类ALPL基因突变数据库。     

一例13号环状染色体综合征患儿的临床及遗传学分析

患儿,女,5个月,因生长发育迟缓就诊,体格检查发现体格发育落后,特殊面容（小头畸形、眼距宽、耳位偏低、鼻梁扁平、短人中）以及一侧小阴唇缺失。外周血染色体核型为46,XX,r（13）（p11q33）[82]/45,XX,-13[10]/46,XX,r（13;13）（p11q33;p11q33）[8];微阵列比较基因组杂交（aCGH）检测显示13q11q33.2区域和13q33.2q34区域分别有87.5 Mb的重复和8.2 Mb的缺失;荧光原位杂交（FISH）显示13号环状染色体长臂末端缺失。诊断为13号环状染色体综合征。该综合征临床表型多变,主要与染色体区带中遗传物质丢失的数量、部位以及不同核型嵌合比例不同等密切相关。     

12p三体新生儿1例临床及细胞分子遗传学分析

目的探讨12p三体新生儿的临床及细胞分子遗传学特点。方法回顾1例经外周血行淋巴细胞常规G显带染色体核型分析,高通量测序染色体组拷贝数分析(CNV)并经淋巴细胞间期荧光原位杂交(FISH)技术确认的12p三体新生儿的临床资料。结果患儿外周血染色体核型为47,XX,+mar,父母染色体核型均正常;CNV检出患儿12p13.33-p11.1(160 001～34 860 000)区域重复,片段大小为34.7 Mb;外周血淋巴细胞间期FISH显示患儿所有间期细胞核12号染色体短臂均存在3个信号,无嵌合体存在。确诊为12p三体。结论结合临床特征、外周血染色体核型分析、CNV及FISH技术可有效确诊12p三体。     

186例矮小症患者遗传学检测结果分析

目的 探讨儿童矮小症的遗传学病因。方法 选取2017年1月—2020年10月因生长缓慢就诊的矮小症患儿为研究对象。行矮小相关基因的全外显子测序,对发现的可能的染色体片段拷贝数变异者进一步完善基因芯片检查,比较基因检测阳性与阴性组之间临床表型差异。结果 共纳入186例矮小症患儿,中位年龄7.3(5.1～9.1)岁,男103例、女83例。共检测出69例阳性结果,阳性检出率37.1%。其中54例通过全外显子基因测序诊断,15例通过染色体微阵列分析诊断。二元logistic回归分析显示,特殊面容和骨骼发育异常是儿童矮小症基因检测结果阳性发生的预测因素(P均<0.05)。结论 全外显子测序是检测儿童矮小症遗传病因的有效技术手段,伴有特殊面容和/或骨骼发育异常的患儿更可能检测到遗传病因。     

21三体综合征46例染色体核型分析

目的分析21三体综合征（DS）患儿的染色体核型，为降低DS的风险提供产前诊断依据。方法对智力低下206例儿童进行详细的遗传咨询：遗传病史（有遗传病史进行系谱分析）、DS临床体征、父母的染色体及生育年龄情况、父母接触有害物质情况。行外周血淋巴细胞培养，行常规G显带核型分析。对气促、发绀、心脏杂音、心电图和胸片等可疑有先天性心脏病者，应用彩色多普勒超声心动图（CDFM）检查；DS 1例患儿有脑性瘫痪症状，行脑电图、头颅CT检查；经确诊为DS的患者，患者父母做染色体核型分析。结果确诊DS患者46例，其中21三体型42例（占92％）；易位型21三体2例（占4％）；嵌合型21三体2例（占4％）。DS并先天性心脏病16例（占35％）；并脑性瘫痪1例（占2％）。DS患儿46例父母的染色体核型均正常。结论开展细胞遗传学诊断分析，可精确检出DS，对DS高危人群未来的生育后代情况及预防DS患儿的出生提供科学依据。     

Presence of Turner stigmata in a case of dysgenetic male pseudohermaphroditism with 45,X/46,X+mar karyotype

A case is reported of dysgenetic male pseudohermaphroditism (DMPH) having Turner stigmata and 45,X/46,X+mar karyotype. The marker chromosome of this patient consisted of most if not all of the short arm, including the sex determining region of the Y chromosome. Although this karyotype is relatively common in Turner's syndrome and occasionally observed in mixed gonadal dysgenesis, DMPH is usually exemplified by a 46,XY karyotype except for one patient reported with 45,X/46,XY mosaicism. Turner stigmata have not previously been reported in DMPH. The present patient is an intermediate case between mixed gonodal dysgenesis and typical DMPH, and this indicates that 45,X/ 46,X +mar karyotype abnormality can result in a wide range of phenotype such as DMPH, mixed gonodal dysgenesis and Turner's syndrome.     

Short stature in children with an apparently normal male phenotype can be caused by 45,X/46,XY mosaicism and is susceptible to growth hormone treatment

Girls with unexplained short stature are routinely screened for the presence of Ullrich-Turner syndrome by clinical examination, laboratory tests, and karyotyping. In this study, we performed chromosomal analysis in boys to explore the role of 45,X/46,XY mosaicism for short stature in males. Short-term effects of growth hormone treatment in male 45,X/46,XY individuals were compared retrospectively to those in female patients. We report six boys with a normal-appearing male phenotype and 45,X/46,XY mosaicism, four of whom were diagnosed postnatally because of short stature. Two boys were diagnosed prenatally by amniocentesis. Five boys were short and were treated with growth hormone (0.04–0.05 mg/kg per day) in analogy to girls with Ullrich-Turner syndrome and gonadal dysgenesis. With the exception of one patient in whom treatment was initiated only at the age of 14.6 years, the male patients with 45,X/46,XY mosaicism responded to short-term growth hormone treatment similarly to females with an increasing height SDS. Conclusion:45,X/46,XY mosaicism remains undetected in some short boys because this group is not routinely karyotyped. We recommend chromosomal analysis of boys with otherwise unexplained short stature who are short for their families. Growth hormone treatment should be offered to short boys with 45,X/46,XY mosaicism and a predicted adult height below the mid-parental range within clinical trials.Abbreviations FSH follicle stimulation hormone - GH growth hormone - IGF-I insulin-like growth factor 1 - IGFBP-3 insulin-like growth factor binding protein-3 - LH luteinising hormone - MPH mid-parental height     

Description of children with 45,X/46,XY karyotype

We hypothesized that because 45,X/46,XY (X/XY) children share a cell line with Turner syndrome (TS), they also share co-morbidities described in TS. In addition, the presence of the Y chromosome in brain and in other body tissues would influence their function. On the basis of our findings, we aimed to establish optimal procedures for clinical evaluation, management, and follow-up of these children. Sixteen X/XY children were evaluated and managed at a single institution as part of standard clinical care as established at the time between 1969 and 2009. In January of 2005, we started retrospective record review of all X/XY children in combination with cohort follow-up (of those who had not reached adult height) until August of 2009. The study included review of clinical presentation, clinical characteristics, diagnostic measures, radiologic studies, karyotype studies, psycho-endocrinology evaluation, and growth-promoting treatments. There was no specific intervention. Phenotype reflected cell line distribution. The presence of 45,X cell line explains how X/XY children have abnormalities similar to girls with TS, while presence of Y chromosome explains why they have tomboyish behavior. In conclusion, these children require clinical evaluation similar to that performed in female children with TS, including cardiovascular, renal, endocrine, growth and development, autoimmune, psychological, and educational evaluation. Specific management needs to be tailored to the presence of Y chromosomal material.     

45,X/46,XY嵌合型伴性发育障碍五例分析

Objective To analyze clinical characteristics of children with 45,X/46,XY mosaicism and explore effective managements for them.Method Five children with 45,X/46,XY mosaicism were all in puberty period,of whom,three were female and two male.The standing height,weight and sexual development were measured.The levels of sex hormones,other endocrine parameters were also determined,and imaging examinations were performed.Result All the patients had disorders of sex development,of whom.4 had short stature,and the HtSDs was -2.8±1.1.The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism,with the average level of LH(1 3.5±5.8)IU/L and FSH(56.8±37.4)IU/L.Imaging examinations revealed that 2 cases had eryptorchidism,1 had immature uterus,1 had testicular dysgenesis and 1 had normal testis.Three patients received rhGH treatment and 1 took gender assignment into account.Conclusion Patients with mosaic 45,X/46,XY karyotypes had a wide range of phenotypic manifestations.and disorders of sex development and short stature were the main clinical features.However,the disorders of sex development varied among these patients.And the managenlent for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.     

45,X/46,XY mosaicism

The clinical findings in ten patients with 45,X/46,XY mosaicism are described. Three girls presented with short stature, delayed sexual development or Turner-like stigmata without signs of virilization. Bilaterally gonadoblastomas were found in two girls, and the gonads in one of these girls also contained mucinous cystadenomas. The remaining seven patients were raised as boys. Three had scrotal hypospadias and mixed gonadal dysgenesis. Three presented as male pseudohermaphrodites with scrotal or penoscrotal hypospadias and bilateral testes. One male was diagnosed in adulthood because of gynecomastia, but had normal male external genitals. The clinical findings illustrate the wide spectrum of phenotypic manifestations of 45,X/46,XY mosaicism, ranging from females with Turner-like phenotypes, phenotypic males and females with mixed gonadal dysgenesis, male pseudohermaphroditism to almost phenotypic normal males.     

45,X/46,XY嵌合型伴性发育障碍五例分析

目的 分析5例45,X/46,XY嵌合型患儿临床特征,探讨合理有效的治疗方案.方法 本院5例45,X/46,XY嵌合型患儿,3例社会性别为女性,2例为男性,均处于青春发育年龄.测量身高、体重、第二性征及性腺发育状况;检测性激素水平及其他内分泌学相关指标,行性腺影像及盆腔探查.结果 5例45,X/46,XY嵌合型患儿均表现为性发育障碍.其中4例有不同程度的身材矮小,身高标准差积分为-2.8±1.1;实验室检查提示4例患儿为高促性腺激素性腺功能减退,黄体生成素(基)为(13.5±5.8)IU/L,卵泡刺激素(基)为(56.8 ±37.4)IU/L;性腺影像学检查示2例隐睾,1例幼稚子宫,1例睾丸形态较小,睾丸组织活检示发育不良,1例睾丸发育尚可.3例试行重组人生长激素治疗,1例现考虑进行性别转换.结论 45,X/46,XY嵌合型患儿临床表现为性发育障碍和(或)身材矮小,但性发育障碍可表现多样.应针对患儿自身特点,多科间协作制定个体化的治疗方案.

Abstract：

Objective To analyze clinical characteristics of children with 45,X/46,XY mosaicism and explore effective managements for them.Method Five children with 45,X/46,XY mosaicism were all in puberty period,of whom,three were female and two male.The standing height,weight and sexual development were measured.The levels of sex hormones,other endocrine parameters were also determined,and imaging examinations were performed.Result All the patients had disorders of sex development,of whom.4 had short stature,and the HtSDs was -2.8±1.1.The results of laboratory indexes suggested that 4 had hypergonadotropic hypogonadism,with the average level of LH(1 3.5±5.8)IU/L and FSH(56.8±37.4)IU/L.Imaging examinations revealed that 2 cases had eryptorchidism,1 had immature uterus,1 had testicular dysgenesis and 1 had normal testis.Three patients received rhGH treatment and 1 took gender assignment into account.Conclusion Patients with mosaic 45,X/46,XY karyotypes had a wide range of phenotypic manifestations.and disorders of sex development and short stature were the main clinical features.However,the disorders of sex development varied among these patients.And the managenlent for them depends upon many factors and needs to be individualized based on the cooperation with different clinical departments.     

45,X/46,X dic (Y) mosaicism in a phenotypic male.

Cytogenetic analysis, confirmed by in situ hybridisation studies, showed a mosaic 45,X/46,X dic (Y) (q12) karyotype in a 14 year old boy who was initially diagnosed as having Noonan''s syndrome. He made an early response to recombinant growth hormone; this suggests that this treatment may improve final height.     

45,X/47,XY,+ 13 Mosaicism and Crohn's Disease

ABSTRACT. The unusual karyotype 4S,X/47,XY,+13 in an 8.5-year-old girl with the Turner phenotype is described. She displayed none of the phenotypic manifestations of trisomy 13. The patient suffered from Crohn's disease, which is known to be associated with the Turner syndrome. To our knowledge this is the first reported case of Crohn's disease in a patient with 45,X and Y chromosome mosaicism.     

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目的调查肥胖及矮小儿童自我意识水平,探讨其与正常儿童自我意识方面的差异。方法 2008年8月至2008年12月用Piers-Harris儿童自我意识量表对湖南省长沙市7所中学中86例肥胖及69例矮小儿童进行心理健康调查。结果肥胖儿童在行为、躯体外貌、合群、焦虑及自我意识总分得分均低于全国常模水平,差异有统计学意义(P<0.05或0.01);肥胖儿童在智力与学校及幸福与满足两个分量表得分与全国常模水平的差异无统计学意义(P均>0.05)。矮小儿童在行为、躯体外貌、幸福与满足、合群及自我意识总分得分均低于全国常模水平,差异有统计学意义(P<0.05或0.01);矮小儿童在智力与学校表现及焦虑两个分量表得分与全国常模水平差异无统计学意义(P均>0.05)。结论肥胖及矮小儿童自我意识水平较正常同龄儿童低,且其自我意识水平高低程度不一。青少年的自我意识水平与躯体疾病密切相关,有必要在医学治疗的基础上加入相应的心理干预措施以促进其身心健康。