猫叫综合征一例及临床分析

病例：患儿,男,37天;因“生后哭声弱一月余”入院;患儿系G2P2,孕42周,自然分娩,无窒息抢救等异常生产史,出生时体重2．340kg,生后家属便发现患儿哭声弱、类似猫叫、吃奶差、易疲劳,大小便尚正常,便一直未予重视。查体：神清,精神反应差,营养发育差,哭声弱、似猫叫,体重3．060kg,身长46cm,小头,头围33cm,圆脸欠对称,双眼距明显增宽,鼻梁扁平,睑裂下斜,眉心圆形隆起,小下颌,通贯手,阴茎短小,双侧睾丸已降,呼吸促,     

5p缺失综合征并先天性心脏病临床和细胞遗传学一例报告

5p-综合征是由5号染色体短臂缺失(或部分缺失)引起的一种少见的染色体病。本文报告1例出生6个月的女婴,哭声如猫叫,反应较迟钝,双眼距宽,尖下颌,右耳前有赘生物,肌张力轻度低下,伴有先天性心脏病。外周血染色体核型为46,XX,r(5)/46,XX嵌合体,经文献检索未见报道。     

一例不典型新生儿猫叫综合征的遗传学分析CSCD

目的对1例仅表现为哭声无力,声音嘶哑,无特殊面容,不伴有先天性心脏病等其他症状或体征的不典型新生儿猫叫综合征患儿的临床及遗传学特点进行分析。方法对患儿及其父母外周血淋巴细胞G显带染色体核型分析,对患儿用应荧光原位杂交技术（fluorescence in situ hybridization, FISH）进行验证,之后用染色体微阵列法（chromosome microarray analysis, CMA）进一步精确遗传学分析。结果患儿染色体核型分析结果为46,XX,del（5）（p14p15）,其父母外周血染色体核型分析未见异常。FISH结果证实了此缺失的存在。染色体微阵列检测结果显示患儿chr5p15．33p14．1区域存在25．7Mb片段缺失。结论猫叫综合征患者个体表型可存在较大差异,尤其是对于新生儿易导致漏诊、误诊。应用细胞遗传学与分子遗传学技术相结合的综合分析有利于弥补单一方法的不足,更加精确地对缺失片段进行定位。     

猫叫综合征的细胞遗传学和临床分析

猫叫综合征是由于5号染色体短臂部分缺失所引起的一种染色体病,因在婴儿期和幼儿期哭声如猫叫而得名,又称为5p-综合征。2008年12月到2009年4月,我院遗传室发现两例5p-综合征患儿,现报告如下。     

3例猫叫综合征细胞遗传学分析及文献回顾

猫叫综合征又称５ｐ－综合征，因在婴儿期和幼儿期哭声如猫叫而得名。群体发病率为１／４５０００，女性占７０％。此病严重智力低下和生长发育障碍，具小头、圆脸、小下颌等特殊面容，外周血染色体培养常规即可检出。本室检出了３例５ｐ－患儿，２女１男。染色体核型证实，有２例患儿为５ｐ１３缺失，１例患儿为５ｐ１５缺失，但都具有特定的面容，说明５号染色体短臂上微小的缺失，均会造成此综合征遗传表型。     

父源性平衡易位致子代猫叫综合征1例

目的 追踪分析发现1例猫叫综合征（CDCS）的患者,为临床医生把握产前诊断指针及选择多种检测技术联合诊断提供参考。方法 对1例高龄、胎儿超声软指标异常的孕妇进行产前诊断,孕妇本人及其丈夫和儿子行外周血染色体核型分析,其儿子行CNVs以明确病因。结果 胎儿染色体核型结果为46,X?,t(5:17)(p15.2;q25.3),CNVs结果未见明显异常。先证者CNVs结果显示chr5p15.33p15.2区域存在13.64Mb的杂合缺失,其外周血染色体结果为46,XY,del(5)(p15.2),提示为猫叫综合征。先证者父亲的外周血染色体结果为46,XY,t(5:17)(p15.2;q25.3),其母亲未见明显异常。结论 临床医生应详细询问病史,严格把握产前诊断指针,应用细胞遗传学与分子遗传学相结合的技术综合分析,实现对猫叫综合征的早发现、早干预。     

一对夫妇连续生育两胎猫叫综合征患者的遗传分析

我们在遗传咨询中发现一对夫妻连续生育两胎猫叫综合征患者,并对其进行家系调查和染色体核型分析.现报告如下.     

猫叫综合征3例

临床病例例 1:男 ,14天 ,因气促、口吐白沫 12天入院。患儿第 1胎 ,孕 42周经用催产素娩出 ;出生时呈轻度窒息 ,第 3天出现气促、口吐白沫。母孕期健康。体检 :体重 3.5ｋｇ ,身长5 0ｃｍ ,头围 33ｃｍ ,呼吸 68次 /分 ,反应差 ,双肺细胞罗音 ,心脏无异常 ,肝肋下 2ｃｍ ,脾未及 ,双手呈通贯掌 ,第 3、4、5指关节屈曲不能伸直。住院期间发现患儿哭声似猫叫。染色体检查 ,核型 :46,ＸＹ ,ｄｅｌ(5 ) (ｑｔｅｒ→ｐ13)。其父母染色体未发现异常。例 2 :女 ,9个月。因发热、咳嗽、气促入院。患儿第 1孕第 1胎 ,孕 2 4周时母患感冒 ,孕 2 8周发…     

猫叫综合征关键区域定位于5p15.2的D5S713—D5S18区域

猫叫综合征是由５号染色体短臂缺失引起的染色体缺失综合征。根据染色体综合征“关键区域”的概念，以及近１０年来对１０６例５ｐ缺失病例的临床诊断、细胞遗传学及分子遗传学分析，将猫叫综合征的关键区域定位于５ｐ１５．２，位于Ｄ５Ｓ７１３和Ｄ５Ｓ１８两个遗传标记之间的区域。为研究该病提供了遗传学资料。     

南昌地区18例猫叫综合征染色体核型和临床分析

目的探讨猫叫综合征的染色体关键区域与临床特征的关系。方法采用外周血淋巴细胞染色体培养,G显带及核型分析。结果从1988年至今通过染色体检查,共发现18例猫叫综合征,男性9例,女性9例,其中del（5）（p12）2例,del（5）（p13）8例,del（5）（p14）5例,del（5）（p15）3例。结论猫叫综合征的关键区域是5p15.2,主要特征为婴儿期因喉软骨、咽喉肌发育不良而哭声似猫叫和特殊面容,严重智力低下及其他畸形。通过染色体检查,遗传咨询,对优生优育具有重要意义。     

Ring chromosome 5 in two malformed boys with Cri du Chat syndrome

Two cases of Cri du Chat syndrome were found to have a ring chromosome 5 in almost all their cells. The lack of the No. 5 short arm p15 band in both cases sufficed to produce the well-known features.     

Cri du chat syndrome determined by the 5p15.3-->pter deletion--diagnostic problems

A cytogenetic analysis was performed on an 8-day-old girl, who was suspected of Cri du chat syndrome (CdCS) on the basis of a cat-like cry, despite her dysmorphic features not being characteristic of this syndrome. The cytogenetic analysis revealed a partial deletion of the short arm of chromosome 5, but did not allow precise specification of the break points. Fluorescence in situ hybridization (FISH) analysis, using the specific probe for CdCS, revealed two signals in all the cells analyzed. However, one of two signals was less intense than the other. Thus, telomere probes were applied for all chromosomes. Two signals from 5q and one signal from 5p were observed. The results allowed us to establish the location of the deleted fragment as 5p15.3-->5pter [46,XX,del(5)(p15.3)]. The analysis of a genotype-phenotype correlation confirmed that the cat-like cry, but not the characteristic dysmorphic features of CdCS are correlated with the deletion of 5p15.3.     

微阵列比较基因组杂交技术分析一例猫叫综合征患儿的基因组拷贝数变异

目的 对1例猫叫综合征患儿进行基因组拷贝数分析,寻找其致病原因.方法 对患儿外周血进行常规G显带分析,应用微阵列比较基因组杂交技术进行全基因组扫描,并应用荧光原位杂交技术对异常拷贝数区域进行验证.结果 患儿染色体核型为46,XY,der(5)(p?).微阵列比较基因组杂交显示其在5p14.2-p15.3处存在23.263Mb的片段缺失,12号染色体12p31区域存在14.602 Mb的片段重复.重复片段连接至5p14.2处,形成5号衍生染色体,即arr cgh 5p15.3p14.2(PLEKHG4B→CDH12)×1 pat,12p13.33p13.1(IQSEC3→GUC Y2C)× 3 pat.荧光原位杂交证实患儿存在5p末端缺失及12p末端重复.结论 5号染色体不平衡易位导致患儿5p末端缺失可能是患儿的病因.微阵列比较基因组杂交技术具有高分辨、高通量和高准确性的优点,适用于全基因组拷贝变异分析.     

应用多重连接依赖探针扩增技术分析自然流产绒毛染色体异常的研究

目的 探讨多重连接依赖探针扩增(multiplex ligation dependent probe amptification,MLPA)技术在孕早期自然流产绒毛组织染色体分析中的应用.方法 195例自然流产患者留取绒毛组织,包括12例已污染标本,其余183例标本进行绒毛细胞培养及染色体G显带核型分析,同时应用P036和P070试剂盒对195例标本作MLPA分析.结果 183例标本成功培养177例,其中160例(90.4％)采用MLPA技术进行染色体分析的非整倍体结果与G显带染色体核型分析方法的结果一致,包括正常核型65例、所有染色体三体78例、所有染色体单体14例(除1例嵌合体)和不平衡易位3例;G显带核型分析结果异常的15例标本中包括10例多倍体及2例平衡易位,2例9号倒位及1例嵌合体异常MLPA结果显示正常;此外MLPA检测出1例Dup6p;dup6q和1例Dup8p;del 11q,G显带分析结果显示为46,xx和46,xy.结论 MLPA技术对非整倍体异常的检出与经典的染色体核型分析是一致的,同时它能快速的检测出染色体非平衡结构异常以及经典染色体核型分析不能检测的微缺失和微重复,是一种简单、快速且有效的方法,具有临床实际应用价值.     

Use of multiplex ligation-dependent probe amplification increases the detection rate for 11p15 epigenetic alterations in Silver-Russell syndrome

Silver–Russell syndrome (SRS) describes a malformation syndrome with severe intrauterine and postnatal growth retardation. Currently, two major (epi)mutations have been described: while approximately 10% of patients carry a maternal uniparental disomy of chromosome 7 (UPD7), 35–60% show a hypomethylation at the H19 differentially methylated regions (DMRs) in 11p15. Until recently, a Southern-blot based test was routinely used to identify epimutation carriers. Nevertheless, this test was time consuming and hampered by the huge amount of genomic DNA needed. With the methylation-specific multiplex ligation-dependent probe amplification assay (MLPA) for SRS, a PCR-based test is now available, allowing the analysis also of small amounts of DNA. Probes in this assay hybridize to the H19 DMRs but do not cover the genomic target of the Southern-blot probe. We now screened 72 patients with SRS by MLPA. Hypomethylation of the H19 DMRs was confirmed in all patients analyzed by Southern blot. In addition, we identified six individuals with hypomethylation of the H19 DMR who had previously normal blot results. This discrepancy can be explained by the observed generally lower degree of demethylation in this group, possibly not detectable by the less sensitive Southern-blot method but also with a varying degree of methylation at different DMRs in the same individual. Apart from hypomethylation in the H19 DMR, we observed a slight demethylation for one of the IGF2 probes. The total detection rate of 11p15 hypomethylation is now increased to >38%. Considering maternal UPD7 and chromosomal aberrations, (epi)genetic alterations now account for more than 50% of SRS patients. In summary, MLPA represents an easy, low cost and reliable system in the molecular diagnostics of SRS.     

兰州地区61例Turner综合征核型及临床特征分析

目的探讨Turner综合征患者的染色体核型异常与内分泌激素异常、发育异常和骨龄落后的关系。方法对61例Turner综合征患者进行染色体核型分析、内分泌激素六项检测、B超检查及身高评价。选择同期健康体检人群作为对照组。结果 Turner综合征染色体核型各异,患者表现为身材矮小和躯体畸形,B超检查患者无子宫和/或卵巢,与正常对照组相比发育明显落后（P〈0.01）;患者血清FSH、LH明显高于对照组,E2、P低于对照组,PRL、T无明显差异;身高及骨龄明显落后。结论 Turner综合征的染色体核型与患者临床表现相关,骨龄落后和身材矮小可能与SHOX基因缺乏、雌激素缺乏有关。     

A neuropsychological-genetic profile of atypical cri du chat syndrome: implications for prognosis

Cri du chat syndrome is associated with a deletion on the short arm of chromosome 5. The main diagnostic feature is a high pitched, cat-like cry which has recently been localised to 5p15.3 and is separate from the remaining clinical features of the syndrome, which have been localised to 5p15.2. The present study describes a family of four who have a deletion slightly distal (5p15.3) to the critical region. Detailed neuropsychological evaluations indicated a similar pattern of cognitive performance to that reported for subjects with typical CDCS but with only minimal intellectual impairment. In addition, in this family the 5p deletion is transmitted in an autosomal dominant fashion, contrasting with most cases of CDCS, which are either de novo or occur as an unbalanced product of a balanced translocation in a normal parent. This study confirms the importance of differentiating between 5p deletions that coincide with the typical cri du chat phenotype which includes severe to profound learning disability and deletions that only delete the distal critical region that coincides with a milder degree of cognitive impairment and a much improved prognosis.     

Expansion of CD3+CD4-CD8- T cell population expressing high levels of IL-5 in Omenn's syndrome.

Omenn's syndrome is a fatal, autosomal-recessive combined immune deficiency characterized by several erythematous exfoliative eruptions, lymphadenopathy, hepatosplenomegaly, and elevated eosinophil count. In some of these patients an expansion of CD3+CD4-CD8- double negative (DN) T cell population was observed. We show here that the DN population represents a clonal expansion of T cells which preferentially use V beta 14 in their T cell receptor complex. Using polymerase chain reaction, we show that patient's DN cells express spontaneously high levels of IL-5, thus possibly explaining the abundance of eosinophils in this disorder. The increase of IgE observed in patients with Omenn's syndrome is unlikely to be related to IL-4 production, as IL-4 levels in patient samples were low. However, patient's low expression of interferon-gamma (IFN-gamma), which has been reported to inhibit IgE production, may explain the elevated levels of IgE in this patient. The results thus highlight the importance of the inhibitory effect of IFN-gamma on regulation of IgE production.