13号环状染色体综合征1例报告及文献复习

目的探讨13号环状染色体综合征的进展。方法对1例13号环状染色体综合征患儿的症状、体征和影像学检查进行分析,应用染色体常规G显带和C显带技术进行分析,并通过文献复习对13号环状染色体综合征患儿例进行回顾分析。结果本例患儿智力及语言发育落后、生长迟缓;小头畸形、内眦赘皮、眼距宽、腭弓高尖、颈短、耳位低、左手通贯掌;头颅CT、MRI未见异常,心脏彩超、腹部B超均未见异常;患儿核型为45,XX,-13/46,XX,r(13;13)(13;13q21.2→32);环状染色体中的1条只保留了q21.2→32片断。患儿双亲核型正常。结论本例患儿核型是1种少见的13号环状嵌合体;13号环状染色体综合征临床表型多样,与断裂点之间的关系仍不明确;13号环状染色体长臂缺失可分为4类;新着丝粒在有丝分裂和减数分裂过程中起重要作用。     

新发8p 重复伴缺失综合征患儿细胞分子遗传学研究

目的探讨8号染色体短臂倒位重复伴末端缺失[inv dup del(8p)]综合征的临床特征及细胞分子遗传学特点。方法回顾分析1例inv dup del(8p)综合征患儿的临床资料以及细胞分子遗传学分析资料。结果 6月龄女性患儿,具有发育迟缓、特殊面容、先天性心脏病及喉软化症等临床表现。外周血淋巴细胞染色体核型分析显示,患儿为46,XX,der(8)inv dup(8)(p21),del(8)(p23),父母均无异常;高通量测序染色体组拷贝数分析(CNV)精确定位拷贝数异常改变的染色体片段区域,检出患儿在8p23.3-p23.1(160 001-7 120 000)区域缺失6.96 Mb片段,在8p23.1-p21.1(12 560 001-27 940 000)区域,重复15.38 Mb片段;荧光定量PCR验证CNV显示在重复和缺失片段之间有一个5.4 Mb的拷贝数正常片段。结合临床表现及各检测结果确诊患儿为inv dup del(8p)综合征。结论结合临床特征、外周血染色体核型分析、CNV及荧光定量PCR技术可有效确诊inv dup del(8p)综合征。     

15q11.2-13.2微重复四倍体综合征1例并文献复习

目的 采用分子遗传学技术分析1例常规染色体核型拟诊为21/22三体的发育迟缓伴孤独症患儿,明确遗传学诊断。方法 收集患儿及其父母的外周血标本,常规提取基因组DNA,应用高分辨染色体核型分析（400-550带）检测患儿及其父母的染色体数目及结构,微阵列比较基因组杂交技术(array-CGH)筛查患儿的全基因组拷贝数变异,以荧光原位杂交技术（FISH）对异常的基因拷贝进行染色体精确定位和定量。结果 女,2岁,发育迟缓伴孤独症样表现。外侧眼角下垂、内眦赘皮。常规染色体核型检查（320带）分别为47,XX,+22和47,XX,+21。高分辨染色体核型分析显示,该患儿携带额外标记染色体（SMC）,核型为47,XX,+mar dn,尚不能确定是否为21/22三体携带者,患儿父亲高分辨率核型染色体分析提示为46,XY,母亲为46,XX,提示患儿携带SMC为新生突变。array-CGH检测显示15q11.2-13.2区域微重复（chr15:22684529-30730543,8.0 Mb,hg19）。FISH验证该SMC来源于15号染色体,由15q11.2-13.2区域二倍体及双着丝粒组成。患儿最终诊断为15q11.2-13.2微重复四倍体综合征。复习文献报道的15q11.2-13.2拷贝数增加病例的临床表型,微重复四倍体综合征的主要表型有智力低下/发育迟缓（100％）、肌张力低下（92.9％）、孤独症/孤独症样表现（71.4％）和癫痫（61.5％）等。结论 15q11.2-13.2微重复四倍体综合征是患儿发生精神发育迟滞伴孤独症的遗传学基础,array-CGH能够快速、准确地检测基因组的微小失衡。     

6号环状染色体致隐匿性阴茎1例报告及文献复习

目的探讨6号环状染色体片段缺失与临床表型的关系。方法报道1例因隐匿性阴茎就诊男性患儿,通过常规染色体核型和全基因组染色体微阵列芯片技术,分析缺失片段位置及包含基因与临床表型的关系;同时进行文献复习。结果患儿染色体核型分析结果为6号环状染色体,全基因组染色体微阵列芯片检测发现,6号染色体短臂和长臂末端均存在缺失,del6p25.3p25.1.seq[GRCh37/hg39](204909-4210858)×1,del6q27.seq[GRCh37/hg39](170438227-170898549)×1,短臂p25区域缺失4.01 Mb,包含DUSP22、IRF4、EXOC2、HUS1B、LOC285768、FOXQ1、FOXF2、FOXC1等30个基因,而长臂6q27区域发生0.46 Mb缺失,包含LOC154449、DLL1、FAM120B、PSMB1、TBP、PDCD2等7个基因。分析比较本例患儿和文献报道的6号环状染色体病例,发现所有患儿均存在神经或生长发育障碍,但仅本例和另1例患儿有生殖道畸形。结论 6号环状染色体患者的临床表型与染色体缺失部位、缺失片段大小以及环状染色体稳定性密切相关。     

以身材矮小为突出表现的环状4号染色体1例报告及文献复习

目的探讨环状4号染色体病例的临床表型及发病机制。方法回顾分析1例以身材矮小为主要表现的环状4号染色体患儿的临床资料,并复习相关文献。结果女性患儿,10岁11个月,因身材矮小就诊,有颈蹼、乳头间距大,无明显智力障碍和其他畸形,生长激素分泌正常。染色体核型分析提示为环状4号染色体46,XX,r(4)(p16q35)。结论矮小症患儿需警惕环状染色体可能,染色体核型分析有助于确诊。     

以身材矮小为突出表现的环状 4 号染色体 1 例报告及文献复习#br#

目的探讨环状4号染色体病例的临床表型及发病机制。方法回顾分析1例以身材矮小为主要表现的环状4号染色体患儿的临床资料,并复习相关文献。结果女性患儿,10岁11个月,因身材矮小就诊,有颈蹼、乳头间距大,无明显智力障碍和其他畸形,生长激素分泌正常。染色体核型分析提示为环状4号染色体46,XX,r(4)(p16q35)。结论矮小症患儿需警惕环状染色体可能,染色体核型分析有助于确诊。     

一例15号额外标记染色体致智力障碍、难治性癫癎伴中枢性性早熟患者的临床及遗传学分析

15号额外标记染色体是一种罕见的染色体异常,本文报道1例15号额外标记染色体患儿,就其临床诊治经过及遗传缺陷进行研究。患儿,女,9岁半,自幼智力、运动发育落后,7岁出现乳房发育,8岁半出现癫癎发作：发作形式多样,多种抗癫癎药物控制欠佳,头颅磁共振未见异常,脑电图提示癎样放电频繁。采用G显带核型分析、荧光原位杂交（FISH）、甲基化多重连接依赖性探针扩增技术（甲基化MLPA）和微阵列比较基因组杂交（array-CGH）等多种遗传学检测手段,明确患儿存在新生的15q重复：15q11-13区域母源性拷贝数复制增加,基因组重排的形式为47,XX,+inv dup （15）（pter→q13：q13→pter）。15q11-13区域拷贝数复制增加与智力障碍、难治性癫癎伴中枢性性早熟临床表现密切相关。建议对于不明原因智力障碍伴癫癎患儿进行高分辨染色体核型分析。     

247例妊娠中，晚期羊水细胞产前诊断及异常核型分析

通过分析妊娠中,晚期胎儿羊水细胞染色体核型,了解该时期异常核型出现的频率,类型及与各种产前诊断指征的关系。从237例有产前诊断指征的孕妇,在妊娠13－34周行羊膜腔穿刺取羊水细胞培养,检查胎儿染色体核型。结果显示：羊膜腔穿刺247例,羊水细胞培养成功221例,成功率90％,检出染色体异常13例（5．9％）,其中,妊娠中期检出异常4．7％,（9／193）,妊娠晚期14．3％（4／28）,X2＝4．1,P＜0．05。染色体平衡重排（平衡易位,倒位）为主要的异常。／占异常核型的的46．2％（4／28）,X2＝4．1,P＜0．05。染色体平衡重排（平衡易位,倒位）为主要的异常,占异常核型的46．2％（6／13）,三体占异常核型30．8％（4／13）,46,XY,女性1例,46,XY／46,XY,t(9;15)1例,46,XX／46,XX,inv(2)1例,高龄孕妇异常检出率为6．3％（2／32）,非高龄组为5．8％（11／189）,P＞0．05,妊娠晚期羊水过多组异常检出率为10％（2／20）,IUGR异常检出率为20％（1／5）,可以结论：在有产前诊断指征的孕妇中,胎儿染色体异常的发生率为5．9％,平衡易位,倒位及部份三体为主要的染色体异常, 染色体平衡重排携带者,高龄孕孕妇,IUGR及羊水过多最常见的异常核型。     

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。     

Pallister-Killian综合征1例临床及细胞分子遗传学分析

目的探讨Pallister-Killian综合征(PKS)的细胞分子遗传学特点。方法采集患儿外周血标本进行G显带染色体核型分析,单核苷酸多态性-微阵列芯片(SNP array)技术鉴定异常片段来源,运用荧光原位杂交(FISH)技术加以确认。结果女性患儿,8月龄,因精神运动发育迟缓就诊。出生后有喂养困难、肌张力低下、面容异常、后发际线低、足部畸形、双耳听力未过关等临床表现。外周血染色体G显带核型为mos 47,XX,+mar[18]/46,XX[82];芯片分析结果发现患儿12号染色体短臂嵌合重复,提示为12 p四体嵌合体;FISH检测显示有48%的细胞有4个12 p信号。结论根据临床表现,常规外周血染色体核型分析结合SNP-array及FISH检测诊断PKS。     

A child with intellectual disability and dysmorphism due to complex ring chromosome 6: identification of molecular mechanism with review of literature

Background

Ring chromosome 6 (r(6)) is a rare disorder that mainly occurs as a ‘de novo’ event. Nonetheless, a wide phenotypic spectrum has been reported in r(6) cases, depending on breakpoints, size of involved region, copy number alterations and mosaicism of cells with r(6) and/or monosomy 6 due to loss of r(6).

Case presentation

An 11-year-old male was referred with developmental delay, intellectual disability and microcephaly. Physical examination revealed additionally short stature and multiple facial dysmorphisms. Banding cytogenetic studies revealed a karyotype of mos 46,XY,r(6)(p25.3q27)[54]/45,XY,-6[13]/46,XY,r(6)(::p25.3→q27::p25.3→q27::)[13]/46,XY[6]/47,XY,r(6)(p25.3q27)×2[2]dn. Additionally, molecular karyotyping and molecular cytogenetics confirmed the breakpoints and characterized a 1.3 Mb contiguous duplication at 6p25.3.

Conclusion

The present study has accurately identified copy number alterations caused by ring chromosome formation. A review of the literature suggests that hemizygous expression of TBP gene in 6q27~qter, is likely to be the underlying cause of the phenotype. The phenotypic correlation and clinical severity in r(6) cases continue to remain widely diverse in spite of numerous reports of genomic variations.

     

Congenital Diaphragmatic Hernia and Chromosomal Anomalies: Autopsy Study

In a 10-year review of autopsy records from Lutheran General Hospital (1992–2002), 13 cases of congenital diaphragmatic hernia (CDH) were found. The fetuses ranged between 21 and 35 wk of gestation. Four were born alive and five were diagnosed prenatally. The defect was left-sided in 11 cases. Cytogenetic study revealed five cases with normal karyotype and three cases with complex karyotypes. In five cases, no karyotype was performed. The three complex karyotypes were: 46,XX,del(8)(p23.1), 47,XX,+i(12)(p10)[6]/46XX[14] (Pallister-Killian syndrome), and 47,XY,+der(22)t(11:22)(q23.3:q11.2). The unbalanced translocation of chromosomes 11 and 22 in congenital diaphragmatic hernia has not been previously described. Three fetuses had heart abnormalities, including one which was associated with the 8p deletion. The other two had no karyotype study. Neither in this study, nor in the literature, is there a consistent or prevailing association between a specific chromosomal anomaly and CDH. The embryologic closure of the diaphragmatic leaflets may be mediated by a nonstructural chromosomal defect, more than one gene, and/or may be related to abnormalities not currently detectable. This study was presented at the College of American Pathologists Meeting, San Diego, California, USA, 10–14 September 2003.     

Novel translocation in acute megakaryoblastic leukemia (AML-M7)

The authors report a unique translocation in a patient with M7 acute myeloid leukemia and review the literature. A 22-month-old girl without Down syndrome was diagnosed with acute myeloid leukemia, subtype M7 (AML-M7), and died with relapsed disease following bone marrow transplantation. Tumor cells were evaluated using cytogenetics (including spectral karyotyping), immunohistochemistry, and flow cytometry. The patient was found to have a previously unreported complex translocation as follows: 50,XX,der(1)t(1;5)(p36?.1;p15?.1),del(5)(p15?.1), +6,+der(6;7)(?;?),der(7)t(6;7)(?;p22)[2],der(9)t(6;9) (?;p21)t(9;14)(q34;q11.2-q13),+10,t(12;16)(p13;q24),-14[2], del(14)(q13)[2],+der(19)t(1;19)(?;p13.3),+22[cp 4]. AML-M7 in non-Down syndrome patients is a rare disease that requires improved prognostic markers.     

Growth hormone neurosecretory dysfunction associated with ring chromosome 18

The patient was a girl 5 years and 1 month old of markedly short stature (–3.9 SD) for her chronological age. Although her karyotype was 46, XX, r(18)(p11q23), there were no symptoms of a chromosomal deletion. Other authors have described cases with a ring autosome showing a phenotype with short stature alone as ‘ring syndrome’, regardless of which autosome is involved. The present case seems to fall into this category. Although blood growth hormone (GH) showed normal responses to four types of provocative tests, the mean value of blood GH levels obtained at 30 min intervals for 24 h was low, indicating the existence of growth hormone neurosecretory dysfunction (GHND)     

13q-/r(13) mosaicism

A 2-month-old female infant with typical features of the 13q- syndrome was found to be a hitherto unreported mosaic consisting of 46,XX,del (13)(q22)/46,XX,r(13)(p13q22). She has not been able to maintain normal values of serum Na and Cl since the second day of life: this may be induced by cerebral dysgenesis.     

3q27 aberrations in a childhood ovary teratoma with associated malignant germ cell component

Cytogenetic studies of childhood ovary tumors have been poorly described. In the present article, the cytogenetic findings of an ovarian teratoma with malignant germ cell (yolk‐sac) component occurring in an 8‐year‐old female are detailed. GTG‐banding showed a karyotype of 46,XX, t(3;20)(q27;q13.3) [4]/46,XX, del3q27 [3]/46,XX [30]. Previous studies have demonstrated common sites of loss of heterozygosity at 3q27‐q28 region in different types of cancer, suggesting the presence of tumor suppressor genes within this region. Pediatr Blood Cancer 2009;52:398–401. © 2008 Wiley‐Liss, Inc.     

Primary Subcutaneous Primitive Neuroectodermal Tumor with Aggressive Behavior and an Unusual Karyotype: Case Report

Primitive neuroectodermal tumor/Ewing sarcoma (PNET/ES) rarely occurs in the skin and subcutaneous tissues. We present a case of a 16-year-old girl with primary cutaneous and subcutaneous PNET/ES of the abdominal wall. Despite wide local excision and chemotherapy, she rapidly developed cranial bone and brain metastases, followed by lung and skeletal metastases, and died shortly thereafter. The recurrent tumor exhibited light microscopic features of a small, round, blue cell tumor with intracytoplasmic glycogen. Immunohistochemical analysis showed positivity for CD99, CD56, S100, and glial fibrillary acid protein, and ultrastructural features included cytoplasmic glycogen and focal complex interdigitating synaptic junction-like cytoplasmic folds. Cytogenetic analysis of the relapsed tumor showed a complex karyotype: 47,XX,i(1)(q10), der(4)t(4;19) (q33q35;q13.1), + 8,t(15;17)(q24;p11.2p12),der(19)t (19;20)(q13.1;p11.2),der(22)t(20;22)(q13;q13). Cytogenetic, interphase fluorescence in situ hybridization, and molecular genetic analyses failed to show t(11:22) (q24;q12) or abnormalities of chromosome region 22q12. The clinical behavior and atypical and complex cytogenetic abnormalities exhibited by the tumor in this patient are unusual and represent the most aggressive end of the clinical spectrum of cutaneous and subcutaneous PNET/ES.     

The 11q- Syndrome with Mosaic Partial Deletion of 11q

A female child with mosaic partial deletion of 1 lq is reported. At 1 month of age she was presented with congenital glaucoma, trigonocephaly and multiple minor anomalies. She exhibited growth retardation and the typical phenotype of llq- syndrome. G-banding analysis failed to show any abnormality, although subsequent high resolution banding revealed the abnormal karyotype mos 46,XX,del(11)(q23.3 q24.2)/46,XX,del(11)(q23.3 q25). This case is a second case of mosaic llq- syndrome and her karyotype suggests that the region of 11q23.3–11q24.2 is critical in 11q- syndrome. Congenital glaucoma has never been reported as a complication of llq- syndrome.     

Cytogenetic Findings in Pediatric T-Lymphoblastic Lymphomas: One Institution’s Experience and a Review of the Literature

Cytogenetic analyses of lymphomas commonly reveal nonrandom chromosomal abnormalities, but there are relatively few reports in childhood lymphoblastic lymphoma (LL). We retrospectively reviewed G-banded karyotypic analyses performed at Arkansas Children’s Hospital between 1990 and 2004. Six children (2 to 20 years old) had LL that presented as mediastinal or cervical masses and had a T-cell immunophenotype and clonal abnormalities. The cytogenetic findings in these 6 patients were as follows: 46,XX,?7,inv(9)(p11q12),der (12)t(7;12)(q11.2;p13),t(16;18)(p13.1;q21),+22 in patient 1; 47,XX,+9,del(9)(q11q22)x2 in patient 2; 72?119, XY,+X,+1,+1, inv(2) (p11q13),?3,+5,+6,+7,+10,?12,?16, ?21,?21,?22,+mar in patient 3; 48,XY,+5,+20,t(7;9) (q32;q34) in patient 4; 47～48,XX,der(10)t(10;14)(q23; q11.2),+12, del(12)(p12)x2, ?14,del(16)(q22q22),+?add (19)(p13.3) in patient 5; and 48～49,XY,+7,+8,t(11;19) (q23;p?13.3),+der(19)t(11;19)[cp20] in patient 6. Eleven chromosome breakpoints in 6 of our patients (7q11, 12p13, 16p13, 18q21, 9q11, 2p11, 2q13, 7q32, and 7q23) have been reported in other patients with acute lymphoblastic leukemia or LL and involved regions containing TEL, ABL, E2A, MLL, and T-cell receptor-α genes. A review of the cytogenetic findings of these and other cases of LL reveals that clonal aberrations are common and most frequently involve T-cell receptor gene regions. The aberrations show some features similar to those of acute lymphoblastic leukemia and are not unique to LL, thus furnishing additional evidence of the equivalence of these two diseases. The cytogenetic features of LL may be helpful in the diagnosis of pediatric lymphomas and undifferentiated neoplasms.