An interstitial,apparently-balanced chromosomal insertion in the etiology of Langer–Giedion syndrome in an Asian family

Langer–Giedion syndrome (LGS; MIM 150230), also called trichorhinophalangeal syndrome type II (TRPS2), is a contiguous gene syndrome caused by a one-copy deletion in the chromosome 8q23-q24 region, spanning the genes TRPS1 and EXT1. We identified an LGS family with two affected and two unaffected siblings from unaffected parents. To investigate the etiology of recurrence of LGS in this family, array CGH was performed on all family members. We identified a 7.29 Mb interstitial deletion at chromosome region 8q23-q24 in the two affected siblings, but no such deletion in the unaffected family members. However, the mother and one of the two unaffected siblings carried a 1.29 Mb deletion at chromosome region 8q24.1, sharing the distal breakpoint with the larger deleted segment found in the affected siblings. Another unaffected sibling had a 6.0 Mb duplication, sharing the proximal breakpoint of the deletion in the affected siblings. Karyotypic and FISH analyses in the unaffected mother revealed an insertional translocation of 8q23-q24 genomic material into chromosome 13: 46,XX,ins(13;8)(q33;q23q24). This insertional translocation in the mother results in the recurrence of LGS in this family, highlighting the importance of submicroscopic rearrangements in the genetic counseling for LGS.     

Successful PGD cycles for mosaic Robertsonian translocation carriers provide insights into the mechanism of formation of the derivative chromosomes

Preimplantation genetic diagnosis (PGD) has been carried out for two couples with different mosaic Robertsonian translocations. Two PGD cycles for a mosaic 13;13 homologous Robertsonian translocation carrier resulted in the birth of a healthy child in each cycle, illustrating the importance of scanning G‐banded preparations from homologous Robertsonian carriers for the presence of a normal cell line. One couple was referred for PGD because the male partner carried a mosaic 14;15 Robertsonian translocation with a normal cell line. A single PGD cycle resulted in the birth of a healthy child. Follow‐up studies and extended FISH analysis of the carrier's lymphocytes detected three cell lines, two carrying different 14;15 Robertsonian chromosomes and one normal cell line. The two 14;15 Robertsonian chromosomes had different breakpoints in the proximal short arm regions. We suggest that the presence of the D15Z1 polymorphism on the short arm of one chromosome 14 mediated the post‐zygotic formation of the two different Robertsonian chromosomes. © 2013 Wiley Periodicals, Inc.     

初次全髋关节置换术前胶片模板测量与评估

目的：通过胶片模板测量进行全髋关节置换术前计划、术后重复测量评估探讨胶片模板测量在全髋关节置换术前计划中的准确性和重要性。方法：2012年3月至2012年8月,收集我科同一位高年资医师行全髋关节置换病例72例（84髋）作研究对象。术前通过胶片模板测量,决定股骨颈截骨位置,计划髋臼、股骨柄、股骨头假体型号以及植入位置,调整双下肢长度;术后通过重复测量对术前计划进行评估和验证。结果：所有病例股骨颈截骨位置与术前计划相差均在5mm范围内,其中相差小于3mm者占84．5％。术前肢体平均短缩10mm（0～35mm）,术后肢体平均短缩3mm（0-11mm）,差异有统计学意义;术后双下肢长度相差在5mm以内者占90．5％。术前模板测量出的假体型号与实际应用的假体比较,髋臼假体完全符合率65．4％、相差1个型号以内的符合率为94．0％;股骨假体完全符合率为83．3％、相差1个型号以内的符合率为96．4％;股骨头假体完全符合率为63．1％、相差1个型号以内的符合率为98．8％。结论：全髋关节置换术前胶片模板测量对于术中假体型号选择具有较好的预测作用,对于假体位置安放以及双下肢长度调整均具有重要意义。     

Partial trisomy 6p from a de novo translocation (6; 18) with variable mosaicism in different tissues

Partial trisomy 6p is regarded as a distinct phenotype with short stature, failure to thrive, facial dysmorphisms with blepharophimosis, mental retardation and other malformations. An 18-month-old girl with typical features of partial trisomy 6p showed a de novo unbalanced translocation resulting in partial trisomy 6p21 to pter and partial monosomy 18p11 to pter. The translocation was observed in all fibroblasts analyzed, but only in 6% of the peripheral lymphocytes.     

Inherited balanced translocation t(9;17)(q33.2;q25.3) concomitant with a 16p13.1 duplication in a patient with schizophrenia

We report two rare genetic aberrations in a schizophrenia patient that may act together to confer disease susceptibility. A previously unreported balanced t(9;17)(q33.2;q25.3) translocation was observed in two schizophrenia‐affected members of a small family with diverse psychiatric disorders. The proband also carried a 1.5 Mbp microduplication at 16p13.1 that could not be investigated in other family members. The duplication has been reported to predispose to schizophrenia, autism and mental retardation, with incomplete penetrance and variable expressivity. The t(9;17) (q33.2;q25.3) translocation breakpoint occurs within the open reading frames of KIAA1618 on 17q25.3, and TTLL11 (tyrosine tubulin ligase like 11) on 9q33.2, causing no change in the expression level of KIAA1618 but leading to loss of expression of one TTLL11 allele. TTLL11 belongs to a family of enzymes catalyzing polyglutamylation, an unusual neuron‐specific post‐translational modification of microtubule proteins, which modulates microtubule development and dynamics. The 16p13.1 duplication resulted in increased expression of NDE1, encoding a DISC1 protein partner mediating DISC1 functions in microtubule dynamics. We hypothesize that concomitant TTLL11‐NDE1 deregulation may increase mutation load, among others, also on the DISC1 pathway, which could contribute to disease pathogenesis through multiple effects on neuronal development, synaptic plasticity, and neurotransmission. Our data illustrate the difficulties in interpreting the contribution of multiple potentially pathogenic changes likely to emerge in future next‐generation sequencing studies, where access to extended families will be increasingly important. © 2011 Wiley‐Liss, Inc.     

Subtelomeric monosomy 11q and trisomy 16q in siblings and an unrelated child: molecular characterization of two der(11)t(11;16)

We report here three children with a der(11)t(11;16), two sibs (patients 1 and 2) having inherited a recombinant chromosome from a maternal t(11;16)(q24.3;q23.2) and a third unrelated child with a de novo der(11)t(11;16)(q25;q22.1), leading to partial monosomy 11q and trisomy 16q. Fluorescent in situ hybridization (FISH) using bacterial artificial chromosome (BAC) clones and array‐CGH were performed to determine the breakpoints involved in the familial and the de novo rearrangements. The partial 11 monosomy extended from 11q24.3 to 11qter and measured 6.17–6.21 Mb in Patients 1 and 2 while the size of the partial 11q25‐>qter monosomy was estimated at 1.97–2.11 Mb for Patient 3. The partial 16 trisomy extended from 16q23.2 to 16qter and measured 8.93–8.95 Mb in Patients 1 and 2 while the size of the partial 16q22.1‐>qter trisomy was 20.82 Mb for Patient 3. Intraventricular hemorrhage and transitional thrombocytopenia were found in both sibs but not in the third patient. The FLI1 gene, which is the most relevant gene for thrombocytopenia in Jacobsen syndrome, was neither deleted in family A nor in Patient 3. We suggest that a positional effect could affect the FLI1 expression for these two sibs. Deafness of our three patients confirmed the association of this anomaly to 11q monosomy and tended to confirm the hypothetic role of DFNB20 in Jacobsen syndrome hearing loss. Both sibs shared most of the features commonly observed in Jacobsen syndrome, but not the third patient. This confirmed that terminal 11q trisomy spanning 1 to 1.97–2.11 Mb is not associated with a typical Jacobsen syndrome. © 2011 Wiley‐Liss, Inc.     

Predominant DNMT and TET mediate effects of allergen on the human bronchial epithelium in a controlled air pollution exposure study

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一例母源性46,Y,der(X)t(X;Y)(p22;q11)染色体非平衡易位患儿的遗传学分析

目的对1例临床表征为身材矮小、鼻根部内陷、双侧隐睾、智力低下患儿进行遗传学分析,探讨该染色体结构异常与临床表征之间的关系。方法应用G显带染色体核型分析及染色体微阵列分析(chromosomal microarray analysis,CMA)技术对患儿进行遗传学检测,并对其父母进行外周血染色体核型分析。结果G显带分析结果显示患儿染色体核型为46,Y,der(X)t(X;Y)(p22;q11),mat。CMA检测结果提示患儿X染色体短臂Xp22.33p22.31存在约8.3 Mb片段缺失,Y染色体长臂Yq11.221qter存在约43.3 Mb片段重复。其父亲染色体核型正常,母亲染色体核型结果为46,X,der(X)t(X;Y)(p22;q11)。结论患儿携带母源性der(X)t(X;Y)(p22;q11)染色体非平衡易位,携带者的表型与其性别以及X染色体缺失片段的大小和位置密切相关。男性携带者智力障碍、生长发育落后等异常表型较女性更为严重。     

MicroRNA-146b-5p suppresses cholangiocarcinoma cells by targeting TRAF6 and modulating p53 translocation

BackgroundIn view of the poor prognosis and high mortality of cholangiocarcinoma, there is a need for new therapeutic strategies. This study aims to reveal the biological function of miR-146b-5p in cholangiocarcinoma cell and its possible mechanism.MethodsThe expression level and prognostic information on miR-146b-5p in cholangiocarcinoma were obtained in TCGA database. The biological function of miR-146b-5p on proliferation and vitality of cholangiocarcinoma cell HUCCT-1 was examined by EdU and MTT assay, and the apoptosis of HUCCT-1 cells transfected with miR-146b-5p mimic, mimic control, inhibitor, inhibitor control was detected by flow cytometry analysis. The western blot was done to evaluate the effect of miR-146b-5p targeting substrate and the expression of p53 in whole-cell protein and mitochondria fractions.ResultsOur finding revealed that miR-146b-5p expression in patients with CHOL was lower than the normal group(p＜0.001). MiR-146b-5p expression was down-regulated in human cholangiocarcinoma HUCCT-1 and RBE cells compared to normal control HIBEC and other cancer cells. The miR-146b-5p mimic could inhibit HUCCT-1 cell proliferation (p＜0.05) and promote HUCCT-1 cell apoptosis significantly (p＜0.05). The results of western blot showed that miR-146b-5p mimic could directly target TRAF6 3′UTR region and up-regulate the expression of p53 in mitochondria and miR-146b-5p inhibitor could down-regulated the level of p53 in mitochondria.ConclusionMiR-146b-5p is a cholangiocarcinoma suppressor by inhibiting cell proliferation and promoting cell apoptosis with targeting TRAF6, possibly via modulating p53 translocation to mitochondria.     

Identification ofDrosophila mutant with memory defects after acquisition of conditioned reflex suppression of courtship

Four lines were selected from a collection of 33 lines prepared by P insertion mutagenesis using a single-copy P-element system; the males of these four lines showed memory defects after acquisition of conditioned reflex suppression of courting. In two lines (P171 and P95), the dynamics of retention of the conditioned reflex in the repeated impregnated-female courting test were similar to those of known short-term memory mutantsdnc andrut. In line P153, the dynamics were more reminiscent of the memory dynamics in a known medium-term memory mutant,amn. In line P124, the learning index was insignificant immediately after training was completed, which may indicate that this line was unable to acquire conditioned reflex suppression of courting. Determination of the positions of the P elements (P171: 48A-B; P153: 49B-C; P124; 67B–68A; P95: 77C-D) showed no correspondence with previously known mutations producing memory lesions. Translated from Rossiiskii Fiziologicheskii Zhurnal imeni I. M. Sechenova, Vol. 85, No. 1, pp. 84–92, January, 1999.