小额外标记染色体与不育的研究进展（英文）

不育受年龄、激素水平、病毒感染、免疫、遗传、手术创伤以及配子异常等因素影响。回顾文献发现,染色体畸变与不育密切相关。不育患者小额外标记染色体(sSMC)的携带率约是正常人群的3倍。根据sSMC数据库(http://ssmc-tl.com/Start.html)收录,已有225个病例研究发现sSMC主要来源于15号或14号染色体。不育患者的sSMC中,53%是通过遗传获得,且更倾向于来自母亲。同时,sSMC的遗传有一定的性别差异,携带有sSMC的母亲更倾向于遗传给儿子,反之,携带有sSMC父亲更倾向于遗传给女儿。少弱畸精子症患者携带的sSMC多数来源于近端着丝粒染色体,而反复自然流产夫妇携带的sSMC大多来自非近端着丝粒染色体。本文全面综述目前sSMC与不育相关性研究,有助于理解遗传异常在不育发生过程中的作用。

Germline MLH1 and MSH2 mutational spectrum including frequent large genomic aberrations in Hungarian hereditary non-polyposis colorectal cancer families:Implications for genetic testing

AIM: To analyze the prevalence of germline MLH1 and MSH2 gene mutations and evaluate the clinical characteristics of Hungarian hereditary non-polyposis colorectal cancer (HNPCC) families. METHODS: Thirty-six kindreds were tested for mutations using conformation sensitive gel electrophoreses, direct sequencing and also screening for genomic rearrangements applying multiplex ligation-dependent probe amplifi cation (MLPA). RESULTS: Eighteen germline mutations (50%) were identifi ed, 9 in MLH1 and 9 in MSH2. Sixteen of these sequence alterations were considered pathogenic, the remaining two were non-conservative missense alterations occurring at highly conserved functional motifs. The majority of the defi nite pathogenic mutations (81%, 13/16) were found in families fulfilling the stringent Amsterdam Ⅰ/Ⅱ criteria, including three rearrangements revealed by MLPA (two in MSH2 and one in MLH1). However, in three out of sixteen HNPCC-suspected families (19%), a disease-causing alteration could be revealed. Furthermore, nine mutations described here are novel, and none of the sequence changes were found in more than one family.CONCLUSION: Our study describes for the f irst time the prevalence and spectrum of germline mismatch repair gene mutations in Hungarian HNPCC and suspected-HNPCC families. The results presented here suggest that clinical selection criteria should be relaxed and detection of genomic rearrangements should be included in genetic screening in this population.

Cytogenetic Diagnosis and Analysis of the Clinical Profile of Individuals with Non-down Syndrome Intellectual Disability

Chromosomal alterations are the main causes of genetic diseases. One of the characteristics of certain genetic syndromes is ID （intellectual disability） presented by the individual in varying degrees. The study of the ID, its etiology, association or not with chromosomal abnormalities and a clinical diagnosis associated with the examination of karyotype are important aspects to consider when providing genetic counseling for families. Due to the lack of similar studies and of easy access to cytogenetic services for the Amazonian population, this study aimed to contribute to the advancement of this line of study in the state, analyzing the karyotype of individuals with ID, not Down Syndrome treated at the APAE-Manaus and identifying the main types of chromosomal alterations in the individuals analyzed. Analyzes were performed of the clinical diagnosis through investigation of the data from the interview and medical records as well as analysis of the karyotype of 31 patients with non-Down syndrome ID, attended in the APAE-Manaus. Of these subjects, 20 were female and 11 male. The results showed only 2 cases of chromosome abnormalities are detectable by classical cytogenetics, one of mosaic Turner syndrome and one a heterochromatic variant. It is therefore necessary to complement the study with the addition of molecular techniques for the investigation of microdeletions and/or other alterations not detectable through the banding technique, mainly for individuals whose dysmorphisms indicate a suspected syndrome.