Deciphering the molecular landscape of microcephaly in 87 Indian families by exome sequencing

Microcephaly is a frequent feature of neurodevelopmental disorders (NDDs). Our study presents the heterogeneous spectrum of genetic disorders in patients with microcephaly either in isolated form or in association with other neurological and extra-neural abnormalities. We present data of 91 patients from 87 unrelated families referred to our clinic during 2016–2020 and provide a comprehensive clinical and genetic landscape in the studied cohort. Molecular diagnosis using exome sequencing was made in 45 families giving a yield of 51.7%. In 9 additional families probable causative variants were detected. We identified disease causing variations in 49 genes that are involved in different functional pathways Among these, 36 had an autosomal recessive pattern, 8 had an autosomal dominant pattern (all inherited de novo), and 5 had an X-linked pattern. In 41 probands where sequence variations in autosomal recessive genes were identified 31 were homozygotes (including 16 from non-consanguineous families). The study added 28 novel pathogenic/likely pathogenic variations. The study also calls attention to phenotypic variability and expansion in spectrum as well as uncovers genes where microcephaly is not reported previously or is a rare finding. We here report phenotypes associated with the genes for ultra-rare NDDs with microcephaly namely ATRIP, MINPP1, PNPLA8, AIMP2, ANKLE2, NCAPD2 and TRIT1.     

132例男性不育患者遗传学病因分析

目的：对男性不育患者进行遗传学病因分析，并探讨其遗传效应。方法：采取132例男性不育患者外周血进行染色体核型分析。结果：132例男性不育患者中，染色体异常24例，染色体变异22例。其中大Y20例，47，XXY18例，45．XY，t(13；14)3例，小Y和46，XY，inv(9)各2例，46，XY，t(9；22)1例。结论：染色体异常是男性不育的重要原因，并建议男性不育患者进行基因诊断，以便确诊是否属于遗传病，为生育提供指导，避免盲目治疗。     

基于Internet的遗传疾病登记、随访系统的设计与实现

本系统通过以Internet网为平台,将传统的医院/患者(咨询者)的遗传随访模式转为医院/Internet网/患者(咨询者)的新医疗模式,该系统会大大提高遗传随访的及时性和便利性;同时,会有利于遗传登记的开展,也有利于随访资料的保存。     

Familial Sneddon's syndrome

We report the familial occurrence and apparent autosomal dominant inheritance of Sneddon's syndrome with variable clinical expression. The proband, a 40-year-old woman, presented with livedo reticularis and progressive neurological deterioration following a stroke. The diagnosis was confirmed by cerebral angiogram and skin biopsy, both showing the characteristic findings. Two of the patient's sisters were reported to have been similarly affected in the past. Her mother, two additional siblings and five of her seven children exhibited various vasospastic skin phenomena. Familial aggregation of this disorder may be common and a genetic basis may be involved in its pathogenesis.     

Genetic contributions to Parkinson's disease

Sporadic Parkinson's disease (PD) is a common neurodegenerative disorder, characterized by the loss of midbrain dopamine neurons and Lewy body inclusions. It is thought to result from a complex interaction between multiple predisposing genes and environmental influences, although these interactions are still poorly understood. Several causative genes have been identified in different families. Mutations in two genes [α-synuclein and nuclear receptor-related 1 (Nurr1)] cause the same pathology, and a third locus on chromosome 2 also causes this pathology. Other familial PD mutations have identified genes involved in the ubiquitin–proteasome system [parkin and ubiquitin C-terminal hydroxylase L1 (UCHL1)], although such cases do not produce Lewy bodies. These studies highlight critical cellular proteins and mechanisms for dopamine neuron survival as disrupted in Parkinson's disease. Understanding the genetic variations impacting on dopamine neurons may illuminate other molecular mechanisms involved. Additional candidate genes involved in dopamine cell survival, dopamine synthesis, metabolism and function, energy supply, oxidative stress, and cellular detoxification have been indicated by transgenic animal models and/or screened in human populations with differing results. Genetic variation in genes known to produce different patterns and types of neurodegeneration that may impact on the function of dopamine neurons are also reviewed. These studies suggest that environment and genetic background are likely to have a significant influence on susceptibility to Parkinson's disease. The identification of multiple genes predisposing to Parkinson's disease will assist in determining the cellular pathway/s leading to the neurodegeneration observed in this disease.     

Breast Cancer Risk Assessment and Counseling: A Clinician's Guide

Abstract: Most individuals concerned about hereditary breast cancer risk will neither order nor benefit from genetic testing at the present time. Many will, however, seek information about their risk and testing. Risk assessment services, in addition to providing information about hereditary risk and genetic testing, need also to include assessment of non-hereditary risks, information about how to evaluate risks, early detection modalities, the etiology of cancer, and assistance in devising follow-up health care plans. Psychosocial factors, particularly those pertaining to the individual's past history with illness and beliefs about causes and prognosis, must be taken into account to provide relevant information that is understood. A case history with examples of some of the types of information that lead to informed consent in a cancer risk assessment setting is provided.     

综合医院心理咨询门诊儿童咨客分析

目的；了解综合医院心理咨询门诊儿童咨客的特点。方法：总结中山大学附属三院心理咨询门诊近3年儿童咨客的资料。结果：咨客男女比例为1．96：1，咨客人数随着年龄的增长而增加，女童中13－16岁的比例男童大，5－8岁和9－12岁的比例较男童小。广州市内外的咨客比例为1．38：1，不同年龄儿童咨客的居住地构成是有差异的。最常见的病种是精神分裂症，神经症、精神发育迟滞，儿童多动症，单纯咨询和品行障碍，不同年龄，不同性别的儿童咨客的疾病构成是有差异的。结论：综合医院心理咨询门诊与儿童心理咨询门诊的儿童咨客是有差异的。     

利培酮治疗与细胞色素P4502D6/C188T酶基因多态性的关联分析

目的　研究利培酮临床效应的个体差异与其代谢酶细胞色素P4 5 0 2D6 (cytochromeP4 5 02D6 ,CYP2D6 )酶基因多态性的相关性。方法　对 88例符合CCMD 3精神分裂症诊断标准的患者和 96例健康对照者作病例 -对照分析。精神分裂症患者给予利培酮治疗 8周 ,用阳性和阴性症状量表 (posi tiveandnegativesymptomscale ,PANSS)评分评价利培酮疗效。采用聚合酶链反应扩增及限制性片段长度多态性 (PCR RFLP)技术对CYP2D6exonⅠ的C188T位点突变进行检测 ,分析利培酮临床效应与其主要代谢酶CYP2D6 /C188T酶基因多态性的相关性。结果　中国上海地区人群的CYP2D6 /C188T突变率(弱代谢型 )为 36 .3% ,病例组和正常对照组间基因型频率总体分布比较无显著差异 (χ2 =1.15 ,df=2 ,P >0 .0 5 ) ,两组间的等位基因频率之间比较也无显著性差异 (χ2 =0 .78,df=1,P >0 .0 5 )。进行性别及有否家族史分组后分析 ,亦无差异存在 ,且CYP2D6 /C188T突变与利培酮临床效应之间并无相关性 (χ2 =1.12 ,df=2 ;χ2 =0 .0 3,df=1,P >0 .0 5 )。结论　未发现中国人CYP2D6 /C188T多态性与利培酮临床效应的个体差异有相关性。     

全自动遗传分析系统的原理及其临床应用

全自动核酸测序分析系统具有遗传信息检测和分析功能,随其应用范围增加,开始进入临床。本文介绍了该仪器的工作原理、结构、功能、操作要点以及临床医学应用。     

Clinical impact of CCM mutation detection in familial cavernous angioma

Introduction and background A 3-year-old Bosnian girl with a large symptomatic brainstem and multiple supratentorial cavernous angiomas, who underwent neurosurgical treatment, is presented. As multiple cavernomas are more common in familial cases, genetic analyses and neuroradiological imaging were performed in the patient and her parents to see whether there was any evidence for inheritance. This information is important for genetic counseling and provision of medical care for at-risk relatives. Currently, no recommendation is available on how to manage these cases.Results Genetic analyses demonstrated a novel CCM1 frameshift mutation (c.1683_1684insA; p.V562SfsX6) in the child and the asymptomatic 27-year-old mother. Sensitive gradient-echo magnetic resonance imaging of the mother revealed multiple supratentorial lesions, whereas analogous imaging of the father showed no pathological findings.Conclusion This case exemplifies that seemingly sporadic cases with multiple lesions might well be hereditary and that presymptomatic genetic testing of family members may identify relatives for whom clinical and neuroradiological monitoring is indicated.