染色体平衡易位与异常孕产

目的探讨染色体平衡易位与异常孕产的关系。方法采用外周血淋巴细胞培养和染色体G显带分析,对612对有异常孕产史的夫妇进行染色体检查。结果染色体平衡易位携带者检出率为3．3％(41／1 224),其中常染色体相互易位占58．5％(24／41),罗伯逊易位占39．0％(16／41),嵌合易位占2．4％(1／41)。9例为世界首报染色体异常核型,分别为:46,XY,t(11;12)(q13;q21);46,XX,t(3;20) (qll;q11);46,XX,t(15;16)(pll;q13);46,XY,t(2;14)(p16;q31);46,XY,t(4;10)(q25;p15);46,XX,t(3;8) (p26;q11);46,XY,t(6;16)(q15;p13);46,XX,t(18;22)(p10;q10);46,XY,t(18;22)(p10;q10)mat。总妊娠127次,早期妊娠流产率为86．6％(110／127)。结论染色体平衡易位携带者的异常孕产以早期妊娠自然流产为主要表现。     

染色体异常在男性不育中的诊断意义

目的:分析研究染色体异常在男性不育中的诊断意义。方法:应用细胞遗传学实验技术检查男性不育症染色体共579例。结果:染色体异常与无精症明显相关,与少弱精症有相关性;性腺激素在生精功能受损时,出现明显变化,一般不是男性不育的直接原因。结论:染色体异常是造成不育重要因素。性腺激素在男性不育诊断及分类方面具有重要作用。     

Posterior amorphous corneal dystrophy caused by a de novo deletion

We present a newborn diagnosed with posterior amorphous corneal dystrophy (PACD). PACD is a rare disorder with partial or complete posterior lamellar corneal opacification. Genetic screening showed a deletion of chromosome 12q21.33-q22 containing the identified four small leucine-rich proteoglycans (SLRP’s) associated with this particular dystrophy. Neither parents were carrier of the deletion. To our knowledge, this is the first report of a de novo mutation causing PACD.     

妊娠中期鼻骨发育异常胎儿的染色体检测结果及相关因素分析

背景　胎儿鼻骨发育情况评估作为常规产前超声检查项目，是胎儿染色体检查的重要指标，近几年染色体微阵列分析技术（CMA）的应用使得产前胎儿染色体疾病的检查范围更广、准确度更高，在此基础上有必要对鼻骨发育异常和染色体异常之间的相关性重新进行总结，为临床提供参考。目的　探讨胎儿鼻骨发育异常或与其他产前筛查高危因素结合在预测胎儿染色体异常中的价值，以及CMA在胎儿鼻骨发育异常遗传学检测中的应用价值。方法　选取2016年12月-2020年1月于内蒙古自治区妇幼保健院进行产前超声检查并提示胎儿鼻骨缺失或发育不良的92例孕妇及胎儿为研究对象。收集其产检信息、遗传学检测结果及妊娠结局。遗传学检测方法包括染色体核型分析和CMA。结果　染色体核型分析检出染色体异常19例（20.7%），均为21-三体；CMA检出染色体异常25例（27.2%），包括21-三体19例，染色体微缺失微重复6例。孤立性与非孤立性鼻骨发育异常胎儿染色体异常发生率比较，差异无统计学意义（P>0.05）。与单纯孤立性鼻骨发育异常胎儿相比，孤立性鼻骨发育异常+颈项透明层（NT）增厚、孤立性鼻骨发育异常+血清学筛查（MSS）高风险、孤立性鼻骨发育异常+无创产前筛查（NIPT）高风险、孤立性鼻骨发育异常+2种及以上产前筛查高危因素胎儿染色体异常发生率均升高（P<0.05）。结论　鼻骨缺失或发育不良的胎儿染色体异常发生率较高，且与基因组变异有关；染色体核型分析、CMA结合其他产前筛查高危因素将有效提高染色体异常的检出率。CMA的应用为产前诊断提供了更多的染色体变异信息，建议所有类型的胎儿鼻骨缺失或发育不良进行染色体核型分析与CMA结合的遗传学检测。     

Prenatal diagnosis of complex phenotype in a 13-week-old fetus with an interstitial multigene deletion 20q13.13.-q13.2 by chromosomal microarray

We report the first trimester three-dimensional ultrasonographic findings in a 13-week-old fetus with complex phenotype and a de novo 4.7 Mb multigene deletion encompassing chromosome region 20q13.13-q13.2 detected by chromosomal microarray. Fetal sonography detected radial-ray anomalies in the form of bilateral absence of thumbs and the left club hand deformity. The presence of single atrioventricular canal instead of the atrial septal defect typical for Holt-Oram syndrome pointed us to rather suspect the SALL4 related diseases. Central nervous system anomaly in the form of enlarged lateral brain ventricles with choroid plexus shifted backwards was not previously reported as a part of SALL4 related disorders. The pregnancy was terminated at 14 + 3 weeks of pregnancy and the autopsy confirmed ultrasonographic findings. Deleted region included 38 genes, where only SALL4, ADNP and KCNB1 heterozygote pathogenic variants were described to be cause of syndromic forms. Radial ray anomalies are common part of clinical picture of SALL4 related disorders. Despite the lack of prenatally described cases, we hypothesized that maldevelopment of lateral brain ventriculomegaly could be very early sonographic sign of disturbed ADNP expression causing Helsmoortel-Van der Aa syndrome, but in some extent also of KCNB1 related early-onset epileptic encephalopathy. Furthermore, the possible dosage-dependent influence of recessive genes located in this region cannot be also excluded. The use of genome-wide technologies enables the detection of subtle chromosomal imbalances and more precise familial genetic counseling regarding actual and future pregnancies.     

Dosage effects of X and Y chromosomes on language and social functioning in children with supernumerary sex chromosome aneuploidies: implications for idiopathic language impairment and autism spectrum disorders

Background: Supernumerary sex chromosome aneuploidies (X/Y‐aneuploidies), the presence of extra X and/or Y chromosomes, are associated with heightened rates of language impairments and social difficulties. However, no single study has examined different language domains and social functioning in the same sample of children with tri‐, tetra‐, and pentasomy X/Y‐aneuploidy. The current research sought to fill this gap in the literature and to examine dosage effects of X and Y chromosomes on language and social functioning. Methods: Participants included 110 youth with X/Y‐aneuploidies (32 female) and 52 with typical development (25 female) matched on age (mean ～12 years; range 4–22) and maternal education. Participants completed the Wechsler intelligence scales, and parents completed the Children’s Communication Checklist‐2 and the Social Responsiveness Scale to assess language skills and autistic traits, respectively. Results: Both supernumerary X and Y chromosomes were related to depressed structural and pragmatic language skills and increased autistic traits. The addition of a Y chromosome had a disproportionately greater impact on pragmatic language; the addition of one or more X chromosomes had a disproportionately greater impact on structural language. Conclusions: Given that we link extra X chromosomes with structural language impairments and an extra Y chromosome with pragmatic language impairments, X/Y‐aneuploidies may provide clues to genetic mechanisms contributing to idiopathic language impairment and autism spectrum disorders.