Genetic effects of a 13q31.1 microdeletion detected by noninvasive prenatal testing (NIPT)

Microdeletions of chromosome 13q31.1 are relatively rare. These types of deletions may cause different genetic effects on genotypes and/or phenotypes. There are several ways to detect microdeletions; noninvasive prenatal testing (NIPT) is the newest detection method. In this study, we aimed to investigate the genetic effects of a 13q31.1 microdeletion detected by NIPT and to reconfirm the feasibility of this procedure in predicting sub-chromosomal copy number variations (CNVs). The 13q31.1 microdeletion, which has previously been described as a disease-associated fragment, was detected by NIPT in a pregnant woman. To validate the finding and to explain the origin of this sub-chromosomal CNV, we collected fetal amniotic fluid and parental blood samples and tested the samples using array-based comparative genomic hybridization (aCGH). Karyotype analysis was performed on all of the samples to rule out balanced or mosaic anomalies. The aCGH results confirmed the NIPT findings. We detected the same type of microdeletion in the fetus and the mother via aCGH. The mother had a normal phenotype; therefore, in a post-test genetic counseling session, we predicted a normal phenotype for the fetus. After delivery, the normal phenotype of the newborn confirmed our prediction. Based on the present study, this 13q31.1 microdeletion may be considered as a chromosomal polymorphism. This study also reconfirmed the feasibility of obtaining a molecular karyotype of a fetus via NIPT.     

以甲状旁腺功能减退为表型的DiGeorge 综合征1 例及文献复习

目的探索22q11.2微缺失综合征的临床表型及治疗经验。方法总结兰州大学第一医院儿内科2020年6月收治的1例以甲状旁腺功能减退为表型的DiGeorge综合征的诊治过程,并复习总结国内外相关病例的诊疗过程。结果病儿主诉间断可疑抽搐10余天。入院完善相关检查以及基因检测后,诊断为DiGeorge综合征伴甲状旁腺功能减退、继发性癫痫;经给予钙剂、骨化三醇及左乙拉西坦等对症治疗,病儿病情好转后出院,院外随访半年内病儿无抽搐发作。结论补钙是目前治疗以甲状旁腺功能减退为表型的DiGeorge综合征的关键措施。     

Delineating the 17q24.2–q24.3 microdeletion syndrome phenotype

We present an 11-year-old girl with a 2.3 Mb de novo interstitial deletion in chromosome 17q24.2–q24.3 identified by array CGH. The phenotype in this case includes skeletal malformations (lower limb bowing, progressive scoliosis and dental abnormalities), feeding problems, mild learning difficulties, and a characteristic facial appearance. Much of the phenotype is attributable to the deletion of KCNJ2, which causes Andersen Tawil Syndrome (ATS), but the facial appearance is not typical. We hypothesise that the presence of mild channelopathy-related features seen in ATS may be explained by haplo-insufficiency, leading to a reduced number of functionally normal Kir2.1 channels. Comparison is made to previous reports describing overlapping 17q deletions, and potential candidate genes which account for the specific phenotypic similarities with this case are highlighted.     

AZF微缺失与生精障碍症的研究分析

目的探讨Y染色体AZF微缺失与生精障碍症(男性原发性无精子症和少精子症)之间的关系。方法采用多重聚合酶链反应技术对158例生精障碍症患者(包括健康男性50例)进行AZFa、AZFb、AZFc和AZFd四个区域微缺失分析。结果 158例生精障碍症患者中发现AZF微缺失21例,总缺失率为13.3%。结论 Y染色体AZF区域微缺失与男性生精障碍症有着明显的相关性,因此有必要对生殖门诊及准备行辅助生育技术的生精障碍症患者行Y染色体AZF微缺失检测,其对该症的诊断及治疗具有重要的意义。     

Do microdeletions in the AZF region of the Y chromosome accompany cryptorchidism in Turkish children?

OBJECTIVE: To investigate the presence of Y chromosome microdeletions in children with cryptorchidism. MATERIALS AND METHODS: Male patients aged between 1 and 17 years, who had been diagnosed by physical examination to have cryptorchid testes, were included in the study. Microdeletions of 24 gene loci belonging to the AZF-a, AZF-b and AZF-c regions of the Y chromosome were examined by multiplex polymerase chain reaction (PCR) multiplication of the DNA sample extracted from peripheral leukocytes. RESULTS: Sixty-four patients with a mean age of 7.82+/-3.21 (range: 1-17) years were included in the study. There was unilateral cryptorchidism in 53.1% (34/64) of the patients and bilateral cryptorchidism in 46.8% (30/48) of the patients. No microdeletion of gene loci on the AZF-a, AZF-b and AZF-c regions of the Y chromosome was determined in any patient. CONCLUSION: Studies on Y chromosome microdeletions are important due to a potential for the transmission of genetic abnormalities to offspring. Assisted reproduction techniques may cause the transmission of genetic abnormalities to offspring because the physiological fertilisation mechanism is bypassed. It was found that there was probably no aetiologic correlation between microdeletions in gene loci on the AZF-a, AZF-b and AZF-c regions of the Y chromosome and cryptorchidism.     

多重聚合酶链反应检测Y染色体无精子因子微缺失

目的:研究原发性无精、严重少精症与Y染色体无精子因子(AZF)微缺失之间的关系.方法:采用多重聚合酶链反应技术对103例原发无精子症、72例原发严重少精症患者及60例正常生育男性进行AZFa、AZFb、AZFc 3个区域微缺失分析.结果:60例正常生育男性未发现Y染色体AZF区域微缺失,175例生精障碍患者中发现AZF微缺失19例,总缺失率为10.9%.其中11例无精症患者和4例少精症患者的缺失发生在AZFc区域,缺失率为8.6%;1例无精症患者和2例少精症患者发生AZFb、AZFc双重缺失,缺失率为1.7%;1例无精症患者发生AZFa、b、c 3个区域同时微缺失,缺失率0.6%.生精障碍组与正常生育男性组比较Y染色体AZF区域微缺失率差异有统计学意义(P<0.01).结论:Y染色体AZF区域微缺失是引起男性无精、少精子症的重要原因之一.采用多重聚合酶链反应技术对原发无精、少精子症患者在单精子注射(ICSI)之前进行微缺失筛查是必要的.