A rare association of interrupted aortic arch type C and microdeletion 22q11.2

Microdeletion 22q11.2 is associated with a variety of findings, and the most common are cardiac defects. It is very frequently associated with interrupted aortic arch (IAA) type B and very rarely with type A and type C. Here we report the first case of IAA type C associated with 22q11.2 deletion in Serbia and, to the best of our knowledge, the fourth case described worldwide so far. By this report we would like to point out that all patients with IAA type C who have additional features specific for 22q11.2 microdeletion syndrome should be screened for the presence of this deletion.     

A further case of the recurrent 15q24 microdeletion syndrome,detected by array CGH

We report on a 10-year-old patient with developmental delay, craniofacial dysmorphism, digital and genital abnormalities. In addition, muscular hypotonia, strabism, and splenomegaly were observed; inguinal and umbilical hernias were surgically corrected. Mucopolysaccharidoses and CDG syndromes could not be found. Chromosome analysis revealed a normal male karyotype (46,XY). A more detailed investigation of the patient's genomic DNA by microarray-based comparative genomic hybridization (array CGH) detected an interstitial 3.7 Mb deletion ranging from 15q24.1 to 15q24.3 which was shown to be de novo. Interstitial deletions involving 15q24 are rare. Sharp et al. (Hum Mol Genet 16:567-572, 2007) recently characterized a recurrent 15q24 microdeletion syndrome with breakpoints in regions of segmental duplications. The de novo microdeletion described here colocalizes with the minimal deletion region of the 15q24 microdeletion syndrome. The distinct clinical phenotype associated with this novel microdeletion syndrome is similar to the phenotype of our patient with respect to specific facial features, developmental delay, microcephaly, digital abnormalities, and genital abnormalities in males. We present a genotype-phenotype correlation and comparison with patients from the literature.     

Monozygous twins with a microdeletion syndrome involving BTK, DDP1, and two other genes; evidence of intact dendritic cell development and TLR responses

We report for the first time monozygous twins with a microdeletion syndrome involving genes coding for Bruton’s tyrosine kinase (Btk) and deafness-dystonia peptide 1 (DDP1), and two other genes. Apart from its essential role in B cell development, Btk is indicated to affect signaling mediated by toll like receptors (TLRs) and development of dendritic cells (DCs) but results are conflictive. The twins revealed normal numbers of plasmacytoid and myeloid DCs (pDCs and mDCs). Moreover, BTK null cells from these patients exhibited robust responses to TLR agonists, normal natural killer (NK) cell activity, and normal pDC functions. Conclusion: Our results do not indicate the essential role of Btk in TLR signaling and DC development.     

习惯性流产与Y染色体微缺失关系的研究

目的:探讨Y染色体无精子因子(AZF)微缺失在习惯性流产夫妇中的发生情况。方法:采用聚合酶链反应技术对7例习惯性流产夫妇中的男性Y染色体上AZF基因(STS)上的3个位点SY157、SY254、SY255及ZFX/ZFY基因进行检测。结果:7例男性中的1例(14.29%)在所检测的3个位点有1处缺失,10例可生育且无流产史的男性未见任何微缺失。结论:习惯性流产夫妇中男性AZF缺失可能是造成习惯性流产的一个原因,两者有一定的相关性。     

PCR screening for 22q11.2 microdeletion: development of a new cost-effective diagnostic tool

BACKGROUND: Del22q11.2 syndrome is the most frequent known chromosomal microdeletion syndrome. Previous studies suggest that a substantial number of patients with congenital heart disease have a 22q11 deletion. The molecular diagnosis of Del22q11.2 is usually made by fluorescence in situ hybridization, an expensive and not widely available technique. We developed an efficient and cost-effective PCR SNP assay designed for the screening of 22q11.2 deletion through consecutive homozygosity. METHODS: Through the screening of dbSNP we have selected SNP markers located in the 22q11.2 microdeleted region. Population heterozygosities were determined in 213 normal individuals. Designed assays consisted of PCR amplification followed by restriction enzyme digestion. Fragments generated were visualized on agarose gel and genotyped. RESULTS: Selected markers were: rs5748411, rs2238778, rs4819523 and rs4680. All selected markers were localized in the 22q11.2 deleted region. Allele and genotype frequencies of all selected markers were under Hardy-Weinberg equilibrium. Selected SNPs were not in linkage disequilibrium. Predicted assay specificity was estimated to be 92.86% in the Brazilian population. CONCLUSIONS: The use of consecutive homozygosity in this SNP-based diagnostic test may be used as a cost-effective tool in reference molecular genetics laboratories.     

男性原发无(少)精子症Y染色体微缺失的筛查研究

目的:探讨男性原发无精子症和少精子症与Y染色体无精子症因子(AZF)微缺失的关系。方法:应用多重PCR技术对原发无精子症(24例)和少精子症(19例)患者基因组DNA进行Y染色体连锁的6个序列标签位点缺失分析。结果:43例患者中检出有Y染色体微缺失4例,缺失率为9.3%,其中无精子症3例,少精子症1例。结论:Y染色体微缺失是原发无精子症和少精子症的重要原因之一,对原发无精子症和少精子症患者进行Y染色体微缺失的常规筛查是有必要的。     

Chromosome 2p15-p16.1 microduplication in a boy with congenital anomalies: Is it a distinctive syndrome?

Array-based comparative genomic hybridization is a routine technology that helps clinicians in the diagnostic evaluation of individuals presenting with developmental delay or malformation anomalies. With this technique, several patients affected by microdeletion 2p15-p16.1 have been reported and this anomaly has been recognized as a distinct syndrome. In contrast, clinical features of patients with microduplication in the same region have been registered mainly in clinical and genetic data-bases and to date just a single patient has been reported in detail in the literature.A 12-year-old boy with 2p15-p16.1 microduplication presented with moderate neurodevelopment delay, epileptic seizures, behavioral disturbances, and minor dysmorphic features. The role of 2p15-p16.1 duplication in this case, and the others published in data-bases with a similar molecular duplication, are discussed.     

Immunological abnormalities in CHARGE syndrome

Immune deficiency can be part of CHARGE syndrome but often receives only limited attention. We present two patients with CHARGE syndrome confirmed CHD7 mutations who had severe T-cell deficiency, and review 15 CHARGE patients from the literature with immunological problems. Most of them had severe T-cell deficiency, although the spectrum also included mild T-cell deficiency and isolated humoral immune deficiency. We conclude that immunodeficiency can form an important symptom in CHARGE syndrome although the frequency and exact nature are still insufficiently known. We propose to evaluate immune functions in all CHARGE syndrome patients, to estimate the frequency and nature of the accompanying immunodeficiency, and to obtain better data regarding prognosis and management.