Association of X Chromosome Aberrations with Male Infertility

Male infertility is caused by spermatogenetic failure, clinically noted as oligoor azoospermia. Approximately 20% of infertile patients carry a genetic defect. The most frequent genetic defect leading to azoospermia (or severe oligozoospermia) is Klinefelter syndrome (47, XXY), which is numerical chromosomal abnormality and Y- structural chromosome aberration. The human X chromosome is the most stable of all human chromosomes. The X chromosome is loaded with regions of acquired, rapidly evolving genes. The X chromosome may actually play an essential role in male infertility and sperm production. Here we will describe X chromosome aberrations, which are associated with male infertility.

Analysis of Genomic Copy Number Variation in Miscarriages During Early and Middle Pregnancy

The purpose of this study was to explore the copy number variations (CNVs) associated with miscarriage during early and middle pregnancy and provide useful genetic guidance for pregnancy and prenatal diagnosis. A total of 505 fetal specimens were collected and CNV sequencing (CNV-seq) analysis was performed to determine the types and clinical significance of CNVs, and relevant medical records were collected. The chromosomal abnormality rate was 54.3% (274/505), among which the numerical chromosomal abnormality rate was 40.0% (202/505) and structural chromosomal abnormality rate was 14.3% (72/505). Chromosomal monosomy mainly occurred on sex chromosomes, and chromosomal trisomy mainly occurred on chromosomes 16, 22, 21, 15, 13, and 9. The incidence of numerical chromosomal abnormalities in ≥35 year-old age pregnant women was significantly higher than <35 year-old age group. The highest incidence of pathogenic CNV (pCNV) was found in fetuses at ≤6 weeks of pregnancy (5.26%), and the incidence of variants of unknown significance (VOUS) CNVs decreased gradually with the increase of gestational age. The rate of chromosomal abnormalities of fetuses in early pregnancy (59.5%) was higher than that of fetuses in middle pregnancy (27.2%) (p < 0.001). There were 168 genes in VOUS + pCNV regions. 41 functions and 12 pathways (p < 0.05) were enriched of these genes by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis. Some meaningful genetic etiology information such as genes and pathways has been obtained, it may provide useful genetic guidance for pregnancy and prenatal diagnosis.

Clinical and cytogenetic profiles of children with autism in Kuantan Pahang

Introduction: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorder. The aetiology is not known in 75 to 80 percent of patients while in 20 to 25 percent a genetic cause is identified. There are very few studies on cytogenetic profile of ASD being carried out locally. This cross-sectional study was conducted to examine the clinical and cytogenetic profiles of paediatric ASD patients attending the Kuantan branch, National Autistic Society of Malaysia School. Methods: All paediatric patients (up to 18 years of age) attending the school in the year 2009/2010 were recruited. Clinical data was obtained by interviewing the guardians and assessment of the patients. Peripheral blood samples were collected for cytogenetic analysis. Results: Guardians of 14 out of 24 patients (58.3%) agreed for their children to be enrolled into the study. The age range was 5 to 12 years of age. The diagnostic subgroups were autistic disorder (13/14 patients) and Asperger syndrome (1/14). Approximately 80% had learning disability and history of allergy. Five patients had hyperactivity and none had history of seizures. There were family histories of developmental delay, mental retardation, epilepsy, psychiatric disorders and allergy. No structural or numerical chromosomal abnormality was detected. Conclusions: Although no cytogenetic abnormalities were identified, most probably due to the small sample size, it is crucial that genetic studies, including molecular genetic be explored as they would provide useful clinical insights and enhance understanding of the pathogenesis.

Cytogenetic and Clinical Assessment of a Family with Treacher Collins Syndrome

Treacher Collins syndrome (TCS) is a rare autosomal dominant disorder characterized by craniofacial deformities. It is the most common type of mandibulofacial dysostosis (MFD). The objective of this study is to do cytogenetic analysis of a TCS family. Physical examination and all available medical records were reviewed. 50 GTG-banded metaphases were analysed to detect any structural or numerical chromosomal abnormality. Downward slanting of palpebral fissures, hypoplasia of zygomatic arch complex, and hypoplasia of mandible were present in all. Cytogenetic findings show interstitial deletion in chromosomes 5(q32-q33) and 3(q23–q25). We report four members of three generations of a family having TCS in a unique way that the deletion has been found in 3q and 5q which has not been reported. Mosaicism of deletion on 5q was detected in all affected members whereas 3q deletion was found only in one member (II.2). This finding may represent a more severe manifestation of the TCS. Thus the evaluation and counselling of the TCS patients should be undertaken with caution.