During the period 1 January 1990-31 December 1990, 68 neonates with congenital abnormalities were successfully analysed for chromosome abnormalities in order to determine the contribution of chromosome aberrations to the aetiology of congenital abnormalities. The neonates were karyotyped employing the G-banding technique. Twenty-nine babies showed abnormal chromosome karyotypes. Twenty-six were observed to have classic trisomy syndromes; ie. trisomy 21 (32.3%), trisomy 18 (3.0%), and trisomy 13 (3.0%). The mean maternal age of the mothers with babies having normal karyotype was lower than the mean maternal age of the mothers having babies with abnormal karyotypes. From this study the incidence of congenital abnormalities due to chromosomal abnormalities is found to be 1:838 livebirths. Frequency of newborns having abnormal chromosomes is 0.14% for Malays, 0.12% for Chinese and 0.06% for Indians.
Prenatal diagnosis is a rapidly evolving speciality. Screening for aneuploidy begins with non-sonographic features of background risk of maternal age and past and family history. It is possible to diagnose major structural defects in the foetus using second trimester scans. Serum biochemistry markers in the early second trimester were added to increase the detection rate of aneuploidy. However, as some of these abnormalities were amenable to detection earlier in the first trimester, newer modalities were introduced. Nuchal translucency (NT) measurement was one of the main advances with regard to first trimester screening. Additional markers such as the presence of nasal bone, tricuspid regurgitation, ductus venosus and megacystis; together with first trimester serum biochemistry, further enhanced the detection rate of chromosomal abnormalities. Advances in research and technology have resulted in the availability of non-invasive prenatal testing from 10 weeks of gestation. This has facilitated the detection of the three major chromosomal aneuploidies at very early gestation. However, there are a wide range of genetic syndromes that are not confined to the main trisomies. There are specific markers on ultrasound that can be linked to specific syndromes. Hence, a structured and stepwise approach is needed to identify and reach a possible diagnosis. As anomalies are classified into malformations, deformations and disruptions, it is important to note that not all markers detected are due to genetic syndromes and not all genetic syndromes can be detected on ultrasound scan. In this chapter, we outline common structural markers and their association with main genetic syndromes.
Developmental delay and/or intellectual disability (DD/ID) affects 1-3% of all children. At least half of these are thought to have a genetic etiology. Recent studies have shown that massively parallel sequencing (MPS) using a targeted gene panel is particularly suited for diagnostic testing for genetically heterogeneous conditions. We report on our experiences with using massively parallel sequencing of a targeted gene panel of 355 genes for investigating the genetic etiology of eight patients with a wide range of phenotypes including DD/ID, congenital anomalies and/or autism spectrum disorder. Targeted sequence enrichment was performed using the Agilent SureSelect Target Enrichment Kit and sequenced on the Illumina HiSeq2000 using paired-end reads. For all eight patients, 81-84% of the targeted regions achieved read depths of at least 20×, with average read depths overlapping targets ranging from 322× to 798×. Causative variants were successfully identified in two of the eight patients: a nonsense mutation in the ATRX gene and a canonical splice site mutation in the L1CAM gene. In a third patient, a canonical splice site variant in the USP9X gene could likely explain all or some of her clinical phenotypes. These results confirm the value of targeted MPS for investigating DD/ID in children for diagnostic purposes. However, targeted gene MPS was less likely to provide a genetic diagnosis for children whose phenotype includes autism.
The FOXE1 gene was screened for mutations in a cohort of 34 unrelated patients with congenital hypothyroidism, 14 of whom had thyroid dysgenesis and 18 were normal (the thyroid status for 2 patients was unknown). The entire coding region of the FOXE1 gene was PCR-amplified, then analyzed using single-stranded conformational polymorphism, followed by confirmation by direct DNA sequencing. DNA sequencing analysis revealed a heterozygous A>G transition at nucleotide position 394 in one of the patients. The nucleotide transition changed asparagine to aspartate at codon 132 in the highly conserved region of the forkhead DNA binding domain of the FOXE1 gene. This mutation was not detected in a total of 104 normal healthy individuals screened. The binding ability of the mutant FOXE1 protein to the human thyroperoxidase (TPO) promoter was slightly reduced compared with the wild-type FOXE1. The mutation also caused a 5% loss of TPO transcriptional activity.
This study was aimed to see the difference between chondrocytes from normal cartilage compared to chondrocytes from microtic cartilage. Specific attentions were to characterize the growth of chondrocytes in terms of cell morphology, growth profile and RT-PCR analysis.