Two large novel alpha-globin gene cluster deletions causing alpha(0)-thalassemia in two Chinese families.

INTRODUCTION: Monosomy of terminal 16p13.3 is a relatively common subtelomeric abnormality, most affected individuals presented α-thalassemia, some also have mental retardation, developmental abnormalities and/or speech delay and facial dysmorphism, which is termed ATR-16 syndrome. Here, we reported two novel 16p13.3 deletions involving the α-globin gene cluster and multispecies conserved sequences (MCSs), causing only a phenotype of α-thalassemia. METHODS: Samples were collected from members of the two families and were subjected to haematological and comprehensive genetic analysis. RESULTS: The novel 108 Kb deletion in family A extends from the non-protein coding RNA gene (WASIR2) to the NPRL3 gene, removing MCS-R1 to R3. This deletion should arise de novo because it wasn't detected in both parents. The novel 336 Kb deletion in family B should extend from telomere to âˆ¼ chr16:336000, removing the entire α-globin gene cluster. Carriers of these two deletions presented with microcytosis and hypochromic red cells, in accordance with a phenotype of α0-thalassemia carrier. CONCLUSION: Our study increases the mutation spectrum of α-thalassemia. MCSs deletion should be considered in clinical practice of thalassemia screening and diagnosis.

Application of noninvasive fetal trisomy testing based on massively parallel sequencing for the detection of chromosomal deletions and duplications / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the value of noninvasive fetal trisomy testing based on massively parallel sequencing for the detection of chromosomal deletions and duplications.</p><p><b>METHODS</b>Peripheral venous blood was taken from pregnant women with a high risk. Free fetal DNA in maternal plasma was used for library construction and subjected to massively parallel sequencing. Positive results were validated by traditional karyotype analysis or array-CGH. Phenotype of the fetus was observed through patholoical evaluation.</p><p><b>RESULTS</b>Thirteen out of 629 cases were suspected to harbor chromosomal aberrations, which included 9 aneuploid cases and 4 structural abnormalities. The latter included one case with dup (18q) (14.35 Mb), del (18q) (21.34 Mb), one with dup (3q) (35 Mb) and two with dup (7q) (7.0 Mb). Among these, dup (18q ) (14.35 Mb), del (18q) (21.34 Mb) and dup (3q) (35 Mb) were confirmed by karyotype analysis and patholoical evaluation. However, the two cases with dup (7q) were validated by karyotype analysis and array-CGH as false positives. The phenotype with the fetus also presented as normal.</p><p><b>CONCLUSION</b>The introduction of maternal plasma sequencing for prenatal testing could dramatically improve the efficiency for detecting large, partial (> 10 Mb) chromosomal deletions and duplications.</p>