Targeted Next Generation Sequencing Reveals a Novel Intragenic Deletion of the TPO Gene in a Family with Intellectual Disability

详细信息    查看全文

• 作者：Zafar Iqbal ; Kornelia Neveling ; Attia Razzaq ; Mohsin Shahzad ; Muhammad Yasir Zahoor ; Muhammad Qasim ; Christian Gilissen ; Nienke Wieskamp ; Michael P. Kwint ; Sabine Gijsen ; Arjan P.M. de Brouwer ; Joris A. Veltman ; Sheikh Riazuddin ; Hans van Bokhoven
• 关键词：Next generation sequencing ; Intellectual disability ; Homozygosity mapping ; Submicroscopic ; TPO ; Congenital hypothyroidism
• 刊名：Archives of Medical Research
• 出版年：2012
• 出版时间：May, 2012
• 年：2012
• 卷：43
• 期：4
• 页码：312-316
• 全文大小：327 K

文摘

| Figures/TablesFigures/Tables | ReferencesReferences

Backgrounds and Aims

Next generation sequencing (NGS) approaches have revolutionized the identification of mutations underlying genetic disorders. This technology is particularly useful for the identification of mutations in known and new genes for conditions with extensive genetic heterogeneity. In the present study we investigated a consanguineous Pakistani family with intellectual disability (ID).

Methods

Genotyping was carried out using 250k and 6k SNP microarrays in order to perform homozygosity mapping and copy number variation (CNV) analysis. Targeted NGS was performed to identify the genetic defect in this family. qPCR was performed to validate and confirm the NGS result.

Results

Homozygosity mapping positioned the causative defect on chromosome 2p25.3-p25.2. Subsequent targeted NGS revealed an intragenic deletion of five exons of the gene TPO.

Conclusions

NGS is a powerful method to uncover submicroscopic structural variations. This result demonstrates that an unbiased screening approach such as NGS can help to?identify even unexpected disease-causing mutations.