Genetic and Developmental Disorders: Genetic Disorders |

Whole-Exome Sequencing Identifies a Novel Mutation of DNAI1 in Primary Ciliary Dyskinesia From a Chinese Family FREE TO VIEW

Ting Guo, PhD; Hong Luo, MD
Author and Funding Information

The Second Xiangya Hospital of Central South University, Changsha, China

Copyright 2016, American College of Chest Physicians. All Rights Reserved.

Chest. 2016;149(4_S):A248. doi:10.1016/j.chest.2016.02.258
Text Size: A A A
Published online

SESSION TITLE: Genetic Disorders

SESSION TYPE: Original Investigation Poster

PRESENTED ON: Saturday, April 16, 2016 at 11:45 AM - 12:45 PM

PURPOSE: To identify the causal gene in a PCD patient, whose parents are consanguineous marriage

METHODS: (1) According to medical history and auxiliary examination, a patient with Primary ciliary dyskinesia was identified in a consanguinity family. (2) The peripheral blood of 2 members was collected to extract DNA, including the PCD patient and her healthy son. Then DNA of the 2 members was analyzed by Whole-exome sequencing. (3) SNPs in sequencing data were excluded by the search of TGP database, YH database, ESP database and dbSNP database. (4) The variants carried by the PCD patient and not included in nomal member were selected after SNPs exclusion. (5) According to the characteristic of consanguineous marriage, homozygous mutants were the meaningful mutants and heterozygous mutants were deleted. (6) The selected variants were predicted by three online softwares:SIFT, Mutation Taster and Polyphen-2 to select deleterious variants. (7) The causal mutation was validated again by sanger sequencing. (8) The mutation identified in this article was searched in pubmed, Google scholar and HGMD database. (9) domain analysis, conservation analysis and protein structure prediction were performed.

RESULTS: After Whole-exome sequencing and various aspects of data analysis, a single homozygous missense mutation, c.1562T>G transition (p. I521S), was identified in DNAI1. This homozygous variant was not reported before.

CONCLUSIONS: (1) The novel homozygous variant c. 1562T>G (p. I521S) in DNAI1 (known causal gene) is the causal mutation for this PCD patient. The identification helps the patient to make a genetics diagnoses. (2) It contributes to the growing number of candidate mutational sites associated with PCD and benefits the future genetic counseling for PCD. (3) Exome capture sequencing is a necessary choice in genetic research of midget consanguinity family.

CLINICAL IMPLICATIONS: The novel homozygous variant c. 1562T>G of DNAI1 is implicated as the disease-causing gene in this Chinese consanguinity family. It expands the spectrum of DNAI1 mutations and benefits the future genetic counseling for PCD. Moreover, the identification of this novel mutation in DNAI1 indirectly indicates that exome capture and sequencing are beneficial for the genetic research of midget consanguinity families

DISCLOSURE: The following authors have nothing to disclose: Ting Guo, Hong Luo

No Product/Research Disclosure Information




Citing articles are presented as examples only. In non-demo SCM6 implementation, integration with CrossRef’s "Cited By" API will populate this tab (http://www.crossref.org/citedby.html).

Some tools below are only available to our subscribers or users with an online account.

Related Content

Customize your page view by dragging & repositioning the boxes below.

Find Similar Articles
CHEST Journal Articles
PubMed Articles
  • CHEST Journal
    Print ISSN: 0012-3692
    Online ISSN: 1931-3543