Whole exome sequencing in a multi-generation family from India reveals a genetic variation c.10C>T (p.Gln4Ter) in keratin 5 gene associated with Dowling–Degos disease

Abstract Background: Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. Little is known about susceptibility genes for GD in the three-generation family.Methods: DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. We utilize the Whole Exome Sequencing(WES) to screen and the Sanger sequencing confirmed potential disease-causing genes.Results:In this case study, there are five patients with Graves’ disease(GD) from a three-generation family. We firstly revealed the SNVs of MAP7D2(c. 452C>T: p. A151V), SLC1A7(c. 1204C>T: p. R402C), TRAF3IP3(c. 209A>T: p. N70I), PTPRB(c. 3472A>G: p. S1158G), PIK3R3(c. 121C>T: p. P41S), DISC1(c. 1591G>C: p. G531R) were associated with the familial GD. The Sanger sequencing confirmed these variations and more importantly is that the PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions.Conclusion: The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

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Next-generation sequencing refines the genetic architecture of Greek GnRH-deficient patients

Endocrine Connections ◽

10.1530/ec-19-0010 ◽

2019 ◽

Vol 8 (5) ◽

pp. 468-480 ◽

Cited By ~ 2

Author(s):

M I Stamou ◽

P Varnavas ◽

L Plummer ◽

V Koika ◽

N A Georgopoulos

Keyword(s):

Genetic Variation ◽

Next Generation Sequencing ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Wide Spectrum ◽

Next Generation ◽

Whole Exome ◽

Low Prevalence ◽

Generation Sequencing

Isolated gonadotropin-releasing hormone (GnRH) deficiency (IGD) is a rare disease with a wide spectrum of reproductive and non-reproductive clinical characteristics. Apart from the phenotypic heterogeneity, IGD is also highly genetically heterogeneous with >35 genes implicated in the disease. Despite this genetic heterogeneity, genetic enrichment in specific subpopulations has been described. We have previously described low prevalence of genetic variation in the Greek IGD cohort discovered with utilization of Sanger sequencing in 14 known IGD genes. Here, we describe the expansion of genetic screening in the largest IGD Greek cohort that has ever been studied with the usage of whole-exome sequencing, searching for rare sequencing variants (RSVs) in 37 known IGD genes. Even though Sanger sequencing detected genetic variation in 21/81 IGD patients in 7/14 IGD genes without any evidence of oligogenicity, whole exome sequencing (WES) revealed that 27/87 IGD patients carried a rare genetic change in a total of 15 genes with 4 IGD cases being oligogenic. Our findings suggest that next-generation sequencing (NGS) techniques can discover previously undetected variation, making them the standardized method for screening patients with rare and/or more common disorders.

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S39 Whole Exome Sequencing in Chronic Thromboembolic Pulmonary Hypertension Reveals Biologically Plausible Novel Genetic Variation

Thorax ◽

10.1136/thoraxjnl-2012-202678.045 ◽

2012 ◽

Vol 67 (Suppl 2) ◽

pp. A21-A21

Author(s):

C McCabe ◽

K Sheares ◽

S Graf ◽

J Pepke-Zaba ◽

N Morrell

Keyword(s):

Pulmonary Hypertension ◽

Genetic Variation ◽

Exome Sequencing ◽

Whole Exome Sequencing ◽

Chronic Thromboembolic Pulmonary Hypertension ◽

Whole Exome ◽

Thromboembolic Pulmonary Hypertension

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Screening of Graves' Disease Susceptibility Genes by Whole Exome Sequencing in a Three-generation Family

10.21203/rs.3.rs-137863/v1 ◽

2021 ◽

Author(s):

Zhuoqing Hu ◽

Wei Li ◽

Miaosheng Li ◽

Hao Wei ◽

Zhihui Hu ◽

...

Keyword(s):

Exome Sequencing ◽

Whole Exome Sequencing ◽

Sanger Sequencing ◽

Familial Aggregation ◽

Susceptibility Genes ◽

Graves Disease ◽

Chinese Han ◽

Whole Exome ◽

Generation Family ◽

Protein Functions

Abstract Background Graves’ disease(GD) has a tendency for familial aggregation, but it is uncommon to occur in more than two generations. However, little is known about susceptibility genes for GD in the three-generation family. Methods DNA were extracted from three-generation familial GD patient with a strong genetic background in a Chinese Han population. The Whole Exome Sequencing (WES) was utilized to screen the genome for SNVs associated with GD and the Sanger Sequencing was used to confirm the potential disease-causing genes. Results In the case study, there were five patients with Graves’ disease(GD) from a three-generation family. The SNVs of MAP7D2(c. 452C > T: p. A151V), SLC1A7(c. 1204C > T: p. R402C), TRAF3IP3(c. 209A > T: p. N70I), PTPRB(c. 3472A > G: p. S1158G), PIK3R3(c. 121C > T: p. P41S), DISC1(c. 1591G > C: p. G531R) were found to be associated with the familial GD and the Sanger sequencing had confirmed these variations. Furthermore, PolyPhen-2 score showed that the variants in TRAF3IP3, PTPRB, PIK3R3 are more likely to change protein functions. Conclusion The MAP7D2, SLC1A7, TRAF3IP3, PTPRB, PIK3R3, DISC1 may be the candidate susceptibility genes for familial GD from a three generations family.

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