Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report

VACTERL association is a rare genetic disorder involving at least three of the following congenital malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until...

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Main Authors:	Siti Aishah Sulaiman, Nor Azian Abdul Murad, Chow, Yock Ping, Zam Zureena Mohd Rani, Salwati Shuib, Dayang Anita A. Aziz, Hana Azhari, Sharifah Azween Syed Omar, Zarina Abdul Latiff, Rahman Jamal
Format:	Article
Language:	English
Published:	Pusat Perubatan Universiti Kebangsaan Malaysia 2018
Online Access:	http://journalarticle.ukm.my/13247/ http://journalarticle.ukm.my/13247/ http://journalarticle.ukm.my/13247/1/39-153-1-PB.pdf

id	ukm-13247
recordtype	eprints
spelling	ukm-132472019-08-02T04:31:14Z http://journalarticle.ukm.my/13247/ Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report Siti Aishah Sulaiman, Nor Azian Abdul Murad, Chow, Yock Ping Zam Zureena Mohd Rani, Salwati Shuib, Dayang Anita A. Aziz, Hana Azhari, Sharifah Azween Syed Omar, Zarina Abdul Latiff, Rahman Jamal, VACTERL association is a rare genetic disorder involving at least three of the following congenital malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until now, the aetiology of VACTERL association is unknown, particularly at the molecular level. Here, we performed whole exome sequencing (WES) of an infant with VACTERL association. The patient was delivered prematurely at 30 weeks and had 4/6 of the VACTERL malformations. Trio-WES analysis was performed using Torrent Suite and ANNOVAR. Polymorphisms with an allele frequency of >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, X-linked and di-genic inheritance traits. In this patient, no homozygous, compound heterozygous or X-linked mutations was associated with VACTERL. However, we identified two heterozygous mutations; KIF27 (ENST00000297814: c.3004A> C:p.N1002H) and GNAS (ENST00000371098: c.205C>A:p.H69N) genes that were inherited from her father and mother respectively. A de novo, IFT140 gene mutation (ENST00000426508: c.683C>G:p.S228C) was also identified in this patient. The VACTERL phenotype in this patient may due to heterozygous mutations affecting KIF27 and GNAS genes, inherited via autosomal recessive trait. In addition, the IFT140 gene mutation may also be involved. These genes are known to be directly or non-directly involved in the sonic hedgehog signalling that is known to be implicated in VACTERL. This is the first report of these genetic mutations in association with VACTERL. Pusat Perubatan Universiti Kebangsaan Malaysia 2018 Article PeerReviewed application/pdf en http://journalarticle.ukm.my/13247/1/39-153-1-PB.pdf Siti Aishah Sulaiman, and Nor Azian Abdul Murad, and Chow, Yock Ping and Zam Zureena Mohd Rani, and Salwati Shuib, and Dayang Anita A. Aziz, and Hana Azhari, and Sharifah Azween Syed Omar, and Zarina Abdul Latiff, and Rahman Jamal, (2018) Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report. Asia-Pacific Journal of Molecular Medicine, 8 (2). pp. 1-10. ISSN 2232-0326 http://spaj.ukm.my/apjmm/index.php/apjmm/issue/view/19
repository_type	Digital Repository
institution_category	Local University
institution	Universiti Kebangasaan Malaysia
building	UKM Institutional Repository
collection	Online Access
language	English
description	VACTERL association is a rare genetic disorder involving at least three of the following congenital malformations: vertebral defects (V), anal atresia (A), cardiac defects (C), trachea-oesophageal fistula with or without oesophageal atresia (TE), renal anomalies (R) and limb abnormalities (L). Until now, the aetiology of VACTERL association is unknown, particularly at the molecular level. Here, we performed whole exome sequencing (WES) of an infant with VACTERL association. The patient was delivered prematurely at 30 weeks and had 4/6 of the VACTERL malformations. Trio-WES analysis was performed using Torrent Suite and ANNOVAR. Polymorphisms with an allele frequency of >0.01 were excluded, and the remaining variants were filtered based on de novo mutations, autosomal recessive, X-linked and di-genic inheritance traits. In this patient, no homozygous, compound heterozygous or X-linked mutations was associated with VACTERL. However, we identified two heterozygous mutations; KIF27 (ENST00000297814: c.3004A> C:p.N1002H) and GNAS (ENST00000371098: c.205C>A:p.H69N) genes that were inherited from her father and mother respectively. A de novo, IFT140 gene mutation (ENST00000426508: c.683C>G:p.S228C) was also identified in this patient. The VACTERL phenotype in this patient may due to heterozygous mutations affecting KIF27 and GNAS genes, inherited via autosomal recessive trait. In addition, the IFT140 gene mutation may also be involved. These genes are known to be directly or non-directly involved in the sonic hedgehog signalling that is known to be implicated in VACTERL. This is the first report of these genetic mutations in association with VACTERL.
format	Article
author	Siti Aishah Sulaiman, Nor Azian Abdul Murad, Chow, Yock Ping Zam Zureena Mohd Rani, Salwati Shuib, Dayang Anita A. Aziz, Hana Azhari, Sharifah Azween Syed Omar, Zarina Abdul Latiff, Rahman Jamal,
spellingShingle	Siti Aishah Sulaiman, Nor Azian Abdul Murad, Chow, Yock Ping Zam Zureena Mohd Rani, Salwati Shuib, Dayang Anita A. Aziz, Hana Azhari, Sharifah Azween Syed Omar, Zarina Abdul Latiff, Rahman Jamal, Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
author_facet	Siti Aishah Sulaiman, Nor Azian Abdul Murad, Chow, Yock Ping Zam Zureena Mohd Rani, Salwati Shuib, Dayang Anita A. Aziz, Hana Azhari, Sharifah Azween Syed Omar, Zarina Abdul Latiff, Rahman Jamal,
author_sort	Siti Aishah Sulaiman,
title	Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
title_short	Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
title_full	Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
title_fullStr	Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
title_full_unstemmed	Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report
title_sort	mutations in kif27, gnas and ift140 genes in a patient with vacterl association: a case report
publisher	Pusat Perubatan Universiti Kebangsaan Malaysia
publishDate	2018
url	http://journalarticle.ukm.my/13247/ http://journalarticle.ukm.my/13247/ http://journalarticle.ukm.my/13247/1/39-153-1-PB.pdf
first_indexed	2023-09-18T20:04:26Z
last_indexed	2023-09-18T20:04:26Z
_version_	1777407063293427712

Mutations in KIF27, GNAS and IFT140 genes in a patient with VACTERL association: a case report

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