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317051

Use of Allele-Specific-Amplification Refractory Mutation System–Polymerase Chain Reaction for the Detection of Thyroid-Stimulating Hormone Receptor Gene Mutation in an Indian Fam

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Last updated: 24 Dec 2024

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Neonatal Screening

Abstract

The frequency of thyroid-stimulating hormone receptor (TSHR) gene variant c.1349G>T, p.arginine[R]450leucine[L] in the Asian population has been reported to be high. However, the whole exome sequencing (WES) performed using our samples could not detect this mutation. Moreover, the clinical utility of allele-specific (AS)-amplification refractory mutation system (ARMS)–polymerase chain reaction (PCR) has not been explored in the detection of TSHR gene mutation c.1349G>T, p.R450L in cases with thyroid dyshormonogenesis (TDH). Therefore, we aim to investigate the inheritance and TSHR gene mutation c.1349G>T, p.R450L in an Indian child with TDH and his biological parents. At present, the mutation analysis of TDH-causing genes like dual oxidase (DUOX2) [c.3200C>T, p.Ser(S)1067L] and thyroid peroxidase (TPO) [c.404C>A, p.Pro(P)135His(H)] by WES and TSHR gene variant c.1349G>T/p.R450L by AS-ARMS-PCR was performed. Three years and 1 month-old male child born to nonconsanguineous parents presented with constipation and prolonged indirect hyperbilirubinemia at 1.5 months of age. The evaluation revealed a very high level of serum thyroid stimulating hormone and a low level of free thyroxine (fT4) and fT3. The technetium99 scan showed increased tracer uptake in the thyroid gland. Out of 131 variants identified in TDH-causing genes by WES, DUOX2 gene variant c.3200C>T, p.S1067L and TPO gene variant c.404C>A, p.P135H were noticed to be clinically associated with TDH. Applying AS-ARMS-PCR for the first time, we report the whole Indian family carrying an autosomal heterozygous variant (c.1349G>T/p.R450L) in the hotspot mutation region of the TSHR gene. In conclusion, the known TSHR gene variant c.1349G>T/p.R450L (an autosomal heterozygous), and other variants of the DUOX2 gene (c.3200C>T, p.S1067L) and TPO gene (c.404C>A, p.P135H) might contribute to clinically more severe TDH in children born to carrier parents. We recommend a large-scale study and confirmation of the mutations by Sanger sequencing.

DOI

10.21608/anj.2023.227626.1072

Keywords

Gene mutations, TSH receptor (TSHR) gene, whole exome sequencing, AS-ARMS-PCR, Thyroid dyshormonogenesis

Authors

First Name

Venkanna

Last Name

Bhanothu

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

banothu.venkanna@gmail.com

City

Mumbai

Orcid

-

First Name

Simeone

Last Name

Fernandes

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

-

City

-

Orcid

-

First Name

Sudha

Last Name

Rao

MiddleName

Chandrashekhar

Affiliation

Pediatric Endocrinology & Neonatology, Bai Jerbai Wadia Hospital for Children, Acharya Dhonde Marg, Parel, Mumbai-12

Email

-

City

-

Orcid

-

First Name

Rachna

Last Name

Keshwani

MiddleName

-

Affiliation

Pediatric Endocrinology & Neonatology, Bai Jerbai Wadia Hospital for Children, Acharya Dhonde Marg, Parel, Mumbai-12

Email

-

City

-

Orcid

-

First Name

Shagun

Last Name

Shagun

MiddleName

W

Affiliation

Pediatric Endocrinology & Neonatology, Bai Jerbai Wadia Hospital for Children, Acharya Dhonde Marg, Parel, Mumbai-12

Email

-

City

-

Orcid

-

First Name

Suchitra

Last Name

Surve

MiddleName

-

Affiliation

Department of Clinical Research, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India.

Email

-

City

-

Orcid

-

First Name

Shailesh

Last Name

Pande

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

-

City

-

Orcid

-

First Name

Sudhakar

Last Name

DVS

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

-

City

-

Orcid

-

First Name

Neha

Last Name

Minde

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

-

City

-

Orcid

-

First Name

Shivamkumar

Last Name

Sriwas

MiddleName

-

Affiliation

Genetic Research Centre, ICMR-National Institute for Research in Reproductive and Child Health, Jehangir Merwanji Street, Parel, Mumbai 400012, India

Email

-

City

-

Orcid

-

Volume

6

Article Issue

1

Related Issue

45671

Issue Date

2024-01-01

Receive Date

2023-08-07

Publish Date

2024-01-01

Page Start

7

Page End

36

Online ISSN

2636-3569

Article File

ANJ_Volume 6_Issue 1_Pages 7-36.pdf

PDF . 1.2MB

Link

https://anj.journals.ekb.eg/article_317051.html

Detail API

https://anj.journals.ekb.eg/service?article_code=317051

Order

2

Type

Original Article

Type Code

959

Publication Type

Journal

Publication Title

Annals of Neonatology

Publication Link

https://anj.journals.ekb.eg/

MainTitle

Use of Allele-Specific-Amplification Refractory Mutation System–Polymerase Chain Reaction for the Detection of Thyroid-Stimulating Hormone Receptor Gene Mutation in an Indian Family with Thyroid Dyshormonogenesis

Details

Type

Article

Created At

24 Dec 2024