Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

Hakan Cangul; Zehra Aycan; Alvaro Olivera-Nappa; Halil Saglam; Nadia A Schoenmakers; Kristien Boelaert; Semra Cetinkaya; Omer Tarim; Ece Bober; Feyza Darendeliler; Veysel Bas; Korcan Demir; Banu K Aydin; Michaela Kendall; Trevor Cole; Wolfgang Högler; V Krishna K Chatterjee; Timothy G Barrett; Eamonn R Maher

doi:10.1111/cen.12127

Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

Hakan Cangul, Zehra Aycan, Alvaro Olivera-Nappa, Halil Saglam, Nadia A Schoenmakers, Kristien Boelaert, Semra Cetinkaya, Omer Tarim, Ece Bober, Feyza Darendeliler, Veysel Bas, Korcan Demir, Banu K Aydin, Michaela Kendall, Trevor Cole, Wolfgang Högler, V Krishna K Chatterjee, Timothy G Barrett, Eamonn R Maher

Research output: Contribution to journal › Article › peer-review

39 Citations (Scopus)

Abstract

OBJECTIVE: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).

CONTEXT: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.

DESIGN: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families.

PATIENTS: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families.

MEASUREMENTS: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.

RESULTS: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).

CONCLUSIONS: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.

Original language	English
Pages (from-to)	275-81
Number of pages	7
Journal	Clinical Endocrinology
Volume	79
Issue number	2
DOIs	https://doi.org/10.1111/cen.12127
Publication status	Published - Aug 2013

Keywords

Adolescent
Adult
Child
Child, Preschool
Congenital Hypothyroidism
Consanguinity
Female
Humans
Infant
Infant, Newborn
Iodide Peroxidase
Male
Mutation, Missense
Pakistan
Thyroid Hormones
Turkey
Journal Article
Research Support, Non-U.S. Gov't

Access to Document

10.1111/cen.12127

Cite this

Cangul, H., Aycan, Z., Olivera-Nappa, A., Saglam, H., Schoenmakers, N. A., Boelaert, K., Cetinkaya, S., Tarim, O., Bober, E., Darendeliler, F., Bas, V., Demir, K., Aydin, B. K., Kendall, M., Cole, T., Högler, W., Chatterjee, V. K. K., Barrett, T. G., & Maher, E. R. (2013). Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community. Clinical Endocrinology, 79(2), 275-81. https://doi.org/10.1111/cen.12127

@article{49bdb6c6c5f64792afd3c42951877ff1,

title = "Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community",

abstract = "OBJECTIVE: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).CONTEXT: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.DESIGN: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families.PATIENTS: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families.MEASUREMENTS: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.RESULTS: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).CONCLUSIONS: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.",

keywords = "Adolescent, Adult, Child, Child, Preschool, Congenital Hypothyroidism, Consanguinity, Female, Humans, Infant, Infant, Newborn, Iodide Peroxidase, Male, Mutation, Missense, Pakistan, Thyroid Hormones, Turkey, Journal Article, Research Support, Non-U.S. Gov't",

author = "Hakan Cangul and Zehra Aycan and Alvaro Olivera-Nappa and Halil Saglam and Schoenmakers, {Nadia A} and Kristien Boelaert and Semra Cetinkaya and Omer Tarim and Ece Bober and Feyza Darendeliler and Veysel Bas and Korcan Demir and Aydin, {Banu K} and Michaela Kendall and Trevor Cole and Wolfgang H{\"o}gler and Chatterjee, {V Krishna K} and Barrett, {Timothy G} and Maher, {Eamonn R}",

note = "{\textcopyright} 2012 John Wiley & Sons Ltd.",

year = "2013",

month = aug,

doi = "10.1111/cen.12127",

language = "English",

volume = "79",

pages = "275--81",

journal = "Clinical Endocrinology",

issn = "0300-0664",

publisher = "Wiley",

number = "2",

}

Cangul, H, Aycan, Z, Olivera-Nappa, A, Saglam, H, Schoenmakers, NA, Boelaert, K, Cetinkaya, S, Tarim, O, Bober, E, Darendeliler, F, Bas, V, Demir, K, Aydin, BK, Kendall, M, Cole, T, Högler, W, Chatterjee, VKK, Barrett, TG & Maher, ER 2013, 'Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community', Clinical Endocrinology, vol. 79, no. 2, pp. 275-81. https://doi.org/10.1111/cen.12127

TY - JOUR

T1 - Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

AU - Cangul, Hakan

AU - Aycan, Zehra

AU - Olivera-Nappa, Alvaro

AU - Saglam, Halil

AU - Schoenmakers, Nadia A

AU - Boelaert, Kristien

AU - Cetinkaya, Semra

AU - Tarim, Omer

AU - Bober, Ece

AU - Darendeliler, Feyza

AU - Bas, Veysel

AU - Demir, Korcan

AU - Aydin, Banu K

AU - Kendall, Michaela

AU - Cole, Trevor

AU - Högler, Wolfgang

AU - Chatterjee, V Krishna K

AU - Barrett, Timothy G

AU - Maher, Eamonn R

PY - 2013/8

Y1 - 2013/8

N2 - OBJECTIVE: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).CONTEXT: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.DESIGN: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families.PATIENTS: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families.MEASUREMENTS: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.RESULTS: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).CONCLUSIONS: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.

AB - OBJECTIVE: In this study, we aimed to investigate the genetic background of thyroid dyshormonogenesis (TDH).CONTEXT: Thyroid dyshormonogenesis comprises 10-15% of all cases of congenital hypothyroidism (CH), which is the most common neonatal endocrine disorder, and might result from disruptions at any stage of thyroid hormone biosynthesis. Currently seven genes (NIS, TPO, PDS, TG, IYD, DUOX2 and DUOXA2) have been implicated in the aetiology of the disease.DESIGN: As TDH is mostly inherited in an autosomal recessive manner, we planned to conduct the study in consanguineous/multi-case families.PATIENTS: One hundred and four patients with congenital TDH all coming from consanguineous and/or multi-case families.MEASUREMENTS: Initially, we performed potential linkage analysis of cases to all seven causative-TDH loci as well as direct sequencing of the TPO gene in cases we could not exclude linkage to this locus. In addition, in silico analyses of novel missense mutations were carried out.RESULTS: TPO had the highest potential for linkage and we identified 21 TPO mutations in 28 TDH cases showing potential linkage to this locus. Four of 10 distinct TPO mutations detected in this study were novel (A5T, Y55X, E596X, D633N).CONCLUSIONS: This study underlines the importance of molecular genetic studies in diagnosis, classification and prognosis of CH and proposes a comprehensive mutation screening by new sequencing technology in all newly diagnosed primary CH cases.

KW - Adolescent

KW - Adult

KW - Child

KW - Child, Preschool

KW - Congenital Hypothyroidism

KW - Consanguinity

KW - Female

KW - Humans

KW - Infant

KW - Infant, Newborn

KW - Iodide Peroxidase

KW - Male

KW - Mutation, Missense

KW - Pakistan

KW - Thyroid Hormones

KW - Turkey

KW - Journal Article

KW - Research Support, Non-U.S. Gov't

U2 - 10.1111/cen.12127

DO - 10.1111/cen.12127

M3 - Article

C2 - 23236987

SN - 0300-0664

VL - 79

SP - 275

EP - 281

JO - Clinical Endocrinology

JF - Clinical Endocrinology

IS - 2

ER -

Thyroid dyshormonogenesis is mainly caused by TPO mutations in consanguineous community

Abstract

Keywords

Access to Document

Fingerprint

Cite this