TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis

Research output: Contribution to journalArticlepeer-review

Standard

TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis. / Cangul, Hakan; Aycan, Zehra; Saglam, Halil; Forman, Julia R; Cetinkaya, Semra; Tarim, Omer; Bober, Ece; Cesur, Yasar; Kurtoglu, Selim; Darendeliler, Feyza; Bas, Veysel; Eren, Erdal; Demir, Korcan; Kiraz, Aslihan; Aydin, Banu K; Karthikeyan, Ambika; Kendall, Michaela; Boelaert, Kristien; Shaw, Nick J; Kirk, Jeremy; Hogler, Wolfgang; Barrett, Timothy G; Maher, Eamonn R.

In: Journal of pediatric endocrinology & metabolism, Vol. 25, No. 5-6, 06.2012, p. 419-426.

Research output: Contribution to journalArticlepeer-review

Harvard

Cangul, H, Aycan, Z, Saglam, H, Forman, JR, Cetinkaya, S, Tarim, O, Bober, E, Cesur, Y, Kurtoglu, S, Darendeliler, F, Bas, V, Eren, E, Demir, K, Kiraz, A, Aydin, BK, Karthikeyan, A, Kendall, M, Boelaert, K, Shaw, NJ, Kirk, J, Hogler, W, Barrett, TG & Maher, ER 2012, 'TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis', Journal of pediatric endocrinology & metabolism, vol. 25, no. 5-6, pp. 419-426. https://doi.org/10.1515/jpem-2012-0053

APA

Cangul, H., Aycan, Z., Saglam, H., Forman, J. R., Cetinkaya, S., Tarim, O., Bober, E., Cesur, Y., Kurtoglu, S., Darendeliler, F., Bas, V., Eren, E., Demir, K., Kiraz, A., Aydin, B. K., Karthikeyan, A., Kendall, M., Boelaert, K., Shaw, N. J., ... Maher, E. R. (2012). TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis. Journal of pediatric endocrinology & metabolism, 25(5-6), 419-426. https://doi.org/10.1515/jpem-2012-0053

Vancouver

Author

Cangul, Hakan ; Aycan, Zehra ; Saglam, Halil ; Forman, Julia R ; Cetinkaya, Semra ; Tarim, Omer ; Bober, Ece ; Cesur, Yasar ; Kurtoglu, Selim ; Darendeliler, Feyza ; Bas, Veysel ; Eren, Erdal ; Demir, Korcan ; Kiraz, Aslihan ; Aydin, Banu K ; Karthikeyan, Ambika ; Kendall, Michaela ; Boelaert, Kristien ; Shaw, Nick J ; Kirk, Jeremy ; Hogler, Wolfgang ; Barrett, Timothy G ; Maher, Eamonn R. / TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis. In: Journal of pediatric endocrinology & metabolism. 2012 ; Vol. 25, No. 5-6. pp. 419-426.

Bibtex

@article{c53ac50fcd364c1c80e2f189bb2de775,
title = "TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis",
abstract = "Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.",
author = "Hakan Cangul and Zehra Aycan and Halil Saglam and Forman, {Julia R} and Semra Cetinkaya and Omer Tarim and Ece Bober and Yasar Cesur and Selim Kurtoglu and Feyza Darendeliler and Veysel Bas and Erdal Eren and Korcan Demir and Aslihan Kiraz and Aydin, {Banu K} and Ambika Karthikeyan and Michaela Kendall and Kristien Boelaert and Shaw, {Nick J} and Jeremy Kirk and Wolfgang Hogler and Barrett, {Timothy G} and Maher, {Eamonn R}",
year = "2012",
month = jun,
doi = "10.1515/jpem-2012-0053",
language = "English",
volume = "25",
pages = "419--426",
journal = "Journal of pediatric endocrinology & metabolism",
issn = "0334-018X",
publisher = "De Gruyter",
number = "5-6",

}

RIS

TY - JOUR

T1 - TSHR is the main causative locus in autosomal recessively inherited thyroid dysgenesis

AU - Cangul, Hakan

AU - Aycan, Zehra

AU - Saglam, Halil

AU - Forman, Julia R

AU - Cetinkaya, Semra

AU - Tarim, Omer

AU - Bober, Ece

AU - Cesur, Yasar

AU - Kurtoglu, Selim

AU - Darendeliler, Feyza

AU - Bas, Veysel

AU - Eren, Erdal

AU - Demir, Korcan

AU - Kiraz, Aslihan

AU - Aydin, Banu K

AU - Karthikeyan, Ambika

AU - Kendall, Michaela

AU - Boelaert, Kristien

AU - Shaw, Nick J

AU - Kirk, Jeremy

AU - Hogler, Wolfgang

AU - Barrett, Timothy G

AU - Maher, Eamonn R

PY - 2012/6

Y1 - 2012/6

N2 - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.

AB - Congenital hypothyroidism (CH) is the most common neonatal endocrine disorder and results in mental retardation if untreated. Eighty-five percent of CH cases are due to disruptions in thyroid organogenesis and are mostly sporadic, but about 2% of thyroid dysgenesis is familial, indicating the involvement of genetic factors in the aetiology of the disease. In this study, we aimed to investigate the Mendelian (single-gene) causes of non-syndromic and non-goitrous congenital hypothyroidism (CHNG) in consanguineous or multi-case families. Here we report the results of the second part (n=105) of our large cohort (n=244), representing the largest such cohort in the literature, and interpret the overall results of the whole cohort. Additionally, 50 sporadic cases with thyroid dysgenesis and 400 unaffected control subjects were included in the study. In familial cases, first, we performed potential linkage analysis of four known genes causing CHNG (TSHR, PAX8, TSHB, and NKX2-5) using microsatellite markers and then examined the presence of mutations in these genes by direct sequencing. In addition, in silico analyses of the predicted structural effects of TSHR mutations were performed and related to the mutation specific disease phenotype. We detected eight new TSHR mutations and a PAX8 mutation but no mutations in TSHB and NKX2-5. None of the biallelic TSHR mutations detected in familial cases were present in the cohort of 50 sporadic cases. Genotype/phenotype relationships were established between TSHR mutations and resulting clinical presentations. Here we conclude that TSHR mutations are the main detectable cause of autosomal recessively inherited thyroid dysgenesis. We also outline a new genetic testing strategy for the investigation of suspected autosomal recessive non-goitrous CH.

U2 - 10.1515/jpem-2012-0053

DO - 10.1515/jpem-2012-0053

M3 - Article

C2 - 22876533

VL - 25

SP - 419

EP - 426

JO - Journal of pediatric endocrinology & metabolism

JF - Journal of pediatric endocrinology & metabolism

SN - 0334-018X

IS - 5-6

ER -