Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome

Ayça Kocaağa; Sevgi Yimenicioğlu; Veysel Nijat Baş; Oğuz Çilingir; Yaşar Bildirici

Case Report

Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome

Year 2022, Volume: 3 Issue: 2, 219 - 222, 01.08.2022

Ayça Kocaağa Sevgi Yimenicioğlu Veysel Nijat Baş Oğuz Çilingir Yaşar Bildirici

Abstract

Allan-Herndon-Dudley syndrome (AHDS) is a rare X-linked inherited disease that prevents absorption of thyroid hormone and causes axial hypotonia, weakness, and severe intellectual disability. The syndrome is caused by mutations in the SLC16A2 (known as MCT8) gene. This gene encodes the brain transporter of thyroid hormones. Deficiency of MCT8 leads to a lack of T3 entry in the brain, which causes central hypothyroidism. We described a boy who manifested congenital hypotonia, severe developmental delay, mental retardation, muscle weakness, and dystonia. He was diagnosed with AHDS which details the clinical and biochemical findings. A novel pathogenic nonsense (c.25G>T;p.E9X) mutation in the SLC16A2 gene was identified by direct sequencing. This case can expand the mutational spectrum of SLC16A2 gene mutations and support the clinical features of AHDS.

Keywords

MCT 8 defficiency, Hypotonia, SLC16A2 Gene, Thyroid hormone abnormality.

References

1. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014 Apr;94(2):355-82. PMID: 24692351; PMCID: PMC4044302. doi: 10.1152/physrev.00030.2013.
2. Maranduba CM, Friesema EC, Kok F, Kester MH, Jansen J, Sertié AL, Passos-Bueno MR, Visser TJ. Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. J Med Genet. 2006 May;43(5):457-60. Epub 2005 Jun 24. PMID: 15980113; PMCID: PMC2649011. doi: 10.1136/jmg.2005.035840.
3. Schwartz CE, Stevenson RE. The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):307-21. PMID: 17574010; PMCID: PMC2094733. doi: 10.1016/j.beem.2007.03.009.
4. Boccone L, Dessì V, Meloni A, Loudianos G. Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels. Eur J Med Genet. 2013 Apr;56(4):207-10. Epub 2013 Feb 16. PMID: 23419639. doi: 10.1016/j.ejmg.2013.02.001.
5. Armour CM, Kersseboom S, Yoon G, Visser TJ. Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One. 2015 Oct 1;10(10):e0139343. PMID: 26426690; PMCID: PMC4591285. doi: 10.1371/journal.pone.0139343.
6. Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005 Jul;77(1):41-53. Epub 2005 May 11. PMID: 15889350; PMCID: PMC1226193. doi: 10.1086/431313.
7. Groeneweg S, Visser WE, Visser TJ. Disorder of thyroid hormone transport into the tissues. Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):241-253. Epub 2017 May 24. PMID: 28648511. doi: 10.1016/j.beem.2017.05.001.
8. Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M. Allan-Herndon-Dudley-Syndrome: Considerations about the Brain Phenotype with Implications for Treatment Strategies. Exp Clin Endocrinol Diabetes. 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2. PMID: 32242326. doi: 10.1055/a-1108-1456.
9. van Geest FS, Meima ME, Stuurman KE, Wolf NI, van der Knaap MS, Lorea CF, Poswar FO, Vairo F, Brunetti-Pierri N, Cappuccio G, Bakhtiani P, de Munnik SA, Peeters RP, Visser WE, Groeneweg S. Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series. J Clin Endocrinol Metab. 2021 Jan 23;106(2):539-553. PMID: 33141165; PMCID: PMC7823235. doi: 10.1210/clinem/dgaa795.
10. Friesema EC, Visser WE, Visser TJ. Genetics and phenomics of thyroid hormone transport by MCT8. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):107-13. Epub 2010 Jan 18. PMID: 20083155. doi: 10.1016/j.mce.2010.01.016.
11. Yamamoto S, Okuhara K, Tonoki H, Iizuka S, Nihei N, Tajima T. A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome. Clin Pediatr Endocrinol. 2013 Oct;22(4):83-6. Epub 2013 Oct 26. PMID: 24170966; PMCID: PMC3809735. doi: 10.1292/cpe.22.83.
12. Rodrigues F, Grenha J, Ortez C, Nascimento A, Morte B, M-Belinchón M, Armstrong J, Colomer J. Hypotonic male infant and MCT8 deficiency - a diagnosis to think about. BMC Pediatr. 2014 Oct 4;14:252. PMID: 25284458; PMCID: PMC4287395. doi: 10.1186/1471-2431-14-252.
13. Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group. Expanding the phenotypic spectrum of Allan-Herndon-Dudley syndrome in patients with SLC16A2 mutations. Dev Med Child Neurol. 2019 Dec;61(12):1439-1447. Epub 2019 Aug 13. PMID: 31410843. doi: 10.1111/dmcn.14332.
14. Tonduti D, Vanderver A, Berardinelli A, Schmidt JL, Collins CD, Novara F, Genni AD, Mita A, Triulzi F, Brunstrom-Hernandez JE, Zuffardi O, Balottin U, Orcesi S. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol. 2013 Jun;28(6):795-800. Epub 2012 Jul 17. PMID: 22805248; PMCID: PMC4155008. doi: 10.1177/0883073812450944.
15. Vancamp P, Demeneix BA, Remaud S. Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination? Front Endocrinol (Lausanne). 2020 May 13;11:283. PMID: 32477268; PMCID: PMC7237703. doi: 10.3389/fendo.2020.00283.
16. Shimojima K, Maruyama K, Kikuchi M, Imai A, Inoue K, Yamamoto T. Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. Intractable Rare Dis Res. 2016 Aug;5(3):214-7. Erratum in: Intractable Rare Dis Res. 2017 Aug;6(3):E1. PMID: 27672545; PMCID: PMC4995413. doi: 10.5582/irdr.2016.01051.
17. Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M. Allan-Herndon-Dudley-Syndrome: Considerations about the Brain Phenotype with Implications for Treatment Strategies. Exp Clin Endocrinol Diabetes. 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2. PMID: 3224232. doi: 10.1055/a-1108-1456.

Allen-Herndon-Dudley Sendromunda yeni Bir Hemizigot SLC16A2 nonsense mutasyonu

Year 2022, Volume: 3 Issue: 2, 219 - 222, 01.08.2022

Ayça Kocaağa Sevgi Yimenicioğlu Veysel Nijat Baş Oğuz Çilingir Yaşar Bildirici

Abstract

Allan-Herndon-Dudley sendromu (AHDS), tiroid hormonunun emilimini önleyen ve aksiyal hipotoni, güçsüzlük ve ciddi zihinsel yetersizliğe yol açan, X'e bağlı, nadir görülen bir kalıtsal hastalıktır. SLC16A2 (MCT8 olarak bilinir) genindeki mutasyonlar hastalığa neden olmaktadır. Bu gen, tiroid hormonlarının beyine transferini sağlayan bir proteini kodlar. MCT8 eksikliği, beyinde merkezi hipotiroidizme neden olan T3 girişi eksikliğine yol açar. Doğuştan hipotoni, ciddi gelişim geriliği, zeka geriliği, kas güçsüzlüğü ve distoni ile kendini gösteren kliniğe sahip bir erkek çocuğu tanımladık. AHDS teşhisi kondu, klinik ve biyokimyasal bulguları detaylandırıldı. SLC16A2 genindeki yeni bir patojenik anlamsız (c.25G>T;p.E9X) mutasyon, SLC16A2 gen dizi analizi ile tanımlandı. Bu vaka, SLC16A2 gen mutasyonlarının mutasyonel spektrumunu genişletebilir ve AHDS'nin klinik özelliklerini destekleyebilir.

Keywords

MCT 8 eksikliği, Hipotoni, SLC16A2 Geni, Tiroid hormonu anormalliği.

References

1. Mullur R, Liu YY, Brent GA. Thyroid hormone regulation of metabolism. Physiol Rev. 2014 Apr;94(2):355-82. PMID: 24692351; PMCID: PMC4044302. doi: 10.1152/physrev.00030.2013.
2. Maranduba CM, Friesema EC, Kok F, Kester MH, Jansen J, Sertié AL, Passos-Bueno MR, Visser TJ. Decreased cellular uptake and metabolism in Allan-Herndon-Dudley syndrome (AHDS) due to a novel mutation in the MCT8 thyroid hormone transporter. J Med Genet. 2006 May;43(5):457-60. Epub 2005 Jun 24. PMID: 15980113; PMCID: PMC2649011. doi: 10.1136/jmg.2005.035840.
3. Schwartz CE, Stevenson RE. The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Pract Res Clin Endocrinol Metab. 2007 Jun;21(2):307-21. PMID: 17574010; PMCID: PMC2094733. doi: 10.1016/j.beem.2007.03.009.
4. Boccone L, Dessì V, Meloni A, Loudianos G. Allan-Herndon-Dudley syndrome (AHDS) in two consecutive generations caused by a missense MCT8 gene mutation. Phenotypic variability with the presence of normal serum T3 levels. Eur J Med Genet. 2013 Apr;56(4):207-10. Epub 2013 Feb 16. PMID: 23419639. doi: 10.1016/j.ejmg.2013.02.001.
5. Armour CM, Kersseboom S, Yoon G, Visser TJ. Further Insights into the Allan-Herndon-Dudley Syndrome: Clinical and Functional Characterization of a Novel MCT8 Mutation. PLoS One. 2015 Oct 1;10(10):e0139343. PMID: 26426690; PMCID: PMC4591285. doi: 10.1371/journal.pone.0139343.
6. Schwartz CE, May MM, Carpenter NJ, Rogers RC, Martin J, Bialer MG, Ward J, Sanabria J, Marsa S, Lewis JA, Echeverri R, Lubs HA, Voeller K, Simensen RJ, Stevenson RE. Allan-Herndon-Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet. 2005 Jul;77(1):41-53. Epub 2005 May 11. PMID: 15889350; PMCID: PMC1226193. doi: 10.1086/431313.
7. Groeneweg S, Visser WE, Visser TJ. Disorder of thyroid hormone transport into the tissues. Best Pract Res Clin Endocrinol Metab. 2017 Mar;31(2):241-253. Epub 2017 May 24. PMID: 28648511. doi: 10.1016/j.beem.2017.05.001.
8. Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M. Allan-Herndon-Dudley-Syndrome: Considerations about the Brain Phenotype with Implications for Treatment Strategies. Exp Clin Endocrinol Diabetes. 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2. PMID: 32242326. doi: 10.1055/a-1108-1456.
9. van Geest FS, Meima ME, Stuurman KE, Wolf NI, van der Knaap MS, Lorea CF, Poswar FO, Vairo F, Brunetti-Pierri N, Cappuccio G, Bakhtiani P, de Munnik SA, Peeters RP, Visser WE, Groeneweg S. Clinical and Functional Consequences of C-Terminal Variants in MCT8: A Case Series. J Clin Endocrinol Metab. 2021 Jan 23;106(2):539-553. PMID: 33141165; PMCID: PMC7823235. doi: 10.1210/clinem/dgaa795.
10. Friesema EC, Visser WE, Visser TJ. Genetics and phenomics of thyroid hormone transport by MCT8. Mol Cell Endocrinol. 2010 Jun 30;322(1-2):107-13. Epub 2010 Jan 18. PMID: 20083155. doi: 10.1016/j.mce.2010.01.016.
11. Yamamoto S, Okuhara K, Tonoki H, Iizuka S, Nihei N, Tajima T. A Novel Deletion Mutation of SLC16A2 Encoding Monocarboxylate Transporter (MCT) 8 in a 26-year-old Japanese Patient with Allan-Herndon-Dudley Syndrome. Clin Pediatr Endocrinol. 2013 Oct;22(4):83-6. Epub 2013 Oct 26. PMID: 24170966; PMCID: PMC3809735. doi: 10.1292/cpe.22.83.
12. Rodrigues F, Grenha J, Ortez C, Nascimento A, Morte B, M-Belinchón M, Armstrong J, Colomer J. Hypotonic male infant and MCT8 deficiency - a diagnosis to think about. BMC Pediatr. 2014 Oct 4;14:252. PMID: 25284458; PMCID: PMC4287395. doi: 10.1186/1471-2431-14-252.
13. Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C; RMLX/AHDS Study Group. Expanding the phenotypic spectrum of Allan-Herndon-Dudley syndrome in patients with SLC16A2 mutations. Dev Med Child Neurol. 2019 Dec;61(12):1439-1447. Epub 2019 Aug 13. PMID: 31410843. doi: 10.1111/dmcn.14332.
14. Tonduti D, Vanderver A, Berardinelli A, Schmidt JL, Collins CD, Novara F, Genni AD, Mita A, Triulzi F, Brunstrom-Hernandez JE, Zuffardi O, Balottin U, Orcesi S. MCT8 deficiency: extrapyramidal symptoms and delayed myelination as prominent features. J Child Neurol. 2013 Jun;28(6):795-800. Epub 2012 Jul 17. PMID: 22805248; PMCID: PMC4155008. doi: 10.1177/0883073812450944.
15. Vancamp P, Demeneix BA, Remaud S. Monocarboxylate Transporter 8 Deficiency: Delayed or Permanent Hypomyelination? Front Endocrinol (Lausanne). 2020 May 13;11:283. PMID: 32477268; PMCID: PMC7237703. doi: 10.3389/fendo.2020.00283.
16. Shimojima K, Maruyama K, Kikuchi M, Imai A, Inoue K, Yamamoto T. Novel SLC16A2 mutations in patients with Allan-Herndon-Dudley syndrome. Intractable Rare Dis Res. 2016 Aug;5(3):214-7. Erratum in: Intractable Rare Dis Res. 2017 Aug;6(3):E1. PMID: 27672545; PMCID: PMC4995413. doi: 10.5582/irdr.2016.01051.
17. Krude H, Biebermann H, Schuelke M, Müller TD, Tschöp M. Allan-Herndon-Dudley-Syndrome: Considerations about the Brain Phenotype with Implications for Treatment Strategies. Exp Clin Endocrinol Diabetes. 2020 Jun;128(6-07):414-422. Epub 2020 Apr 2. PMID: 3224232. doi: 10.1055/a-1108-1456.

There are 17 citations in total.

Details

Primary Language	English
Subjects	Health Care Administration
Journal Section	Case Report
Authors	Ayça Kocaağa 0000-0003-0434-8445 Sevgi Yimenicioğlu 0000-0002-1598-4423 Veysel Nijat Baş 0000-0001-6826-7025 Oğuz Çilingir 0000-0002-5593-4164 Yaşar Bildirici 0000-0002-4784-7810
Publication Date	August 1, 2022
Published in Issue	Year 2022 Volume: 3 Issue: 2

Cite

APA	Kocaağa, A., Yimenicioğlu, S., Baş, V. N., Çilingir, O., et al. (2022). Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome. Eskisehir Medical Journal, 3(2), 219-222.
AMA	Kocaağa A, Yimenicioğlu S, Baş VN, Çilingir O, Bildirici Y. Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome. Eskisehir Med J. August 2022;3(2):219-222.
Chicago	Kocaağa, Ayça, Sevgi Yimenicioğlu, Veysel Nijat Baş, Oğuz Çilingir, and Yaşar Bildirici. “Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome”. Eskisehir Medical Journal 3, no. 2 (August 2022): 219-22.
EndNote	Kocaağa A, Yimenicioğlu S, Baş VN, Çilingir O, Bildirici Y (August 1, 2022) Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome. Eskisehir Medical Journal 3 2 219–222.
IEEE	A. Kocaağa, S. Yimenicioğlu, V. N. Baş, O. Çilingir, and Y. Bildirici, “Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome”, Eskisehir Med J, vol. 3, no. 2, pp. 219–222, 2022.
ISNAD	Kocaağa, Ayça et al. “Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome”. Eskisehir Medical Journal 3/2 (August 2022), 219-222.
JAMA	Kocaağa A, Yimenicioğlu S, Baş VN, Çilingir O, Bildirici Y. Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome. Eskisehir Med J. 2022;3:219–222.
MLA	Kocaağa, Ayça et al. “Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome”. Eskisehir Medical Journal, vol. 3, no. 2, 2022, pp. 219-22.
Vancouver	Kocaağa A, Yimenicioğlu S, Baş VN, Çilingir O, Bildirici Y. Identification of A Novel Hemizygous SLC16A2 Nonsense Mutation in Allen-Herndon-Dudley Syndrome. Eskisehir Med J. 2022;3(2):219-22.

Download Cover Image

Article Files

Full Text

This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License.