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A novel frameshift mutation in Allan-Herndon-Dudley syndrome

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Abstract

Allan-Herndon-Dudley syndrome (AHDS) is a very rare, X-linked psychomotor disability syndrome with delayed myelination, almost exclusively affecting boys. We present a case of a 4-year-old boy with AHDS who was found cyanotic, with intermittent vomiting and paroxysmal convulsions about 4 h after his parents went out, and was then taken to the hospital, where he eventually died the next day. The autopsy revealed foreign bodies in the tiny bronchi and alveoli of the deceased, congestion, and punctate hemorrhage in multiple organs, consistent with the diagnosis of asphyxia. Compared with a normally developing 4-year-old boy, the deceased showed cerebral atrophy and cerebral edema, and Luxol Fast Blue (LFB) stain indicated delayed cerebellar, hippocampal, and basal ganglia development and myelination. A novel frameshift mutation c.584delG in the SLC16A2 gene was detected. Family lineage investigation showed that the mutation was also detected in the deceased’s 8-year-old brother and biological mother. The present work enriches the profile mutations in SLC16A2 related to AHDS and emphasizes the importance of autopsy and postmortem genetic analysis in such cases.

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References

  1. Dumitrescu AM, Liao XH, Best TB, Brockmann K, Refetoff S (2004) A novel syndrome combining thyroid and neurological abnormalities is associated with mutations in a monocarboxylate transporter gene. Am J Hum Genet 74:168–175. https://doi.org/10.1086/380999

    Article  CAS  PubMed  Google Scholar 

  2. Allan W, Herndon CN, Dudley FC (1944) Some examples of the inheritance of mental deficiency: apparently sex-linked idiocy and microcephaly. Am J Ment Defic 48:325–334

    Google Scholar 

  3. Schwartz CE, May MM, Carpenter NJ et al (2005) Allan–Herndon–Dudley syndrome and the monocarboxylate transporter 8 (MCT8) gene. Am J Hum Genet 77:41–53. https://doi.org/10.1086/431313

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  4. Schwartz CE, Stevenson RE (2007) The MCT8 thyroid hormone transporter and Allan-Herndon-Dudley syndrome. Best Pract Res Clin Endocrinol Metab 21(2):307–321. https://doi.org/10.1016/j.beem.2007.03.009

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Friesema EC, Grueters A, Biebermann H, Krude H, von Moers A, Reeser M, Barrett TG, Mancilla EE, Svensson J, Kester MH, Kuiper GG, Balkassmi S, Uitterlinden AG, Koehrle J, Rodien P, Halestrap AP, Visser TJ (2004) Association between mutations in a thyroid hormone transporter and severe X-linked psychomotor retardation. Lancet 364(9443):1435–7. https://doi.org/10.1016/S0140-6736(04)17226-7

    Article  CAS  PubMed  Google Scholar 

  6. Vaurs-Barrière C, Deville M, Sarret C et al (2009) Pelizaeus–Merzbacher-like disease presentation of MCT8 mutated male subjects. Ann Neurol 65:114–118. https://doi.org/10.1002/ana.21579

    Article  CAS  PubMed  Google Scholar 

  7. Namba N, Etani Y, Kitaoka T et al (2008) Clinical phenotype and endocrinological investigations in a patient with a mutation in the MCT8 thyroid hormone transporter. Eur J Pediatr 167:785–791. https://doi.org/10.1007/s00431-007-0589-6

    Article  PubMed  Google Scholar 

  8. Gika AD, Siddiqui A, Hulse AJ et al (2010) White matter abnormalities and dystonic motor disorder associated with mutations in the SLC16A2 gene. Dev Med Child Neurol 52:475–482. https://doi.org/10.1111/j.1469-8749.2009.03471.x

    Article  PubMed  Google Scholar 

  9. Friesema EC, Ganguly S, Abdalla A, Manning Fox JE, Halestrap AP, Visser TJ (2003) Identification of monocarboxylate transporter 8 as a specific thyroid hormone transporter. J Biol Chem 278:40128–40135. https://doi.org/10.1074/jbc.M300909200

    Article  CAS  PubMed  Google Scholar 

  10. Visser WE, Vrijmoeth P, Visser FE, Arts WF, van Toor H, Visser TJ (2013) Identification, functional analysis, prevalence and treatment of monocarboxylate transporter 8 (MCT8) mutations in a cohort of adult patients with mental retardation. Clin Endocrinol (Oxf) 78(2):310–315. https://doi.org/10.1111/cen.12023

    Article  CAS  Google Scholar 

  11. Biebermann H, Ambrugger P, Tarnow P, von Moers A, Schweizer U, Grueters A (2005) Extended clinical phenotype, endocrine investigations and functional studies of a loss-of-function mutation A150V in the thyroid hormone specific transporter MCT8. Eur J Endocrinol 153:359–366. https://doi.org/10.1530/eje.1.01980

    Article  CAS  PubMed  Google Scholar 

  12. Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL, ACMG Laboratory Quality Assurance Committee (2015) Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med 17(5):405–24. https://doi.org/10.1038/gim.2015.30

    Article  PubMed  PubMed Central  Google Scholar 

  13. Gereben B, Zeöld A, Dentice M, Salvatore D, Bianco AC (2008) Activation and inactivation of thyroid hormone by deiodinases: local action with general consequences. Cell Mol Life Sci 65(4):570–590. https://doi.org/10.1007/s00018-007-7396-0

    Article  CAS  PubMed  Google Scholar 

  14. Remerand G, Boespflug-Tanguy O, Tonduti D, Touraine R, Rodriguez D, Curie A, Perreton N, Des Portes V, Sarret C, RMLX/AHDS Study Group (2019) Expanding the phenotypic spectrum of Allan-Herndon-Dudley syndrome in patients with SLC16A2 mutations. Dev Med Child Neurol 61(12):1439–1447. https://doi.org/10.1111/dmcn.14332

    Article  PubMed  Google Scholar 

  15. Groeneweg S, van Geest FS, Abacı A, Alcantud A, Ambegaonkar GP, Armour CM et al (2020) Disease characteristics of MCT8 deficiency: an international, retrospective, multicentre cohort study. Lancet Diabetes Endocrinol 8(7):594–605. https://doi.org/10.1016/S2213-8587(20)30153-4

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Geddes JF, Tasker RC, Hackshaw AK, Nickols CD, Adams GG, Whitwell HL, Scheimberg I (2003) Dural haemorrhage in non-traumatic infant deaths: does it explain the bleeding in ‘shaken baby syndrome’? Neuropathol Appl Neurobiol 29:14–22. https://doi.org/10.1046/j.1365-2990.2003.00434.x

    Article  CAS  PubMed  Google Scholar 

  17. Pollanen MS (2011) Subdural hemorrhage in infancy: keep an open mind. Forensic Sci Med Pathol 7(3):298–300. https://doi.org/10.1007/s12024-011-9238-5

    Article  PubMed  Google Scholar 

  18. Calzà L, Fernández M, Giardino L (2015) Role of the thyroid system in myelination and neural connectivity. Compr Physiol 5(3):1405–1421. https://doi.org/10.1002/cphy.c140035

    Article  PubMed  Google Scholar 

  19. van Tilborg E, de Theije CGM, van Hal M, Wagenaar N, de Vries LS, Benders MJ, Rowitch DH, Nijboer CH (2018) Origin and dynamics of oligodendrocytes in the developing brain: implications for perinatal white matter injury. Glia 66(2):221–238. https://doi.org/10.1002/glia.23256 (Epub 2017 Nov 14)

    Article  PubMed  Google Scholar 

  20. Schiffmann R, van der Knaap MS (2009) Invited article: an MRI-based approach to the diagnosis of white matter disorders. Neurology 72(8):750–9. https://doi.org/10.1212/01.wnl.0000343049.00540.c8

    Article  PubMed  PubMed Central  Google Scholar 

  21. Pouwels PJ, Vanderver A, Bernard G, Wolf NI, Dreha-Kulczewksi SF, Deoni SC, Bertini E, Kohlschütter A, Richardson W, Ffrench-Constant C, Köhler W, Rowitch D, Barkovich AJ (2014) Hypomyelinating leukodystrophies: translational research progress and prospects. Ann Neurol 76(1):5–19. https://doi.org/10.1002/ana.24194

    Article  PubMed  Google Scholar 

  22. Charzewska A, Wierzba J, Iżycka-Świeszewska E, Bekiesińska-Figatowska M, Jurek M, Gintowt A, Kłosowska A, Bal J, Hoffman-Zacharska D (2016) Hypomyelinating leukodystrophies - a molecular insight into the white matter pathology. Clin Genet 90(4):293–304. https://doi.org/10.1111/cge.12811

    Article  CAS  PubMed  Google Scholar 

  23. Klintschar M, Bilkenroth U, Arslan-Kirchner M, Schmidtke J, Stiller D (2009) Marfan syndrome: clinical consequences resulting from a medicolegal autopsy of a case of sudden death due to aortic rupture. Int J Legal Med 123(1):55–58. https://doi.org/10.1007/s00414-008-0288-5

    Article  CAS  PubMed  Google Scholar 

  24. Hugar BS, Praveen S, Kainoor SK, Shetty AR (2014) Sudden death in Marfan syndrome. J Forensic Sci 59:1126–1128. https://doi.org/10.1111/1556-4029.12415

    Article  PubMed  Google Scholar 

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Author notes

  1. Zihao Liu and Shuquan Zhao contributed equally to this work.

Authors and Affiliations

  1. Department of Forensic Medicine, Tongji Medical College, Huazhong University of Science and Technology, No. 13 Hangkong Road, Wuhan, 430030, People’s Republic of China

    Zihao Liu, Shuquan Zhao, Jianyi Chen, Longda Ma, Qing Shi & Yiwu Zhou

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  1. Zihao Liu
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  2. Shuquan Zhao
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  3. Jianyi Chen
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  4. Longda Ma
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  5. Qing Shi
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  6. Yiwu Zhou
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Correspondence to Yiwu Zhou.

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Liu, Z., Zhao, S., Chen, J. et al. A novel frameshift mutation in Allan-Herndon-Dudley syndrome. Int J Legal Med 136, 1181–1187 (2022). https://doi.org/10.1007/s00414-022-02823-z

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  • DOI: https://doi.org/10.1007/s00414-022-02823-z

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