Medicine:Trichothiodystrophy

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Trichothiodystrophy (TTD) is an autosomal recessive inherited disorder characterised by brittle hair and intellectual impairment. The word breaks down into tricho – "hair", thio – "sulphur", and dystrophy – "wasting away" or literally "bad nourishment". TTD is associated with a range of symptoms connected with organs of the ectoderm and neuroectoderm. TTD may be subclassified into four syndromes: Approximately half of all patients with trichothiodystrophy have photosensitivity, which divides the classification into syndromes with or without photosensitivity; BIDS and PBIDS, and IBIDS and PIBIDS. Modern covering usage is TTD-P (photosensitive), and TTD.[1]

Presentation

Features of TTD can include photosensitivity, ichthyosis, brittle hair and nails, intellectual impairment, decreased fertility and short stature. A more subtle feature associated with this syndrome is a "tiger tail" banding pattern in hair shafts, seen in microscopy under polarized light.[2] The acronyms PIBIDS, IBIDS, BIDS and PBIDS give the initials of the words involved. BIDS syndrome, also called Amish brittle hair brain syndrome and hair-brain syndrome,[3] is an autosomal recessive[4] inherited disease. It is nonphotosensitive. BIDS is characterized by brittle hair, intellectual impairment, decreased fertility, and short stature.[5]: 501  There is a photosensitive syndrome, PBIDS.[6]

BIDS is associated with the gene MPLKIP (TTDN1).[7] IBIDS syndrome, following the acronym from ichthyosis, brittle hair and nails, intellectual impairment and short stature, is the Tay syndrome or sulfur-deficient brittle hair syndrome, first described by Tay in 1971.[8] (Chong Hai Tay was the Singaporean doctor who was the first doctor in South East Asia to have a disease named after him.[9]) Tay syndrome should not be confused with the Tay–Sachs disease.[5]: 485 [10][11][12] It is an autosomal recessive[13] congenital disease.[5]: 501 [14] In some cases, it can be diagnosed prenatally.[15] IBIDS syndrome is nonphotosensitive.

Cause

The photosensitive form is referred to as PIBIDS, and is associated with ERCC2/XPD[10] and ERCC3.[16]

Photosensitive forms

All photosensitive TTD syndromes have defects in the nucleotide excision repair (NER) pathway, which is a vital DNA repair system that removes many kinds of DNA lesions. This defect is not present in the nonphotosensitive TTD's.[17] These types of defects can result in other rare autosomal recessive diseases like xeroderma pigmentosum and Cockayne syndrome.[18]

DNA repair

Currently, mutations in four genes are recognized as causing the TTD phenotype, namely TTDN1, ERCC3/XPB, ERCC2/XPD and TTDA.[19] Individuals with defects in XPB, XPD and TTDA are photosensitive, whereas those with a defect in TTDN1 are not. The three genes, XPB, XPD and TTDA, encode protein components of the multi-subunit transcription/repair factor IIH (TFIIH). This complex factor is an important decision maker in NER that opens the DNA double helix after damage is initially recognized. NER is a multi-step pathway that removes a variety of different DNA damages that alter normal base pairing, including both UV-induced damages and bulky chemical adducts. Features of premature aging often occur in individuals with mutational defects in genes specifying protein components of the NER pathway, including those with TTD[20] (see DNA damage theory of aging).

Non-Photosensitive forms

The non-photosensitive forms are caused by AARS1, CARS1, TTDN1, RNF113A, TARS1 and MARS1 genes.[21] The function of AARS1, CARS1 and TARS1 gene are to charge tRNAs with amino acid.[22] According to one study, the TTDN1 gene plays role in mitosis.[23] Some study suggests that the RNF113A gene is a part of spliceosome and it can terminate CXCR4 pathway through CXCR4 Ubiquitination.[24][25][26]

RNF113A causes X-linked recessive form of TTD.[27]

Diagnosis

The diagnosis of TTD can by made by showing low sulfur content by biochemical assay of hair shafts, also, it can by following findings:[28]

  • Trichoschisis (broken or split hairs)
  • Alternating light and dark bands called 'tiger-tail pattern' are found in the hair shaft, which can be detected by polarised light microscopy or trichoscopy.
  • A severely damaged or absent hair cuticle can be seen by electron microscopy scanning.

Treatment

This disease doesn't have a cure, although it can be managed symptomatically.[29] Patients with Photosensetive forms should be provided with sun protection.[29][30]

See also

  • Skin lesion
  • List of cutaneous conditions

References

  1. ↑ Lambert WC, Gagna CE, Lambert MW (2010). "Trichothiodystrophy: Photosensitive, TTD-P, TTD, Tay Syndrome". Diseases of DNA Repair. Advances in Experimental Medicine and Biology. 685. pp. 106–10. doi:10.1007/978-1-4419-6448-9_10. ISBN 978-1-4419-6447-2. 
  2. ↑ Liang, Christine; Kraemer, Kenneth H.; Morris, Andrea; Schiffmann, Raphael; Price, Vera H.; Menefee, Emory; DiGiovanna, John J. (February 2005). "Characterization of tiger tail banding and hair shaft abnormalities in trichothiodystrophy". Journal of the American Academy of Dermatology 52 (2): 224–232. doi:10.1016/j.jaad.2004.09.013. PMID 15692466. 
  3. ↑ Online Mendelian Inheritance in Man (OMIM) 234050
  4. ↑ Baden, H. P.; Jackson, C. E.; Weiss, L.; Jimbow, K.; Lee, L.; Kubilus, J.; Gold, R. J. (Sep 1976). "The physicochemical properties of hair in the BIDS syndrome". American Journal of Human Genetics 28 (5): 514–521. PMID 984047. 
  5. ↑ 5.0 5.1 5.2 Freedberg, et al. (2003). Fitzpatrick's Dermatology in General Medicine. (6th ed.). McGraw-Hill. ISBN 0-07-138076-0.
  6. ↑ Hashimo S, and Egly JM. Trichothiodystrophy view from the molecular basis of DNA repair transcription factor TF11H.www.oxfordjournals.org/content/18/R2/R224
  7. ↑ "Identification of C7orf11 (TTDN1) gene mutations and genetic heterogeneity in nonphotosensitive trichothiodystrophy". Am. J. Hum. Genet. 76 (3): 510–6. March 2005. doi:10.1086/428141. PMID 15645389. 
  8. ↑ Tay CH (1971). "Ichthyosiform erythroderma, hair shaft abnormalities, and mental and growth retardation. A new recessive disorder". Arch Dermatol 104 (1): 4–13. doi:10.1001/archderm.104.1.4. PMID 5120162. 
  9. ↑ "A Pioneering Spirit". https://www.sma.org.sg/UploadedImg/files/Publications%20-%20SMA%20News/4506/Interview.pdf. 
  10. ↑ 10.0 10.1 Online Mendelian Inheritance in Man (OMIM) 601675
  11. ↑ Rapini, Ronald P.; Bolognia, Jean L.; Jorizzo, Joseph L. (2007). Dermatology: 2-Volume Set. St. Louis: Mosby. ISBN 978-1-4160-2999-1. 
  12. ↑ Hashimoto S, and Egly JM, www.oxfordjournals.org/content/18/R2/R224
  13. ↑ Stefanini M, B. E.; Botta, E.; Lanzafame, M.; Orioli, D. (January 2010). "Trichothiodystrophy: from basic mechanisms to clinical implications". DNA Repair 9 (1): 2–10. doi:10.1016/j.dnarep.2009.10.005. PMID 19931493. 
  14. ↑ James, William; Berger, Timothy; Elston, Dirk (2005). Andrews' Diseases of the Skin: Clinical Dermatology (10th ed.). Saunders. p. 575. ISBN 978-0-7216-2921-6. https://archive.org/details/andrewsdiseasess00mdwi_659. 
  15. ↑ "Prenatal diagnosis of xeroderma pigmentosum and trichothiodystrophy in 76 pregnancies at risk". Prenat. Diagn. 27 (12): 1133–1137. Dec 2007. doi:10.1002/pd.1849. PMID 17880036. 
  16. ↑ Online Mendelian Inheritance in Man (OMIM) 616390
  17. ↑ Hashimoto S, and Egly JM http://www.oxfordjournals.org/content/18/R2/R224
  18. ↑ Peserico, A.; Battistella, P. A.; Bertoli, P. (1 January 1992). "MRI of a very rare hereditary ectodermal dysplasia: PIBI(D)S". Neuroradiology 34 (4): 316–317. doi:10.1007/BF00588190. PMID 1528442. 
  19. ↑ "TTDA: big impact of a small protein". Exp. Cell Res. 329 (1): 61–8. 2014. doi:10.1016/j.yexcr.2014.07.008. PMID 25016283. 
  20. ↑ "Genome Instability in Development and Aging: Insights from Nucleotide Excision Repair in Humans, Mice, and Worms". Biomolecules 5 (3): 1855–69. 2015. doi:10.3390/biom5031855. PMID 26287260. 
  21. ↑ "Orphanet : Diseases". https://www.orpha.net/en/disease/gene/list/33364?mode=name. 
  22. ↑ Delarue, Marc (1995-02-01). "Aminoacyl-tRNA synthetases". Current Opinion in Structural Biology 5 (1): 48–55. doi:10.1016/0959-440X(95)80008-O. ISSN 0959-440X. PMID 7773747. https://www.sciencedirect.com/science/article/abs/pii/0959440X9580008O. 
  23. ↑ Zhang, Y.; Tian, Y.; Chen, Q.; Chen, D.; Zhai, Z.; Shu, H.-B. (2007-03-01). "TTDN1 is a Plk1-interacting protein involved in maintenance of cell cycle integrity" (in en). Cellular and Molecular Life Sciences 64 (5): 632–640. doi:10.1007/s00018-007-6501-8. ISSN 1420-9071. PMID 17310276. 
  24. ↑ Lear, Travis; Dunn, Sarah R.; McKelvey, Alison C.; Mir, Aazrin; Evankovich, John; Chen, Bill B.; Liu, Yuan (November 2017). "RING finger protein 113A regulates C-X-C chemokine receptor type 4 stability and signaling". American Journal of Physiology. Cell Physiology 313 (5): C584–C592. doi:10.1152/ajpcell.00193.2017. ISSN 0363-6143. PMID 28978524. 
  25. ↑ Zhang, Xiaofeng; Yan, Chuangye; Zhan, Xiechao; Li, Lijia; Lei, Jianlin; Shi, Yigong (March 2018). "Structure of the human activated spliceosome in three conformational states" (in en). Cell Research 28 (3): 307–322. doi:10.1038/cr.2018.14. ISSN 1748-7838. PMID 29360106. 
  26. ↑ Shostak, Kateryna; Jiang, Zheshen; Charloteaux, Benoit; Mayer, Alice; Habraken, Yvette; Tharun, Lars; Klein, Sebastian; Xu, Xinyi et al. (2020-03-09). "The X-linked trichothiodystrophy-causing gene RNF113A links the spliceosome to cell survival upon DNA damage" (in en). Nature Communications 11 (1): 1270. doi:10.1038/s41467-020-15003-7. ISSN 2041-1723. PMID 32152280. Bibcode: 2020NatCo..11.1270S. 
  27. ↑ Corbett, Mark A.; Dudding-Byth, Tracy; Crock, Patricia A.; Botta, Elena; Christie, Louise M.; Nardo, Tiziana; Caligiuri, Giuseppina; Hobson, Lynne et al. (2015-04-01). "A novel X-linked trichothiodystrophy associated with a nonsense mutation in RNF113A" (in en). Journal of Medical Genetics 52 (4): 269–274. doi:10.1136/jmedgenet-2014-102418. ISSN 0022-2593. PMID 25612912. https://jmg.bmj.com/content/52/4/269. 
  28. ↑ Hashimoto, Satoru; Egly, Jean Marc (2009-10-15). "Trichothiodystrophy view from the molecular basis of DNA repair/transcription factor TFIIH". Human Molecular Genetics 18 (R2): R224–R230. doi:10.1093/hmg/ddp390. ISSN 0964-6906. PMID 19808800. https://academic.oup.com/hmg/article-abstract/18/R2/R224/605065?redirectedFrom=fulltext&login=false. 
  29. ↑ 29.0 29.1 Faghri, S.; Tamura, D.; Kraemer, K. H.; DiGiovanna, J. J. (2008-10-01). "Trichothiodystrophy: a systematic review of 112 published cases characterises a wide spectrum of clinical manifestations" (in en). Journal of Medical Genetics 45 (10): 609–621. doi:10.1136/jmg.2008.058743. ISSN 0022-2593. PMID 18603627. PMC 3459585. https://jmg.bmj.com/content/45/10/609.long. 
  30. ↑ "Orphanet: Trichothiodystrophy". https://www.orpha.net/en/disease/detail/33364. 
Classification
External resources

Template:Congenital malformations and deformations of skin appendages



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