Details of Disease

General Information of Disease (ID: DISZ1MU8)

• Disease Name: Pendred syndrome
• Synonyms: autosomal recessive sensorineural hearing impairment and goitre; autosomal recessive sensorineural hearing impairment and goiter; PDS; deafness with goitre; congenital hypothyroidism due to dyshormonogenesis 2B; hypothyroidism, congenital, due to dyshormonogenesis, 2B; Pendred syndrome; genetic defect in thyroid hormonogenesis 2B; goiter-deafness syndrome; TDH2B; deafness with goiter; thyroid hormonogenesis, genetic defect in, 2B; thyroid dyshormonogenesis 2B
• Definition: Pendred syndrome (PDS) is a clinically variable genetic disorder characterized by bilateral sensorineural hearing loss and euthyroid goiter.
• Disease Hierarchy:
  DIS6SVEE: Syndromic disease
  DISCPWH9: Autosomal recessive disease
  DISL5XVU: Congenital hypothyroidism
  DISZ1MU8: Pendred syndrome
• Disease Identifiers:
  MONDO ID: MONDO_0010134
  MESH ID: C536648
  UMLS CUI: C0271829
  OMIM ID: 274600
  MedGen ID: 82890
  Orphanet ID: 705
  SNOMED CT ID: 70348004

Molecular Interaction Atlas (MIA) of This Disease

This Disease Is Related to 8 DTT Molecule(s)

Gene Name	DTT ID	Evidence Level	Mode of Inheritance	REF
KCNJ10	TTG140O	Supportive	Autosomal recessive	[1]
F11	TTDM4ZU	moderate	Genetic Variation	[2]
KCNJ10	TTG140O	Strong	Genetic Variation	[3]
SLC13A5	TTFIMH7	Strong	Biomarker	[4]
SLC5A5	TTW7HI9	Strong	Genetic Variation	[5]
TPO	TT52XDZ	Strong	Genetic Variation	[6]
TSHR	TT6NYJA	Strong	Genetic Variation	[7]
SLC26A4	TT7X02I	Definitive	Genetic Variation	[8]

This Disease Is Related to 6 DTP Molecule(s)

Gene Name	DTP ID	Evidence Level	Mode of Inheritance	REF
SLC13A2	DTUO05P	Strong	Biomarker	[4]
SLC26A2	DTFSLX5	Strong	Genetic Variation	[9]
SLC26A3	DTN1FMD	Strong	Genetic Variation	[9]
SLC26A5	DTPGHJ7	Strong	Biomarker	[10]
SLC5A8	DTE3TAW	Strong	Genetic Variation	[5]
SLC26A4	DTGUASD	Definitive	Autosomal recessive	[11]

This Disease Is Related to 1 DME Molecule(s)

Gene Name	DME ID	Evidence Level	Mode of Inheritance	REF
PTGDS	DER3H9C	Strong	Biomarker	[12]

This Disease Is Related to 13 DOT Molecule(s)

Gene Name	DOT ID	Evidence Level	Mode of Inheritance	REF
MPZL2	OTKFNDUI	Limited	Biomarker	[13]
FOXI1	OT2UFOE2	Supportive	Autosomal recessive	[1]
KCNJ10	OTPL3Z8A	Supportive	Autosomal recessive	[1]
DNAJC14	OT7DPIVN	moderate	Biomarker	[14]
OTOF	OTXQMJY8	moderate	Genetic Variation	[15]
PTCRA	OTQTO5QZ	moderate	Genetic Variation	[2]
ALDH7A1	OTV57BZD	Strong	Genetic Variation	[16]
CLPP	OTEPHG0S	Strong	Genetic Variation	[17]
DUOX2	OTU14HCN	Strong	Genetic Variation	[18]
LYPD1	OT0HSGML	Strong	Genetic Variation	[19]
TBC1D24	OTKZUSMD	Strong	Genetic Variation	[17]
TG	OT3ELHIJ	Strong	Genetic Variation	[7]
SLC26A4	OTXUTLVS	Definitive	Autosomal recessive	[11]

References

• [1] Pendred Syndrome?/ Nonsyndromic Enlarged Vestibular Aqueduct. 1998 Sep 28 [updated 2020 Jun 18]. In: Adam MP, Feldman J, Mirzaa GM, Pagon RA, Wallace SE, Bean LJH, Gripp KW, Amemiya A, editors. GeneReviews(?) [Internet]. Seattle (WA): University of Washington, Seattle; 1993C2024.
• [2] A pathogenic variant in SLC26A4 is associated with Pendred syndrome in a consanguineous Iranian family.Int J Audiol. 2019 Oct;58(10):628-634. doi: 10.1080/14992027.2019.1619945. Epub 2019 Jun 12.
• [3] Lack of significant association between mutations of KCNJ10 or FOXI1 and SLC26A4 mutations in Pendred syndrome/enlarged vestibular aqueducts.BMC Med Genet. 2013 Aug 21;14:85. doi: 10.1186/1471-2350-14-85.
• [4] Primary debulking surgery versus primary neoadjuvant chemotherapy for high grade advanced stage ovarian cancer: comparison of survivals.Radiol Oncol. 2018 Sep 11;52(3):307-319. doi: 10.2478/raon-2018-0030.
• [5] Homology of pendrin, sodium-iodide symporter and apical iodide transporter.Front Biosci (Landmark Ed). 2018 Jun 1;23(10):1864-1873. doi: 10.2741/4677.
• [6] A systematic review of genetic studies of thyroid disorders in Taiwan.J Chin Med Assoc. 2015 Mar;78(3):145-53. doi: 10.1016/j.jcma.2014.09.010. Epub 2014 Nov 11.
• [7] Expression of iodine metabolism genes in human thyroid tissues: evidence for age and BRAFV600E mutation dependency.Clin Endocrinol (Oxf). 2009 Apr;70(4):629-35. doi: 10.1111/j.1365-2265.2008.03376.x. Epub 2008 Aug 15.
• [8] The Natural History of Hearing Loss in Pendred Syndrome and Non-Syndromic Enlarged Vestibular Aqueduct.Otol Neurotol. 2019 Mar;40(3):e178-e185. doi: 10.1097/MAO.0000000000002140.
• [9] Molecular analysis of human solute carrier SLC26 anion transporter disease-causing mutations using 3-dimensional homology modeling.Biochim Biophys Acta Biomembr. 2017 Dec;1859(12):2420-2434. doi: 10.1016/j.bbamem.2017.09.016. Epub 2017 Sep 21.
• [10] Pathogenetics of the human SLC26 transporters.Curr Med Chem. 2005;12(4):385-96. doi: 10.2174/0929867053363144.
• [11] Technical standards for the interpretation and reporting of constitutional copy-number variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics (ACMG) and the Clinical Genome Resource (ClinGen). Genet Med. 2020 Feb;22(2):245-257. doi: 10.1038/s41436-019-0686-8. Epub 2019 Nov 6.
• [12] Insulin-like growth factor type I selectively binds to G-quadruplex structures.Biochim Biophys Acta Gen Subj. 2019 Jan;1863(1):31-38. doi: 10.1016/j.bbagen.2018.09.022. Epub 2018 Sep 29.
• [13] Analysis of the thyroid phenotype in 42 patients with Pendred syndrome and nonsyndromic enlargement of the vestibular aqueduct.Thyroid. 2014 Apr;24(4):639-48. doi: 10.1089/thy.2013.0164. Epub 2014 Jan 20.
• [14] The HSP70 co-chaperone DNAJC14 targets misfolded pendrin for unconventional protein secretion.Nat Commun. 2016 Apr 25;7:11386. doi: 10.1038/ncomms11386.
• [15] Deafness heterogeneity in a Druze isolate from the Middle East: novel OTOF and PDS mutations, low prevalence of GJB2 35delG mutation and indication for a new DFNB locus.Eur J Hum Genet. 2000 Jun;8(6):437-42. doi: 10.1038/sj.ejhg.5200489.
• [16] Long-term follow-up in two siblings with pyridoxine-dependent seizures associated with a novel ALDH7A1 mutation.Eur J Paediatr Neurol. 2011 Nov;15(6):547-50. doi: 10.1016/j.ejpn.2011.05.011. Epub 2011 Jul 5.
• [17] Unresolved questions regarding human hereditary deafness.Oral Dis. 2017 Jul;23(5):551-558. doi: 10.1111/odi.12516. Epub 2016 Jul 11.
• [18] Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family.Orphanet J Rare Dis. 2017 Feb 21;12(1):40. doi: 10.1186/s13023-017-0575-7.
• [19] Familial follicular cell tumors: classification and morphological characteristics.Endocr Pathol. 2010 Dec;21(4):219-26. doi: 10.1007/s12022-010-9135-6.