exudates and Goiter--Nodular

Pendred syndrome (PDS, MIM #274600) is an autosomal recessive disorder characterized by congenital sensorineural hearing loss and goiter. In this study, we describing the possible PDS causal mutations in a Malaysian family with 2 daughters diagnosed with bilateral hearing loss and hypothyroidism.. Whole exome sequencing was performed on 2 sisters with PDS and their unaffected parents. Our results showed that both sisters inherited monoallelic mutations in the 2 known PDS genes, SLC26A4 (ENST00000265715:c.1343C > T, p.Ser448Leu) and GJB2 (ENST00000382844:c.368C > A, p.Thr123Asn) from their father, as well as another deafness-related gene, SCARB2 (ENST00000264896:c.914C > T, p.Thr305Met) from their mother. We postulated that these three heterozygous mutations in combination may be causative to deafness, and warrants further investigation. Furthermore, we also identified a compound heterozygosity involving the DUOX2 gene (ENST00000603300:c.1588A > T:p.Lys530* and c.3329G > A:p.Arg1110Gln) in both sisters which are inherited from both parents and may be correlated with early onset of goiter. All the candidate mutations were predicted deleterious by in silico tools.. In summary, we proposed that PDS in this family could be a polygenic disorder which possibly arises from a combination of heterozygous mutations in SLC26A4, GJB2 and SCARB2 which associated with deafness, as well as compound heterozygous DUOX2 mutations which associated with thyroid dysfunction.

Topics: Adolescent; Child; Connexin 26; Connexins; Dual Oxidases; Exome Sequencing; Female; Gene Expression Regulation; Goiter, Nodular; Hearing Loss, Sensorineural; Humans; Lysosomal Membrane Proteins; Malaysia; Membrane Transport Proteins; Mutation; Receptors, Scavenger; Sulfate Transporters

To investigate RET and p53 expression in local thyroid lesions, in order to shed light on the pathogenesis of papillary carcinoma and explain the high prevalence of this condition among the nodular hyperplasia (multi-nodular goitre) cases.. Archival thyroid tissue was retrieved from Hospital Universiti Sains Malaysia (HUSM) Pathology Department files and studied by immunohistochemistry for RET and p53 mutant protein. Normal tissues from 74 cases served as controls.. Fifty follicular adenoma, 66 nodular hyperplasia and 53 papillary carcinoma cases were studied. RET was expressed in 5.4% of normal thyroid tissue, 18% of follicular adenomas, 22.7% of nodular hyperplasia cases and 71.7% of papillary carcinomas. Its expression in papillary carcinoma was not associated with the coexistence of nodular hyperplasia lesions. p53 was expressed by 17% of papillary carcinomas. No association was found between p53 expression of nodular hyperplasia with or without co-existing papillary carcinoma. p53, rather than RET, was an excellent predictor of tumour lymph node metastasis and capsular invasion. p53 was also a significant prognosticator of survival outcome.. RET expression is highly prevalent in local papillary carcinoma, indicating a significant role in the pathogenesis of this tumour, with no apparent role in tumour behaviour and survival outcome. p53 on the other hand appears to be a significant factor in the latter events. The two genes appear to act in two different pathways: the former being an initiator, and the later a propagator of papillary carcinoma.

Topics: Adenocarcinoma, Papillary; Adenoma; Adolescent; Adult; Aged; Female; Goiter, Nodular; Humans; Immunoenzyme Techniques; Malaysia; Male; Middle Aged; Mutation; Neoplasm Recurrence, Local; Proto-Oncogene Proteins; Proto-Oncogene Proteins c-ret; Receptor Protein-Tyrosine Kinases; Survival Rate; Thyroid Neoplasms; Thyroidectomy; Tumor Suppressor Protein p53

A retrospective review of 107 patients operated on for multinodular goitre was carried out to determine the incidence of carcinoma. Of the group 7.5 per cent harboured incidental carcinomas with papillary carcinoma being the most common variety. The indications for removal of multinodular goitre should be compressive symptoms, suspicion of malignancy and cosmesis.

Topics: Adolescent; Adult; Aged; Carcinoma, Papillary; Female; Goiter, Nodular; Humans; Incidence; Malaysia; Male; Middle Aged; Retrospective Studies; Thyroid Neoplasms; Thyroidectomy