Rare Diseases Symptoms Automatic Extraction

Molecular and functional studies of 4 candidate loci in Pendred syndrome and nonsyndromic hearing loss.

[pendred syndrome]

Patients with PS or non-syndromic deafness were submitted to genetic/functional analyzes of SLC26A4, of its binding domain for FOXI1 (FOXI1-DBD), of the transcription activator FOXI1, and of the potassium channel KCNJ10. SLC26A4 was the most frequently mutated gene. An altered intracellular localization with immunocytochemistry, and a hampered maturation process were demonstrated for two novel SLC26A4 variants. Biochemical and immunocytochemical analyzes led to the development of a more sensitive fluorometric functional assay able to reveal the partial loss-of-function of SLC26A4 mutations. A novel missense variant was found in FOXI1 gene, though functional analysis showed no significant impairment in the transcriptional activation of SLC26A4. Finally, 3 patients were found to harbor a variant in KCNJ10, which was classified as polymorphism. The novelty of the study resides in the analysis of all the 4 candidate genetic loci linked to PS/non-syndromic deafness, and in the precise definition of the thyroid phenotype. PS was invariably associated with biallelic mutations of SLC26A4, whereas the genetic origin of non-syndromic deafness remained largely undetermined, since monoallelic SLC26A4 variants accounted for one fourth of the cases and FOXI1 and KCNJ10 were not involved in this series.

Diseases presenting "deafness" symptom

  • dentinogenesis imperfecta
  • epidermolysis bullosa simplex
  • hirschsprung disease
  • kabuki syndrome
  • kallmann syndrome
  • megacystis-microcolon-intestinal hypoperistalsis syndrome
  • neonatal adrenoleukodystrophy
  • oculocutaneous albinism
  • pendred syndrome
  • von hippel-lindau disease
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy

This symptom has already been validated