Rare Diseases Symptoms Automatic Extraction

A novel synonymous mutation causing complete skipping of exon 16 in the SLC26A4 gene in a Korean family with hearing loss.

[pendred syndrome]

Mutations in PDS (or SLC26A4) cause both Pendred syndrome (PS) and DFNB4, two autosomal recessive disorders that share hearing loss as a common feature. PS and DFNB4 are genetically homogeneous disorders caused by bi-allelic SLC26A4 mutations. Here, we report a novel synonymous mutation (c.1803G>A, p.Lys601Lys), that caused aberrant splicing in two Korean family members who were clinically considered to have DFNB4, along with congenital hearing loss and dilated vestibular aqueducts (DVA).After extracting DNA from whole blood using standard procedures, the 21 exons and flanking introns of SLC26A4 were amplified with PCR. To evaluate the implication of a novel synonymous mutation (c.1803G>A), we used The Berkeley Drosophila Genome Project (BDGP) (http://www.fruitfly.org/) as a splice site prediction program and performed exon trapping analysis.In molecular analysis of the 21 exons of SCL26A4, we detected a known splicing mutation (c.919-2A>G, heterozygote) and a novel variant (c.1803G>A, heterozygote) in the patients (II-1 and II-2). According to in silico analysis, the novel variant (c.1803G>A) affects canonical splice donor nucleotide positioning. To define the transcript level effects of this novel 1803G>A variant, we performed exon trapping and confirmed that exon 16 is completely skipped in this variant type.We report a novel synonymous mutation (c.1803G>A) causing complete exon 16 skipping in the SLC26A4 gene in two Korean family members with hearing loss. This is the first case of a synonymous SNP (c.1803G>A) affecting vestibulocochlear organs through altering splicing accuracy by causing a complete skipping of exon 16. An important issue raised by this study is that synonymous mutations that have been previously ignored in clinical diagnoses must now be considered as potential pathogenic mutations.

Diseases presenting "first case" symptom

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  • allergic bronchopulmonary aspergillosis
  • alpha-thalassemia
  • aniridia
  • aromatase deficiency
  • canavan disease
  • carcinoma of the gallbladder
  • child syndrome
  • cholangiocarcinoma
  • classical phenylketonuria
  • coats disease
  • cohen syndrome
  • congenital toxoplasmosis
  • cushing syndrome
  • cutaneous mastocytosis
  • dedifferentiated liposarcoma
  • dentin dysplasia
  • dracunculiasis
  • dystrophic epidermolysis bullosa
  • epidermolysis bullosa simplex
  • esophageal adenocarcinoma
  • esophageal carcinoma
  • fabry disease
  • familial mediterranean fever
  • focal myositis
  • gm1 gangliosidosis
  • harlequin ichthyosis
  • hodgkin lymphoma, classical
  • homocystinuria without methylmalonic aciduria
  • junctional epidermolysis bullosa
  • kabuki syndrome
  • krabbe disease
  • lamellar ichthyosis
  • legionellosis
  • liposarcoma
  • locked-in syndrome
  • malignant atrophic papulosis
  • monosomy 21
  • neonatal adrenoleukodystrophy
  • oculocutaneous albinism
  • omenn syndrome
  • papillon-lefèvre syndrome
  • pendred syndrome
  • pleomorphic liposarcoma
  • primary effusion lymphoma
  • primary hyperoxaluria type 1
  • proteus syndrome
  • pyomyositis
  • systemic capillary leak syndrome
  • thoracic outlet syndrome
  • von hippel-lindau disease
  • waldenström macroglobulinemia
  • well-differentiated liposarcoma
  • werner syndrome
  • wolf-hirschhorn syndrome
  • x-linked adrenoleukodystrophy

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