Segregation of a new mutation in SLC26A4 and p.E47X mutation in GJB2 within a consanguineous Tunisian family affected with Pendred syndrome

Said, Mariem Ben; Dhouib, H.; Benzina, Z.; Ghorbel, A.; Moreno, Felipe; Masmoudi, Saber; Ayadi, Hammadi; Hmani-Aifa, Mounira

doi:10.1016/j.ijporl.2012.02.053

Cited by 13 publications

(3 citation statements)

References 20 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Interestingly, both sisters were found inherited SLC26A4 and GJB2 monoallellic mutation from their unaffected father. Loss of function in both SLC26A4 and GJB2 have been implicated in syndromic and non-syndromic hearing loss [ 10 , 37 , 38 ]. Whilst SLC26A4 defects mainly attributed to syndromic hearing loss, GJB2 mutations accounts for up to 50% of all recessive non-syndromic hearing loss based on ethnic background [ 39 ].…”

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Chow

Murad

Rani

et al. 2017

Orphanet J Rare Dis

View full text Add to dashboard Cite

BackgroundPendred 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.Methods and ResultsWhole 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.ConclusionsIn 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.Electronic supplementary materialThe online version of this article (doi:10.1186/s13023-017-0575-7) contains supplementary material, which is available to authorized users.

show abstract

Section: Discussionmentioning

confidence: 99%

Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Chow

Murad

Rani

et al. 2017

Orphanet J Rare Dis

View full text Add to dashboard Cite

show abstract

“…The cosegregation of two genetic diseases in the same family, also known as comorbidity, has been previously reported in inbred populations from Middle East and North Africa [14,15,16,17,18]. In Tunisia, 75 comorbid associations have been described.…”

Section: Discussionmentioning

confidence: 86%

A Tunisian Patient with Two Rare Syndromes: Triple A Syndrome and Congenital Hypogonadotropic Hypogonadism

Abdallah

Lakhoua²,

Nagara³

et al. 2014

Horm Res Paediatr

View full text Add to dashboard Cite

Background/Aims: The coexistence of triple A syndrome (AAAS) and congenital hypogonadotropic hypogonadism (CHH) has so far not been reported in the literature. This study aimed to characterize at the clinical and genetic level one patient presenting an association of AAAS and CHH in order to identify causal mutations. Methods: Clinical and endocrinal investigations were performed and followed by mutational screening of candidate genes. Results: At the age of 18, the patient presented sexual infantilism, a micropenis and gynecomastia. No mutation was revealed in GnRHR, TACR3/TAC3, PROK2/PROKR2 and PROP1 genes, except a homozygous intronic variation (c.244 + 128C>T; dbSNP: rs350129) in the KISS1R gene, which is likely nondeleterious. A homozygous splice-donor site mutation (IVS14 + 1G>A) was found in the AAAS gene. This mutation, responsible for AAAS, is a founder mutation in North Africa. Conclusion: This is the first report on a Tunisian patient with the coexistence of AAAS and CHH. The diagnosis of CHH should be taken in consideration in patients with Allgrove syndrome and who carry the IVS14 + 1G>A mutation as this might challenge appropriate genetic counseling.

show abstract

“…The amino acid alignment of the SLC26A4 protein orthologs demonstrates that residue 71 is a conserved isoleucine suggesting that a substitution (ie Ile>Asn) at this position may have deleterious effects on the function of SLC26A4 protein (Figure 3d). To the best of our knowledge, we believe that this novel missense variation represents the fourth SLC26A4 mutation reported in Pendred syndrome‐Tunisian patients since 2000 (Charfeddine et al, 2010; Masmoudi et al, 2000; Rebeh et al, 2010; Ben Said et al, 2012). The association between SLC26A4 and autosomal recessive Pendred syndrome is well‐established and over 500 variants have been described (https://clinicalgenome.org/).…”

Section: Discussionmentioning

confidence: 93%

Custom Next‐Generation Sequencing Identifies Novel Mutations Expanding the Molecular and clinical spectrum of isolated Hearing Impairment or along with defects of the retina, the thyroid, and the kidneys

Said

Ayed

Elloumi

et al. 2022

Molec Gen & Gen Med

Self Cite

View full text Add to dashboard Cite

Background In the Tunisian population, the molecular analysis of hearing impairment remains based on conventional approaches, which makes the task laborious and enormously expensive. Exploration of the etiology of Hearing Impairment and the early diagnosis of causal mutations by next‐generation sequencing help significantly alleviate social and economic problems. Methods We elaborated a custom SureSelectQXT panel for next‐generation sequencing of the coding sequences of 42 genes involved in isolated hearing impairment or along with defects of the retina, the thyroid, and the kidneys. Results We report eight pathogenic variants, four of which are novel in patients with isolated hearing impairment, hearing impairment, and renal tubular acidosis, Usher syndrome and Pendred syndrome. Functional studies using molecular modeling showed the severe impact of the novel missense mutations on the concerned proteins. Basically, we identified mutations in nuclear as well as mitochondrial genes in a Tunisian family with isolated hearing impairment, which explains definitely the phenotype detected since 2006. Conclusion Our results expanded the mutation spectrum and genotype‒phenotype correlation of isolated and syndromic hearing loss and also emphasized the importance of combining both targeted next‐generation sequencing and detailed clinical evaluation to elaborate a more accurate diagnosis for hearing impairment and related phenotypes especially in North African populations.

show abstract

Segregation of a new mutation in SLC26A4 and p.E47X mutation in GJB2 within a consanguineous Tunisian family affected with Pendred syndrome

Cited by 13 publications

References 20 publications

Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

Exome sequencing identifies SLC26A4, GJB2, SCARB2 and DUOX2 mutations in 2 siblings with Pendred syndrome in a Malaysian family

A Tunisian Patient with Two Rare Syndromes: Triple A Syndrome and Congenital Hypogonadotropic Hypogonadism

Custom Next‐Generation Sequencing Identifies Novel Mutations Expanding the Molecular and clinical spectrum of isolated Hearing Impairment or along with defects of the retina, the thyroid, and the kidneys

Contact Info

Product

Resources

About