Identification of a founder mutation for Pendred syndrome in families from northwest Iran

Mohseni, Marzieh; Honarpour, Asal; Mozafari, Reza; Davarnia, Behzad; Najmabadi, Hossein; Kahrizi, Kimia

doi:10.1016/j.ijporl.2014.08.035

Cited by 8 publications

(6 citation statements)

References 12 publications

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“…www.nature.com/scientificreports/ Since geographic isolation and consanguinity-driven genomic homozygosity lead to the enrichment of rare founder mutations in specific societies or ethnic groups 7,9,51,52 , the presence of such mutations in our cohort of patients from related families is not surprising. Similar to other reports [53][54][55] , we identified two mutations that were present in more than one pedigree. The first, p.Ala189ArgfsTer130 in GUCY2D, was shared by two families originating from the Fars province in the Southwest of Iran and was found in a common ROH of 3.0 Mb with an identical haplotype.…”

Section: Discussionsupporting

confidence: 88%

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Rehman

Sepahi

Bedoni

et al. 2021

Sci Rep

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Inherited retinal dystrophies (IRDs) constitute one of the most heterogeneous groups of Mendelian human disorders. Using autozygome-guided next-generation sequencing methods in 17 consanguineous pedigrees of Iranian descent with isolated or syndromic IRD, we identified 17 distinct genomic variants in 11 previously-reported disease genes. Consistent with a recessive inheritance pattern, as suggested by pedigrees, variants discovered in our study were exclusively bi-allelic and mostly in a homozygous state (in 15 families out of 17, or 88%). Out of the 17 variants identified, 5 (29%) were never reported before. Interestingly, two mutations (GUCY2D:c.564dup, p.Ala189ArgfsTer130 and TULP1:c.1199G > A, p.Arg400Gln) were also identified in four separate pedigrees (two pedigrees each). In addition to expanding the mutational spectrum of IRDs, our findings confirm that the traditional practice of endogamy in the Iranian population is a prime cause for the appearance of IRDs.

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Section: Discussionsupporting

confidence: 88%

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Rehman

Sepahi

Bedoni

et al. 2021

Sci Rep

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“…The accumulation of specific PLP variants in certain populations can be a result of the founder effect, as it was evidenced for p.His723Arg in Japanese and Koreans and c.919-2A>G in Chinese [ 5 , 9 , 69 ]. The role of founder effect was also suggested in the prevalence of several other PLP variants in some local populations: p.Ser90Leu, p.Val239Asp, p.Gln446Arg in families from Pakistan [ 68 , 70 ], p.Val138Phe in German patients [ 71 ], c.965dup (p.Asn322LysfsTer8) in Iranian patients [ 72 ] and p.Gln514Arg in Spanish patients [ 36 ]. In addition, in our recent study [ 73 ], we revealed high frequencies of variant p.Leu676Gln, which is rare in other populations, and of a novel variant c.1545T>G (p.Phe515Leu), which both explain a significant part of the SLC26A4 -related HL in Tuvinian patients belonging to indigenous Turkic-speaking people living in the Tyva Republic (Southern Siberia, Russia).…”

Section: Discussionmentioning

confidence: 99%

Selection of Diagnostically Significant Regions of the SLC26A4 Gene Involved in Hearing Loss

Danilchenko

Zytsar

Maslova

et al. 2022

IJMS

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Screening pathogenic variants in the SLC26A4 gene is an important part of molecular genetic testing for hearing loss (HL) since they are one of the common causes of hereditary HL in many populations. However, a large size of the SLC26A4 gene (20 coding exons) predetermines the difficulties of its complete mutational analysis, especially in large samples of patients. In addition, the regional or ethno-specific prevalence of SLC26A4 pathogenic variants has not yet been fully elucidated, except variants c.919-2A>G and c.2168A>G (p.His723Arg), which have been proven to be most common in Asian populations. We explored the distribution of currently known pathogenic and likely pathogenic (PLP) variants across the SLC26A4 gene sequence presented in the Deafness Variation Database for the selection of potential diagnostically important parts of this gene. As a result of this bioinformatic analysis, we found that molecular testing ten SLC26A4 exons (4, 6, 10, 11, 13–17 and 19) with flanking intronic regions can provide a diagnostic rate of 61.9% for all PLP variants in the SLC26A4 gene. The primary sequencing of these SLC26A4 regions may be applied as an initial effective diagnostic testing in samples of patients of unknown ethnicity or as a subsequent step after the targeted testing of already-known ethno- or region-specific pathogenic SLC26A4 variants.

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“…One of these families was reported to have members with either DFNB4 or atypical PDS; the individuals from the other family were found to have severe to profound HL [ 17 ]. Moreover, three studies were reported from the Iranian population and described variable inter- and intra-familial manifestations in the SLC26A4 -related phenotypes [ 18 , 19 , 20 ]. Collectively, these findings highlight that inter-and intra-familial variability of SLC26A4- related phenotypes in the Middle East region can be evident in reports of certain countries but not others.…”

Section: Discussionmentioning

confidence: 99%

“…Only a few studies have been reported from Middle Eastern countries investigating the phenotypes associated with SLC26A4 [ 16 , 17 , 18 , 19 , 20 ]. These studies were conducted on patients from the United Arab Emirates (UAE), Iran, and Palestine [ 16 , 17 , 18 , 19 , 20 ]. Interestingly, intra- and inter-familial variabilities were observed in some of these studies.…”

Section: Introductionmentioning

confidence: 99%

SLC26A4 Phenotypic Variability Influences Intra- and Inter-Familial Diagnosis and Management

Tawalbeh

Aburizeg

Alragheb

et al. 2022

Genes

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SLC26A4 is one of the most common genes causing autosomal recessive non-syndromic sensorineural hearing loss (SNHL). It has been reported to cause Pendred Syndrome (PDS) and DFNB4 which is deafness with enlarged vestibular aqueduct (EVA). However, mutated SLC26A4 is not conclusive for having either DFNB4 or PDS. Three unrelated Jordanian families consisting of eight affected individuals with congenital bilateral hearing loss (HL) participated in this study. Whole-exome and Sanger sequencing were performed to investigate the underlying molecular etiology of HL. Further clinical investigations, including laboratory blood workup for the thyroid gland, CT scan for the temporal bone, and thyroid ultrasound were performed. Three disease-causing variants were identified in SLC26A4 in the three families, two of which were novel. Two families had a novel pathogenic homozygous splice-site accepter variant (c.165-1G>C), while the third family had compound heterozygous pathogenic variants (c.1446G>A; p.Trp482* and c.304G>A; p.Gly102Arg). Our approach helped in redirecting the diagnosis of several affected members of three different families from non-syndromic HL to syndromic HL. Two of the affected individuals had typical PDS, one had DFNB4, while the rest had atypical PDS. Our work emphasized the intra- and inter-familial variability of SLC26A4-related phenotypes. In addition, we highlighted the variable phenotypic impact of SLC26A4 on tailoring a personalized healthcare management.

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Identification of a founder mutation for Pendred syndrome in families from northwest Iran

Cited by 8 publications

References 12 publications

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Whole exome sequencing in 17 consanguineous Iranian pedigrees expands the mutational spectrum of inherited retinal dystrophies

Selection of Diagnostically Significant Regions of the SLC26A4 Gene Involved in Hearing Loss

SLC26A4 Phenotypic Variability Influences Intra- and Inter-Familial Diagnosis and Management

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