Detection of a new <scp>KCNQ</scp>1 frameshift mutation associated with Jervell and Lange‐Nielsen syndrome in 2 Iranian families

Amirian, Azam; Zafari, Zahra; Dalili, Mohammad; Saber, Siamak; Karimipoor, Morteza; Bagheri, Samira Dabbagh; Fazelifar, Amir Farjam; Zeinali, Sirous

doi:10.1002/joa3.12042

Cited by 3 publications

(3 citation statements)

References 29 publications

(45 reference statements)

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“…Examination of the parents of two patients showed heterozygosity for this mutation. In our previous study[15], using STR markers, we demonstrated this frameshift mutation in two obviously unrelated families with the same origin, which may represent a founding effect.…”

Section: Resultsmentioning

confidence: 84%

“…The sequence analysis of the index patient demonstrated the absence of mutation in the SCN5A and KCNH2 genes but showed a novel homozygous mutation, c.1426_1429delATGC (M476Pfs*4), in KCNQ1 gene. Five patients screened previously were found to have a missense mutation in two RWS families[16] and two frameshift mutations in three JLNS families[17,18].…”

Section: Discussionmentioning

confidence: 99%

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Identification of a Novel KCNQ1 Frameshift Mutation and Review of the Literature among Iranian Long QT Families

Amirian¹,

Zafari²,

Karimipoor³

et al. 2019

ibj

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Background: Long QT syndrome (LQTS) is characterized by the prolongation of QT interval, which results in syncope and sudden cardiac death in young people. KCNQ1 is the most common gene responsible for this syndrome. Methods: Molecular investigation was performed by DNA Sanger sequencing in Iranian families with a history of syncope. In silico examinations were performed for predicting the pathogenicity of the novel variant. Results: A novel homozygous KCNQ1 frameshift mutation, c.1426_1429delATGC (M476Pfs*4), was identified, and then the current literatures of five patients were reviewed regarding the LQTS. Conclusion: The novel frameshift mutation has been reported for the first time among the Iranian population. Our finding along with the case series study of LQTS patients illustrates the importance of genetic and case series in precise detection of the frequency of LQTS carriers.

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Section: Resultsmentioning

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Identification of a Novel KCNQ1 Frameshift Mutation and Review of the Literature among Iranian Long QT Families

Amirian¹,

Zafari²,

Karimipoor³

et al. 2019

ibj

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“…In addition to a homozygous frameshift mutation in USH2A, c.236_239dup p.(Gln81Tyrfs*28), proband 58 presented with a medically actionable pathogenic variant, c.733_734del p.(Gly245Argfs*39) in KCNQ1 (Table 1) (Amirian et al 2018), which is associated with long QT syndrome 1 (OMIM 192500) and familial atrial fibrillation 3 (OMIM 607554).…”

Section: Usher Syndrome As the Most Common Cause Of Dual Sensory Lossmentioning

confidence: 99%

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment

et al. 2021

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Usher syndrome, the most prevalent cause of combined hereditary vision and hearing impairment, is clinically and genetically heterogeneous. Moreover, several conditions with phenotypes overlapping Usher syndrome have been described. This makes the molecular diagnosis of hereditary deaf–blindness challenging. Here, we performed exome sequencing and analysis on 7 Mexican and 52 Iranian probands with combined retinal degeneration and hearing impairment (without intellectual disability). Clinical assessment involved ophthalmological examination and hearing loss questionnaire. Usher syndrome, most frequently due to biallelic variants in MYO7A (USH1B in 16 probands), USH2A (17 probands), and ADGRV1 (USH2C in 7 probands), was diagnosed in 44 of 59 (75%) unrelated probands. Almost half of the identified variants were novel. Nine of 59 (15%) probands displayed other genetic entities with dual sensory impairment, including Alström syndrome (3 patients), cone-rod dystrophy and hearing loss 1 (2 probands), and Heimler syndrome (1 patient). Unexpected findings included one proband each with Scheie syndrome, coenzyme Q10 deficiency, and pseudoxanthoma elasticum. In four probands, including three Usher cases, dual sensory impairment was either modified/aggravated or caused by variants in distinct genes associated with retinal degeneration and/or hearing loss. The overall diagnostic yield of whole exome analysis in our deaf–blind cohort was 92%. Two (3%) probands were partially solved and only 3 (5%) remained without any molecular diagnosis. In many cases, the molecular diagnosis is important to guide genetic counseling, to support prognostic outcomes and decisions with currently available and evolving treatment modalities.

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The Pathological Mechanisms of Hearing Loss Caused by KCNQ1 and KCNQ4 Variants

Homma

2022

Biomedicines

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Deafness-associated genes KCNQ1 (also associated with heart diseases) and KCNQ4 (only associated with hearing loss) encode the homotetrameric voltage-gated potassium ion channels Kv7.1 and Kv7.4, respectively. To date, over 700 KCNQ1 and over 70 KCNQ4 variants have been identified in patients. The vast majority of these variants are inherited dominantly, and their pathogenicity is often explained by dominant-negative inhibition or haploinsufficiency. Our recent study unexpectedly identified cell-death-inducing cytotoxicity in several Kv7.1 and Kv7.4 variants. Elucidation of this cytotoxicity mechanism and identification of its modifiers (drugs) have great potential for aiding the development of a novel pharmacological strategy against many pathogenic KCNQ variants. The purpose of this review is to disseminate this emerging pathological role of Kv7 variants and to underscore the importance of experimentally characterizing disease-associated variants.

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Detection of a new KCNQ1 frameshift mutation associated with Jervell and Lange‐Nielsen syndrome in 2 Iranian families

Cited by 3 publications

References 29 publications

Identification of a Novel KCNQ1 Frameshift Mutation and Review of the Literature among Iranian Long QT Families

Identification of a Novel KCNQ1 Frameshift Mutation and Review of the Literature among Iranian Long QT Families

Unraveling the genetic complexities of combined retinal dystrophy and hearing impairment

The Pathological Mechanisms of Hearing Loss Caused by KCNQ1 and KCNQ4 Variants

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