scholarly journals Identification of a frame shift mutation in the CCDC151 gene in a Han-Chinese family with Kartagener syndrome

2020 ◽  
Vol 40 (6) ◽  
Author(s):  
Sheng Deng ◽  
Shan Wu ◽  
Hong Xia ◽  
Wei Xiong ◽  
Xiong Deng ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Coiled Coil ◽  
Han Chinese ◽  
Chinese Family ◽  
Kartagener Syndrome ◽  
Coiled Coil Domain ◽  
Frame Shift ◽  
Frame Shift Mutation ◽  
Recessive Form ◽  
Ciliary Dyskinesia

Abstract Kartagener syndrome (KS), a subtype of primary ciliary dyskinesia (PCD), is characterized by bronchiectasis, chronic sinusitis, male infertility and situs inversus. KS is a genetically heterogeneous disease that is inherited in an autosomal recessive form; however, X-linked inheritance has also been reported. As of this writing [late 2020], at least 34 loci, most of which have known genes, have been reported in the literature as associating with KS. In the present study, we identified a frame shift mutation, c.167delG (p.G56Dfs*26), in the coiled-coil domain containing 151 gene (CCDC151) responsible for KS in a Han-Chinese family. To our knowledge, this is the first report of a CCDC151 c.167delG mutation in the KS patient. These findings may expand the CCDC151 mutation spectrum of KS, and contribute to future genetic counseling and gene-targeted therapy for this disease.

scholarly journals Gain-of-function human STAT1 mutations impair IL-17 immunity and underlie chronic mucocutaneous candidiasis

2011 ◽  
Vol 208 (8) ◽  
pp. 1635-1648 ◽  
Author(s):  
Luyan Liu ◽  
Satoshi Okada ◽  
Xiao-Fei Kong ◽  
Alexandra Y. Kreins ◽  
Sophie Cypowyj ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Coiled Coil ◽  
Cellular Responses ◽  
Chronic Mucocutaneous Candidiasis ◽  
Loss Of Function ◽  
Gain Of Function ◽  
Mucocutaneous Candidiasis ◽  
Coiled Coil Domain ◽  
Whole Exome ◽  
Ifn Γ

Chronic mucocutaneous candidiasis disease (CMCD) may be caused by autosomal dominant (AD) IL-17F deficiency or autosomal recessive (AR) IL-17RA deficiency. Here, using whole-exome sequencing, we identified heterozygous germline mutations in STAT1 in 47 patients from 20 kindreds with AD CMCD. Previously described heterozygous STAT1 mutant alleles are loss-of-function and cause AD predisposition to mycobacterial disease caused by impaired STAT1-dependent cellular responses to IFN-γ. Other loss-of-function STAT1 alleles cause AR predisposition to intracellular bacterial and viral diseases, caused by impaired STAT1-dependent responses to IFN-α/β, IFN-γ, IFN-λ, and IL-27. In contrast, the 12 AD CMCD-inducing STAT1 mutant alleles described here are gain-of-function and increase STAT1-dependent cellular responses to these cytokines, and to cytokines that predominantly activate STAT3, such as IL-6 and IL-21. All of these mutations affect the coiled-coil domain and impair the nuclear dephosphorylation of activated STAT1, accounting for their gain-of-function and dominance. Stronger cellular responses to the STAT1-dependent IL-17 inhibitors IFN-α/β, IFN-γ, and IL-27, and stronger STAT1 activation in response to the STAT3-dependent IL-17 inducers IL-6 and IL-21, hinder the development of T cells producing IL-17A, IL-17F, and IL-22. Gain-of-function STAT1 alleles therefore cause AD CMCD by impairing IL-17 immunity.

A novel frame-shift mutation of GLI3 causes non-syndromic and complex digital anomalies in a Chinese family

2011 ◽  
Vol 412 (11-12) ◽  
pp. 1012-1017 ◽  
Author(s):  
Feng Cheng ◽  
Xin Ke ◽  
Ming Lv ◽  
Fan Zhang ◽  
Chaohua Li ◽  
...  
Keyword(s):  
Chinese Family ◽  
Frame Shift ◽  
Frame Shift Mutation

scholarly journals Mutated CCDC51 Coding for a Mitochondrial Protein, MITOK Is a Candidate Gene Defect for Autosomal Recessive Rod-Cone Dystrophy

2021 ◽  
Vol 22 (15) ◽  
pp. 7875
Author(s):  
Christina Zeitz ◽  
Cécile Méjécase ◽  
Christelle Michiels ◽  
Christel Condroyer ◽  
Juliette Wohlschlegel ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Mitochondrial Protein ◽  
Coiled Coil ◽  
Cone Dystrophy ◽  
Gene Defect ◽  
Rare Mutation ◽  
Coiled Coil Domain ◽  
Retinal Disorders ◽  
First Time ◽  
Inherited Retinal Disorders

The purpose of this work was to identify the gene defect underlying a relatively mild rod-cone dystrophy (RCD), lacking disease-causing variants in known genes implicated in inherited retinal disorders (IRD), and provide transcriptomic and immunolocalization data to highlight the best candidate. The DNA of the female patient originating from a consanguineous family revealed no large duplication or deletion, but several large homozygous regions. In one of these, a homozygous frameshift variant, c.244_246delins17 p.(Trp82Valfs*4); predicted to lead to a nonfunctional protein, was identified in CCDC51. CCDC51 encodes the mitochondrial coiled-coil domain containing 51 protein, also called MITOK. MITOK ablation causes mitochondrial dysfunction. Here we show for the first time that CCDC51/MITOK localizes in the retina and more specifically in the inner segments of the photoreceptors, well known to contain mitochondria. Mitochondrial proteins have previously been implicated in IRD, although usually in association with syndromic disease, unlike our present case. Together, our findings add another ultra-rare mutation implicated in non-syndromic IRD, whose pathogenic mechanism in the retina needs to be further elucidated.

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