Pulmonary fibrosis in dyskeratosis congenita: report of 2 cases

Dvorak, L; Vassallo, Robert; Kirmani, Salman; Johnson, Geoffrey B.; Hartman, Thomas E.; Tazelaar, Henry D.; Leslie, Kevin O.; Colby, Thomas V.; Cockcroft, Donald W.; Churg, Andrew; Yi, Eunhee S.

doi:10.1016/j.humpath.2014.10.003

Cited by 10 publications

(9 citation statements)

References 15 publications

(22 reference statements)

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“…We also found 13 variants of DKC1 in Asia with 100% male ( 7 , 9 , 13 , 20 , 23 , 28 , 32 , 35 , 36 , 40 ), 52 variants in non-Asia with 84.8% male ( 1 , 8 , 10 – 14 , 16 – 19 , 21 , 24 – 26 , 29 , 31 , 33 , 34 , 37 , 38 , 41 , 42 , 44 , 45 ), and 10 variants with unknown nationality ( 3 , 4 , 30 ). Asians develop DC at a younger age than non-Asians, between 4.3 and 46 years old ( 1 , 7 – 12 , 14 , 16 – 24 , 26 , 28 , 29 , 31 – 35 , 38 – 42 ).…”

Section: Discussionsupporting

confidence: 57%

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Wang

Xiong

et al. 2022

Front. Pediatr.

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BackgroundDyskeratosis congenita (DC) is a rare inheritable disorder characterized by bone marrow failure and mucocutaneous triad (reticular skin pigmentation, nail dystrophy, and oral leukoplakia). Dyskeratosis congenita 1 (DKC1) is responsible for 4.6% of the DC with an X-linked inheritance pattern. Almost 70 DKC1 variations causing DC have been reported in the Human Gene Mutation Database.ResultsHere we described a 14-year-old boy in a Chinese family with a phenotype of abnormal skin pigmentation on the neck, oral leukoplakia, and nail dysplasia in his hands and feet. Genetic analysis and sequencing revealed hemizygosity for a recurrent missense mutation c.1156G > A (p.Ala386Thr) in DKC1 gene. The heterozygous mutation (c.1156G > A) from his mother and wild-type sequence from his father were obtained in the same site of DKC1. This mutation was determined as disease causing based on silico software, but the pathological phenotypes of the proband were milder than previously reported at this position (HGMDCM060959). Homology modeling revealed that the altered amino acid was located near the PUA domain, which might affect the affinity for RNA binding.ConclusionThis DKC1 mutation (c.1156G > A, p.Ala386Thr) was first reported in a Chinese family with mucocutaneous triad phenotype. Our study reveals the pathogenesis of DKC1 c.1156G > A mutation to DC with a benign phenotype, which expands the disease variation database, the understanding of genotype–phenotype correlations, and facilitates the clinical diagnosis of DC in China.

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Section: Discussionsupporting

confidence: 57%

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Wang

Xiong

et al. 2022

Front. Pediatr.

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“…These findings are consistent with those previously described in lung tissue from DC subjects, which may also include a heterogeneous appearance due to alternating areas of normal lung, patchy interstitial inflammation, dense collagen deposition and honeycomb changes. 8 In contrast, lung GvHD usually has findings of intrabronchiolar T cells, apoptosis and perivenulitis. 9 Finally, several histologic features of the chronic phase of radiation-induced injury overlapped with that of our patient, including interstitial fibrosis and accumulation of foamy macrophages in pulmonary arteries and veins.…”

mentioning

confidence: 99%

Pulmonary complications post hematopoietic stem cell transplant in dyskeratosis congenita: analysis of oxidative stress in lung fibroblasts

Sorge

Pereboeva

Westin

et al. 2017

Bone Marrow Transplant

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“… 17 The mutation of DKC1, TERC and PARN genes is related to pulmonary fibrosis. 17 , 18 The clinical management of DC is complex, and allogeneic hematopoietic stem cell transplant (allo-HSCT) is the only curative therapy for bone marrow failure. 1 …”

Section: Discussionmentioning

confidence: 99%

A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita

Yuan¹,

Deng²,

Yang³

et al. 2022

CCID

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Purpose Dyskeratosis congenita (DC) is an inherited telomere biology disorder characterized clinically by mucocutaneous triad of reticulate hyperpigmentation, nail changes and oral leukoplakia. Bone marrow failure, pulmonary fibrosis and malignancies are the mainly life-threatening causes. There are X-linked recessive, autosomal dominant and autosomal recessive patterns of DC. DKC1 is the most common pathogenic mutation gene responsible for X-linked DC, and it encodes a protein, dyskerin, which is a component of telomerase holoenzyme complex essential for telomere maintenance. Patients with DC have very short telomeres, but the precise pathogenic mechanism remains unclear. This study aimed to identify the causative mutations in the DKC1 gene in three Chinese families with the X-linked form of DC. Patients and Methods Three Chinese families with DC were included in this study. Whole exome sequencing and Sanger sequencing were performed to clarify the mutation of DKC1 gene. Measurement of relative telomere length through qPCR. Predictions of protein structure and function were performed using bioinformatics tools, including I-TASSER, Polyphen-2 and SIFT. Results There were four males with DC and a female carrier in three Chinese pedigrees. The novel mutation c.92A>C (p. Q31P) and the missense mutation c.1058C>T (p. A353V) in DKC1 were identified. Both mutations locally changed the structure of dyskerin. Variant Q31P and A353V were predicted to have “deleterious” and “natural” effects on the function of dyskerin, respectively. Conclusion The novel variant and missense variant detected in the DKC1 gene improve our understanding of DC and broaden the mutation spectrum of the DKC1 gene.

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Pulmonary fibrosis in dyskeratosis congenita: report of 2 cases

Cited by 10 publications

References 15 publications

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Case Report: A Missense Mutation in Dyskeratosis Congenita 1 Leads to a Benign Form of Dyskeratosis Congenita Syndrome With the Mucocutaneous Triad

Pulmonary complications post hematopoietic stem cell transplant in dyskeratosis congenita: analysis of oxidative stress in lung fibroblasts

A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita

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