Clinical, Cosmetic and Investigational Dermatology (Sep 2022)
A Novel Variant and a Missense Variant Identified in the DKC1 Gene in Three Chinese Familieswith Dyskeratosis Congenita
Abstract
Chunyu Yuan,1,* Dongmei Deng,2,* Jianqiu Yang,1 Simeng Liu,3 Qihong Qian,4 Min Chen,1 Shengru Zhou,1 Yujiang Li,5 Min Li1,4 1Department of Dermatology, Dushu Lake Hospital Affiliated to Soochow University (Medical Center of Soochow University, Suzhou Dushu Lake Hospital), Suzhou Ctiy, Jiangsu, People’s Republic of China; 2Health Management Center, The Fifth People’s Hospital of Hainan Province, Haikou Ctiy, Hainan, People’s Republic of China; 3Department of Dermatology, Aerospace Center Hospital, Beijing Ctiy, People’s Republic of China; 4Department of Dermatology, The First Affiliated Hospital of Soochow University, Suzhou Ctiy, Jiangsu, People’s Republic of China; 5Department of Dermatology, Sanmenxia Central Hospital, Sanmenxia Ctiy, Henan, People’s Republic of China*These authors contributed equally to this workCorrespondence: Yujiang Li, Department of Dermatology, Sanmenxia Central Hospital, Middle Road of Yaoshan, Hubin District, Sanmenxia, Henan, 472000, People’s Republic of China, Tel +86-13525857005, Email [email protected] Min Li, Department of Dermatology, the First Affiliated Hospital of Soochow University, No. 188 Shizi Road, Gusu District, Suzhou, Jiangsu, 215006, People’s Republic of China, Tel +86-18936140383, Email [email protected]: 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.Keywords: dyskeratosis congenita, mucocutaneous triad, DKC1 gene, mutation
