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Pediatr Blood Cancer 2021 Jun 4:e29177. Epub 2021 Jun 4.

Department of Bone Marrow Transplantation and Cellular Therapy, St. Jude Children's Research Hospital, Memphis, Tennessee.

Background: Bone marrow failure in dyskeratosis congenita (DKC) is progressive, and allogeneic hematopoietic cell transplantation (HCT) is the only curative treatment. However, outcomes after HCT are suboptimal because of mucosal, vascular, pulmonary, and hepatic fragility, which can be exacerbated by chemotherapy conditioning and graft-versus-host disease (GVHD). These toxicities can be mitigated by reducing the intensity of the conditioning regimen. Read More

J Pak Med Assoc 2021 Mar;71(3):1007-1010

Foundation University Medical College, Rawalpindi, Pakistan.

Dyskeratosis congenita is a very rare inherited haematological disorder characterised by a classical clinical triad of leukoplakia, skin pigmentation and dystrophied nails. Here is a case of a young patient who presented with brittle nails, lacy hyperpigmentation of the skin and leukoplakia along with pancytopenia. Haematopoietic stem cell transplantation is the only cure for this disease but due to financial constraints of the family it was not possible. Read More

Case Rep Ophthalmol 2021 May-Aug;12(2):344-349. Epub 2021 May 7.

Department of Ophthalmology, Osaka Medical College, Takatsuki-City, Japan.

Dyskeratosis congenita (DKC) is a rare, multisystem, bone marrow failure disease characterized by abnormalities such as in the skin, mucosa, nervous system, and lungs. Here we report a rare case of presumed DKC causing total retinal detachment in the right eye and severe peripheral retinal vascular occlusion in the left eye. A 3-year-old boy was presented with vitreous hemorrhage and total retinal detachment in the right eye and was scheduled to undergo vitreous surgery in the right eye and detailed ophthalmologic examination of the left eye under general anesthesia. Read More

Br J Haematol 2021 Jun 21;193(6):1238-1246. Epub 2021 May 21.

National Institute of Neurological Disorders and Stroke, Bethesda, MD, USA.

Reproductive health may be adversely impacted in women with dyskeratosis congenita (DC) and related telomere biology disorders (TBD). We evaluated gynaecological problems, fertility, and pregnancy outcomes in 39 females aged 10-81 years who were followed longitudinally in our DC/TBD cohort. Twenty-six had bone marrow failure and 12 underwent haematopoietic cell transplantation. Read More

BMJ Case Rep 2021 May 11;14(5). Epub 2021 May 11.

Head and Neck Department, Operative Unit of Maxillo-Facial Surgery and Otolaryngology, IRCCS Ospedale Casa Sollievo della Sofferenza, San Giovanni Rotondo, Puglia, Italy

Dyskeratosis congenita is a rare disease caused by telomerase dysfunction classically characterised by the triad: skin pigmentation, nail dystrophy and mucosal leukoplakia. Few cases are described in literature regarding patients with head and neck squamous cell carcinoma affected by dyskeratosis congenita, and the therapeutic decisions are not yet well defined. A review of the literature of the last 20 years (2001-2021) was performed, and it was analysed the case of a 38-year-old male patient affected by dyskeratosis congenita diagnosed with a squamous cell carcinoma of the inferior alveolar ridge, treated with surgery. Read More

Life Sci 2021 Jul 1;277:119556. Epub 2021 May 1.

Department of Biochemistry & Biophysics, University of Kalyani, Kalyani 741235, India. Electronic address:

Objective: Poly(ADP-ribose) polymerase1 (PARP1) interacts and poly(ADP-ribosyl)ates telomere repeat binding factor 2 (TRF2), which acts as a platform to recruit a large number of proteins at the telomere. Since the discovery of TRF2-SLX4 interaction, SLX4 is becoming the key player in telomere length (TL) maintenance and repair by telomere sister chromatid exchange (T-SCE). Defective TL maintenance pathway results in a spectrum of diseases called telomeropathies like dyskeratosis congenita, aplastic anemia, fanconi anemia, cancer. Read More

Front Cell Dev Biol 2021 16;9:649328. Epub 2021 Apr 16.

Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Sciences, Peking Union Medical College, Tianjin, China.

CTC1 is a component of the mammalian CST (CTC1-STN1-TEN1) complex which plays essential roles in resolving replication problems to facilitate telomeric DNA and genomic DNA replication. We previously reported that the depletion of CTC1 leads to stalled replication fork restart defects. Moreover, the mutation in CTC1 caused cancer-prone diseases including Coats plus (CP) or dyskeratosis congenita (DC). Read More

JBJS Case Connect 2021 Apr 21;11(2):e20.00486. Epub 2021 Apr 21.

Rady Children's Hospital San Diego, Division of Orthopaedic Surgery, San Diego, California.

Case: A 14-year-old boy with dyskeratosis congenita (DKC), status-post unrelated bone marrow transplant (BMT), sustained a femoral shaft fracture. Despite immediate fixation with the widest possible titanium elastic nails, fixation construct rigidity was insufficient and malunion occurred with refracture 5 years later. Revision fixation with rigid intramedullary nailing has maintained position for 1 year, although callus formation remains meager. Read More

BMC Bioinformatics 2021 Apr 14;22(1):190. Epub 2021 Apr 14.

Unité Récepteurs-Canaux, Institut Pasteur, 75015, Paris, France.

Background: Harmonin Homogy Domains (HHD) are recently identified orphan domains of about 70 residues folded in a compact five alpha-helix bundle that proved to be versatile in terms of function, allowing for direct binding to a partner as well as regulating the affinity and specificity of adjacent domains for their own targets. Adding their small size and rather simple fold, HHDs appear as convenient modules to regulate protein-protein interactions in various biological contexts. Surprisingly, only nine HHDs have been detected in six proteins, mainly expressed in sensory neurons. Read More

Front Microbiol 2021 11;12:654370. Epub 2021 Mar 11.

Department of Chemistry and Biochemistry, Alberta RNA Research and Training Institute, University of Lethbridge, Lethbridge, AB, Canada.

During ribosome synthesis, ribosomal RNA is modified through the formation of many pseudouridines and methylations which contribute to ribosome function across all domains of life. In archaea and eukaryotes, pseudouridylation of rRNA is catalyzed by H/ACA small ribonucleoproteins (sRNPs) utilizing different H/ACA guide RNAs to identify target uridines for modification. H/ACA sRNPs are conserved in archaea and eukaryotes, as they share a common general architecture and function, but there are also several notable differences between archaeal and eukaryotic H/ACA sRNPs. Read More

Mol Med Rep 2021 May 24;23(5). Epub 2021 Mar 24.

Department of Emergency, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou, Zhejiang 310006, P.R. China.

Sepsis‑induced cardiorenal syndrome is one of the multiple organ dysfunctions observed in sepsis. It is determined by a primary dysfunction in one organ that leads to secondary injury to another organ. Studies have shown the involvement of microRNAs (miRs) in the diagnosis and prognosis of several pathologies. Read More

Ann Thorac Surg 2021 Mar 19. Epub 2021 Mar 19.

Department of Thoracic Surgery, Kyoto University Hospital. Electronic address:

We report the first two dyskeratosis congenita (DKC) cases, involving progressive pulmonary diseases, requiring urgent living-donor lung transplantations. Case 1: A 13-year-old boy with DKC underwent bone marrow transplantation for aplastic anemia at age of 6. He developed severe pulmonary right-to-left shunting and fibrosis. Read More

Int J Dermatol 2021 Mar 19. Epub 2021 Mar 19.

Department of Dermatology and Venereology, Faculty of Medicine, Public Health, and Nursing, Universitas Gadjah Mada, Yogyakarta, Indonesia.

Poikiloderma is a skin condition that combines atrophy, telangiectasia, and macular pigment changes (hypo- as well as hyperpigmentation). It is often mistaken for mottled pigmentation by general practitioners or nondermatology specialists. Poikiloderma can be a key presenting symptom of Rothmund-Thomson syndrome (RTS), dyskeratosis congenita (DC), hereditary sclerosing poikiloderma (HSP), hereditary fibrosing poikiloderma with tendon contractures, myopathy, and pulmonary fibrosis (POIKTMP), xeroderma pigmentosum (XP), Bloom syndrome (BS), Kindler syndrome (KS), and Clericuzio-type poikiloderma with neutropenia (PN). Read More

Int J Oral Maxillofac Surg 2021 Mar 15. Epub 2021 Mar 15.

Department of Otolaryngology-Head and Neck Surgery, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea. Electronic address:

Dyskeratosis congenita is a rare inherited bone marrow failure syndrome with three distinct clinical features: nail dystrophy, reticular skin pigmentation, and oral leukoplakia. The case of a 5-year-old female patient diagnosed with squamous cell carcinoma of the tongue is reported here. An autosomal dominant type 3 TINF2 mutation subsequently confirmed the diagnosis of dyskeratosis congenita. Read More

Brain Behav 2021 May 18;11(5):e02079. Epub 2021 Mar 18.

Department of Radiology, Guangzhou Women and Children's Medical Center, Guangzhou, China.

Objective: This study aimed to summarize the magnetic resonance imaging (MRI) and computed tomography (CT) features of the central nervous system (CNS) in children with Hoyeraal-Hreidarsson syndrome.

Methods: The imaging and clinical data of four children diagnosed with Hoyeraal-Hreidarsson syndrome by clinical and laboratory tests in the Guangzhou Women and Children's Medical Center were gathered and analyzed retrospectively. The clinical manifestations and CNS imaging features of Hoyeraal-Hreidarsson syndrome were summarized based on our results and a literature review. Read More

Hum Genet 2021 Jun 11;140(6):945-955. Epub 2021 Mar 11.

Division of Cancer and Genetics, School of Medicine, Cardiff University, Heath Park, Cardiff, CF14 4XN, UK.

Telomere biology disorders are complex clinical conditions that arise due to mutations in genes required for telomere maintenance. Telomere length has been utilised as part of the diagnostic work-up of patients with these diseases; here, we have tested the utility of high-throughput STELA (HT-STELA) for this purpose. HT-STELA was applied to a cohort of unaffected individuals (n = 171) and a retrospective cohort of mutation carriers (n = 172). Read More

Cell Mol Life Sci 2021 May 18;78(9):4235-4257. Epub 2021 Feb 18.

Division of Cancer Genetics and Therapeutics, Laboratory of NFκB Signaling, Institute of Molecular and Cell Biology (IMCB), A*STAR (Agency for Science, Technology and Research), Proteos, 61, Biopolis Drive, Singapore, 138673, Singapore.

Reactivation of telomerase is a major hallmark observed in 90% of all cancers. Yet paradoxically, enhanced telomerase activity does not correlate with telomere length and cancers often possess short telomeres; suggestive of supplementary non-canonical roles that telomerase might play in the development of cancer. Moreover, studies have shown that aberrant expression of shelterin proteins coupled with their release from shortening telomeres can further promote cancer by mechanisms independent of their telomeric role. Read More

Mol Cell Biol 2021 03 24;41(4). Epub 2021 Mar 24.

Lady Davis Institute for Medical Research, Jewish General Hospital, McGill University, Montréal, Quebec, Canada

The nuclear and subnuclear compartmentalization of the telomerase-associated protein and H/ACA ribonucleoprotein component dyskerin is an important although incompletely understood aspect of H/ACA ribonucleoprotein function. Four SUMOylation sites were previously identified in the C-terminal nuclear/nucleolar localization signal (N/NoLS) of dyskerin. We found that a cytoplasmic localized C-terminal truncation variant of dyskerin lacking most of the C-terminal N/NoLS represents an under-SUMOylated variant of dyskerin compared to wild-type dyskerin. Read More

Stem Cell Res Ther 2021 Jan 29;12(1):92. Epub 2021 Jan 29.

Division of Hematopoietic Innovative Therapies, Centro de Investigaciones Energéticas Medioambientales y Tecnológicas (CIEMAT), Avenida Complutense, 40, 28040, Madrid, Spain.

Dyskeratosis congenita (DC) is a rare telomere biology disorder, which results in different clinical manifestations, including severe bone marrow failure. To date, the only curative treatment for the bone marrow failure in DC patients is allogeneic hematopoietic stem cell transplantation. However, due to the toxicity associated to this treatment, improved therapies are recommended for DC patients. Read More

Hematology 2021 Dec;26(1):134-143

Department of Bone Marrow Transplantation, Hebei Yanda Lu Daopei Hospital, Langfang, People's Republic of China.

: The outcomes of alternative donor hematopoietic stem cell transplantation (HSCT) with unmanipulated grafts for Inherited bone marrow failure syndromes (IBMFS) are discouraging. Our study is to demonstrate that IBMFS with disease-specific characteristics requires a tailored conditioning regimens to enhance engraftment and reduce regimen related toxicities. : We retrospectively analyzed 42 patients diagnosed with IBMFS and transplanted with an alternative donor graft at our center from November 2012 to August 2018. Read More

J Biol Chem 2020 Nov 22;296:100064. Epub 2020 Nov 22.

Department of Molecular, Cellular, and Developmental Biology, University of Michigan, Ann Arbor, Michigan, USA. Electronic address:

Genetic mutations that affect telomerase function or telomere maintenance result in a variety of diseases collectively called telomeropathies. This wide spectrum of disorders, which include dyskeratosis congenita, pulmonary fibrosis, and aplastic anemia, is characterized by severely short telomeres, often resulting in hematopoietic stem cell failure in the most severe cases. Recent work has focused on understanding the molecular basis of these diseases. Read More

Rev Chil Pediatr 2020 Aug 11;91(4):545-552. Epub 2020 Sep 11.

Servicio de Hemato-Oncología Pediátrica y Trasplante de Médula Ósea, Fundación Valle del Lili, Cali, Colombia.

Introduction: Bone marrow failure (BMF) syndromes are rare disorders with an annual incidence of 2-4 cases per million. Treatment options include immunosuppressive therapy (IST) and hematopoietic stem cell transplantation (HSCT).

Objective: To analyze the outcomes of pediatric patients diagnosed with BMF treated in a tertiary care center. Read More

Autops Case Rep 2020 Sep 2;10(3):e2020203. Epub 2020 Sep 2.

State University of New York, Upstate Medical University, Department of Pathology, Syracuse, NY, USA.

Dyskeratosis congenita (DC) is a genetic syndrome with progressive multisystem involvement classically characterized by the clinical triad of oral leukoplakia, nail dystrophy, and reticular hyperpigmentation. Frequent complications are bone marrow failure, increased rate of malignancy, lung and liver diseases. DC results from an anomalous progressive shortening of telomeres resulting in DNA replication problems inducing replicative senescence. Read More

Hematology Am Soc Hematol Educ Program 2020 12;2020(1):107-114

Division of Bone Marrow Transplantation, General Hospital of the Federal University of Parana, Curitiba, Brazil.

Advances in the diagnosis and treatment of inherited bone marrow failure syndromes (IBMFS) have provided insight into the complexity of these diseases. The diseases are heterogeneous and characterized by developmental abnormalities, progressive marrow failure, and predisposition to cancer. A correct diagnosis allows for appropriate treatment, genetic counseling, and cancer surveillance. Read More

Exp Clin Transplant 2020 Nov 27. Epub 2020 Nov 27.

From the Division of Transplant Surgery, Department of Surgery, Ohio State University Wexner Medical Center, Columbus, Ohio, USA.

Dyskeratosis congenita, a rare genetic disorder typified by progressive bone marrow failure, is classically characterized by the triad of abnormal skin pigmentation, nail dystrophy, and oral leukoplakia; however, it is a multisystem disease. Although hepatic involvement occurs in about 7% of patients with dyskeratosis congenita, end-stage liver disease is rare. Treatment of dyskeratosis congenita generally involves hematopoietic stem cell transplant. Read More

Cancers (Basel) 2020 Nov 25;12(12). Epub 2020 Nov 25.

Department of Experimental, Diagnostic and Specialty Medicine, University of Bologna, Via Massarenti 9, 40138 Bologna, Italy.

Dyskerin is a nucleolar protein involved in the small nucleolar RNA (snoRNA)-guided pseudouridylation of specific uridines on ribosomal RNA (rRNA), and in the stabilization of the telomerase RNA component (hTR). Loss of function mutations in DKC1 causes X-linked dyskeratosis congenita, which is characterized by a failure of proliferating tissues and increased susceptibility to cancer. However, several tumors show dyskerin overexpression. Read More

Osteoporos Int 2021 Jun 27;32(6):1227-1231. Epub 2020 Nov 27.

Center of Medical Genetics, University of Antwerp, Antwerp, Belgium.

We report a case of a young male patient with clinical signs of dyskeratosis congenita who presented with multiple bilateral low-traumatic hip fractures. Whole exome sequencing (WES) showed a previously unreported mutation in the poly(A)-specific ribonuclease (PARN) gene. Zoledronic acid 5 mg over 3 years was effective at preventing further fractures. Read More

Pediatr Clin North Am 2021 02;68(1):261-276

Hackensack Meridian School of Medicine, Nutley, NJ 07110, USA.

Systemic diseases often manifest with cutaneous findings. Many pediatric conditions with prominent skin findings also have significant pulmonary manifestations. These conditions include both inherited multisystem genetic disorders such as yellow-nail syndrome, neurofibromatosis type 1, tuberous sclerosis complex, hereditary hemorrhagic telangiectasia, Klippel-Trénaunay-Weber syndrome, cutis laxa, Ehlers-Danlos syndrome, dyskeratosis congenita, reactive processes such as mastocytosis, and aquagenic wrinkling of the palms. Read More

Cureus 2020 Oct 13;12(10):e10933. Epub 2020 Oct 13.

Department of Cornea, Anand Eye Institute, Hyderabad, IND.

Purpose: To report a case of partial limbal stem cell deficiency and characteristic mucocutaneous triad in an 11-year-old boy.

Methods: Systemic features along with ocular features are described in this case report.

Results: Ophthalmic evaluation showed bilateral partial limbal stem cell deficiency (LSCD) and systemic examination revealed characteristic mucocutaneous triad of oral leukoplakia, skin hypopigmentation, and nail dystrophy suggestive of the Zinsser-Engman-Cole syndrome or dyskeratosis congenita. Read More

Intern Med 2021 Apr 16;60(8):1257-1263. Epub 2020 Nov 16.

Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Japan.

A 42-year-old man with a history of surgery for tongue cancer was referred to our hospital due to an abnormal chest shadow. High-resolution computed tomography showed lower lobe reticulation. A physical examination revealed nail dystrophy, oral leukoplakia, and reticulated hypopigmentation. Read More