BACKGROUND Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia,nail dystrophy,and abnormal skin pigmentation.The genetics of dyskeratosis congenita in...BACKGROUND Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia,nail dystrophy,and abnormal skin pigmentation.The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance,including TINF2.CASE SUMMARY Here,we report a female patient who presented thrombocytopenia,anemia,reticulate hyperpigmentation,dystrophy in fingernails and toenails,and leukoplakia on the tongue.A histopathological study of the skin showed dyskeratocytes;however,a bone marrow biopsy revealed normal cell morphology.The patient was diagnosed with dyskeratosis congenita,but her family history did not reveal significant antecedents.Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene,namely,NM_001099274.1:-c.854delp.(Val285-Alafs*32).An analysis of telomere length showed short telomeres relative to the patient’s age.CONCLUSION The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.展开更多
Portal hypertension(PH)refers to a collection of syndromes characterized by an increase in pressure within the portal venous system and/or elevated portal venous blood flow,most commonly caused by cirrhosis.This condi...Portal hypertension(PH)refers to a collection of syndromes characterized by an increase in pressure within the portal venous system and/or elevated portal venous blood flow,most commonly caused by cirrhosis.This condition is frequently associated with viral hepatitis and chronic alcohol abuse,and its complications,such as ascites,hepatic encephalopathy,and esophageal varices,have a considerable impact on mortality.Dyskeratosis congenita(DC)is a rare genetic disorder that affects multiple systems,most notably manifesting as dystrophy of the fingernails and toenails,skin pigmentation,and mucosal leukoplakia.While cirrhotic PH is an uncommon complication of DC,we present a case of a young patient who presented with PH and had no history of hepatitis or heavy alcohol use.The patient underwent splenectomy and devascularization to treat hypersplenism and esophagogastric varices caused by PH but developed portal vein thrombosis following the surgery.Given the patient's cutaneous manifestations and cirrhosis that could not be attributed to common causes,we continued to search for the underlying cause of PH until the diagnosis of DC was finally made.The patient was subsequently treated with carvedilol to prevent variceal rebleeding and showed no significant complications or bleeding during follow-up.展开更多
Dyskeratosis congenita (DC) is a severe inherited disease characterized by a triad of clinical manifestations including abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. 1 Bone marrow failure is th...Dyskeratosis congenita (DC) is a severe inherited disease characterized by a triad of clinical manifestations including abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. 1 Bone marrow failure is the principal cause of early mortality, together with an increased predisposition to malignancy and fatal pulmonary complications. According to the dyskeratosis congenita registry, a peripheral blood cytopenia of one or more lineages is reported in 93% of patients, with 51% developing pancytopenia before the age of 10 years. 2 In patients with DC, bone marrow failure or bone marrow failure treatment-associated complications account for 67% of total mortality. 3 Therefore, management of bone marrow failure syndrome is crucial in patients with DC.展开更多
Recent advances in reprograming somatic cells from normal and diseased tissues into induced pluripotent stem cells (iPSCs) provide exciting possibilities for generating renewed tissues for disease modeling and therapy...Recent advances in reprograming somatic cells from normal and diseased tissues into induced pluripotent stem cells (iPSCs) provide exciting possibilities for generating renewed tissues for disease modeling and therapy. However, questions remain on whether iPSCs still retain certain markers (e.g. aging) of the original somatic cells that could limit their replicative potential and utility. A reliable biological marker for measuring cellular aging is telomere length, which is maintained by a specialized form of cellular polymerase known as telomerase. Telomerase is composed of the cellular reverse transcriptase protein, the integral RNA component, and other cellular proteins (e.g. dyskerin). Mutations in any of these components of telomerase can lead to a severe form of marrow def iciency known as dyskeratosis congenita (DC). This review summarizes recent f indings on the effect of cellular reprograming via iPS of normal or DC patient-derived tissues on telomerase function and consequently on telomere length maintenance. The potentials and challenges of using iPSCs in a clinical setting will also be discussed.展开更多
Both dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson Syndrome (HHS) are rare inherited bone marrow failure conditions. HHS is considered to be a variant of DC in which neurological deficits and immunodeficiencies...Both dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson Syndrome (HHS) are rare inherited bone marrow failure conditions. HHS is considered to be a variant of DC in which neurological deficits and immunodeficiencies are also present. We describe a very interesting familial cluster where an invariant point mutation of DKC1 located in the exon 11 is observed in the carrier mother and in two decedent males. The older child developed the classical phenotype of HHS at a very early age. The second affected child remains poorly symptomatic, with only mild haematological changes. Telomere shortening, with different severity, is also present in both cases. This paper discusses the clinical spectrum of inherited BM failure syndromes from the perspective different clinical presentation within a family with a DKC1 mutation.展开更多
文摘BACKGROUND Dyskeratosis congenita is a rare disease characterized by bone marrow failure and a clinical triad of oral leukoplakia,nail dystrophy,and abnormal skin pigmentation.The genetics of dyskeratosis congenita include mutations in genes involved in telomere maintenance,including TINF2.CASE SUMMARY Here,we report a female patient who presented thrombocytopenia,anemia,reticulate hyperpigmentation,dystrophy in fingernails and toenails,and leukoplakia on the tongue.A histopathological study of the skin showed dyskeratocytes;however,a bone marrow biopsy revealed normal cell morphology.The patient was diagnosed with dyskeratosis congenita,but her family history did not reveal significant antecedents.Whole-exome sequencing showed a novel heterozygous punctual mutation in exon 6 from the TINF2 gene,namely,NM_001099274.1:-c.854delp.(Val285-Alafs*32).An analysis of telomere length showed short telomeres relative to the patient’s age.CONCLUSION The disease in this patient was caused by a germline novel mutation of TINF2 in one of her parents.
文摘Portal hypertension(PH)refers to a collection of syndromes characterized by an increase in pressure within the portal venous system and/or elevated portal venous blood flow,most commonly caused by cirrhosis.This condition is frequently associated with viral hepatitis and chronic alcohol abuse,and its complications,such as ascites,hepatic encephalopathy,and esophageal varices,have a considerable impact on mortality.Dyskeratosis congenita(DC)is a rare genetic disorder that affects multiple systems,most notably manifesting as dystrophy of the fingernails and toenails,skin pigmentation,and mucosal leukoplakia.While cirrhotic PH is an uncommon complication of DC,we present a case of a young patient who presented with PH and had no history of hepatitis or heavy alcohol use.The patient underwent splenectomy and devascularization to treat hypersplenism and esophagogastric varices caused by PH but developed portal vein thrombosis following the surgery.Given the patient's cutaneous manifestations and cirrhosis that could not be attributed to common causes,we continued to search for the underlying cause of PH until the diagnosis of DC was finally made.The patient was subsequently treated with carvedilol to prevent variceal rebleeding and showed no significant complications or bleeding during follow-up.
文摘Dyskeratosis congenita (DC) is a severe inherited disease characterized by a triad of clinical manifestations including abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. 1 Bone marrow failure is the principal cause of early mortality, together with an increased predisposition to malignancy and fatal pulmonary complications. According to the dyskeratosis congenita registry, a peripheral blood cytopenia of one or more lineages is reported in 93% of patients, with 51% developing pancytopenia before the age of 10 years. 2 In patients with DC, bone marrow failure or bone marrow failure treatment-associated complications account for 67% of total mortality. 3 Therefore, management of bone marrow failure syndrome is crucial in patients with DC.
基金Supported by A Research Scholar Grant of the American Cancer Society (RSG-06-162-01-GMC)
文摘Recent advances in reprograming somatic cells from normal and diseased tissues into induced pluripotent stem cells (iPSCs) provide exciting possibilities for generating renewed tissues for disease modeling and therapy. However, questions remain on whether iPSCs still retain certain markers (e.g. aging) of the original somatic cells that could limit their replicative potential and utility. A reliable biological marker for measuring cellular aging is telomere length, which is maintained by a specialized form of cellular polymerase known as telomerase. Telomerase is composed of the cellular reverse transcriptase protein, the integral RNA component, and other cellular proteins (e.g. dyskerin). Mutations in any of these components of telomerase can lead to a severe form of marrow def iciency known as dyskeratosis congenita (DC). This review summarizes recent f indings on the effect of cellular reprograming via iPS of normal or DC patient-derived tissues on telomerase function and consequently on telomere length maintenance. The potentials and challenges of using iPSCs in a clinical setting will also be discussed.
文摘Both dyskeratosis congenita (DC) and Hoyeraal-Hreidarsson Syndrome (HHS) are rare inherited bone marrow failure conditions. HHS is considered to be a variant of DC in which neurological deficits and immunodeficiencies are also present. We describe a very interesting familial cluster where an invariant point mutation of DKC1 located in the exon 11 is observed in the carrier mother and in two decedent males. The older child developed the classical phenotype of HHS at a very early age. The second affected child remains poorly symptomatic, with only mild haematological changes. Telomere shortening, with different severity, is also present in both cases. This paper discusses the clinical spectrum of inherited BM failure syndromes from the perspective different clinical presentation within a family with a DKC1 mutation.
