1/8. dyskeratosis congenita: an autosomal recessive variant.We describe a woman with dyskeratosis congenita (DKC), microcephaly, and a purple discoloration of the tongue. The latter findings are not commonly described in males with DKC, have been reported in another female patient with this condition, and may represent the phenotype of an autosomal recessive entity of DKC. Results of x chromosome inactivation studies did not support X-linked DKC in our family. The additional findings of an affected brother and parental consanguinity support the hypothesis of autosomal recessive inheritance.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
2/8. Oral carcinoma in a young man: a case of dyskeratosis congenita.We report a 28-year-old male with a voluminous growth of the tongue, present for 6 months. The histological examination revealed a squamous cell carcinoma. The patient was also affected by oral leukoplakia, nail dystrophy, reticulated poikiloderma of the neck and hyperkeratosis of palms and soles. On the basis of clinical features and histological findings, as well as findings from the family, the diagnosis of dyskeratosis congenita (DKC) was made.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
3/8. A novel missense mutation in the DKC1 gene in a Japanese family with X-linked dyskeratosis congenita.The authors report 2 male patients with dyskeratosis congenita (DC) in a Japanese kindred. Sequencing of the complementary dna of the dyskerin gene (DKC1) revealed a T-to-C transition at nucleotide 1285 in exon 12 that resulted in a novel missense mutation L398P. Despite harboring the same mutation in the DKC1 gene, one patient had significantly milder hematological symptoms than the other, indicating that there may be other factors that determine the severity of DC.- - - - - - - - - - ranking = 4keywords = family (Clic here for more details about this article) |
4/8. DKC1 gene mutation in a Taiwanese kindred with X-linked dyskeratosis congenita.dyskeratosis congenita (DKC) is a rare inherited disease characterized by the triad of abnormal skin pigmentation, nail dystrophy, and mucosal leukoplakia. Recent studies demonstrated mutations in the DKC1 gene encoding a protein named dyskerin, which is a component of human telomerase. In addition to the hypothesized function of pseudouridination in rRNA biosynthesis, ribosomal subunit assembly, and/or centromere/ microtubule binding, lower levels of telomerase activity in cells from patients with X-linked DKC have been observed. We report the mutation analysis of a Taiwanese family with X-linked DKC. The patient was a 19-year-old man who presented with progressive reticulate hyperpigmentation, nail dystrophy, alopecia, leukoplakia of the tongue, and pancytopenia. He died of enterocolitis and escherichia coli sepsis at the age of 20 years. Only his mother's dna was available for mutation analysis, which revealed a nucleotide transition of C to T (1058 C --> T), a hotspot mutation in DKC, resulting in an amino acid change from alanine to valine (A353V) in the DKC1 gene. Recent advances in the research of telomerase and its implications in the human aging process and cancer are discussed.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
5/8. Late presentation of dyskeratosis congenita as apparently acquired aplastic anaemia due to mutations in telomerase rna.Aplastic anaemia in adults is usually acquired, but rarely constitutional types of bone marrow failure can occur late in life. We assessed two families with onset of pancytopenia in adults and detected two novel point mutations in the telomerase rna gene (TERC) in each family. This gene is abnormal in some kindreds with dyskeratosis congenita. Individuals in our families with mutated TERC did not have physical signs of dyskeratosis congenita, and their blood counts were nearly normal, but all had severely shortened telomeres, reduced haemopoietic function, and raised serum erythropoietin and thrombopoietin. bone marrow failure of variable severity due to dyskeratosis congenita, historically characterised by associated physical anomalies and early pancytopenia, may be present in otherwise phenotypically normal adults, and can masquerade as acquired aplastic anaemia.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
6/8. Coats' plus: a progressive familial syndrome of bilateral Coats' disease, characteristic cerebral calcification, leukoencephalopathy, slow pre- and post-natal linear growth and defects of bone marrow and integument.In 1988 we reported two sisters with bilateral Coats' disease, sparse hair, dystrophic nails, and primeval splashes of intracranial calcification. We now provide an update on this family documenting the occurrence of skeletal defects comprising abnormal bone marrow, osteopenia, and sclerosis with a tendency to fractures, a mixed cerebellar and extrapyramidal movement disorder, infrequent epileptic seizures, leukodystrophic changes, and postnatal growth failure. Additionally, we present two previously unreported individuals from ireland and switzerland with the identical disorder which we designate Coats' plus. Since our original publication a number of other authors have described, frequently as a "new" syndrome, cases with a variable combination of the same features observed in our patients. We review this literature and suggest that the phenotypic overlap with dyskeratosis congenita may provide a clue to the molecular aetiology of this multisystem disorder.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
7/8. The longest surviving child with Hoyeraal-Hreidarsson syndrome.We describe the case of a 12-year old boy with Hoyeraal-Hreidarsson syndrome (HHS). This syndrome includes intrauterine growth retardation, microcephaly, mental retardation, cerebellar malformation, and pancytopenia. HHS is a severe multisystem disorder associated with premature mortality, due to bone marrow failure. The pathogenesis and genetic basis presently is unknown. Onset of HHS has only been described in boys and reporters speculated that HHS may be a severe form of X-linked dyskeratosis congenita (DKC). In this paper, we reported an autosomal recessive form of HHS in a family. Almost all cases have died before 4 years (except one at 7 years) our patient is alive at his 12th year at all, probably because of autosomal recessive gene transmission.- - - - - - - - - - ranking = 1keywords = family (Clic here for more details about this article) |
8/8. Identification and functional characterization of 2 variant alleles of the telomerase rna template gene (TERC) in a patient with dyskeratosis congenita.Heterozygous mutations of the human telomerase rna template gene (TERC) have been described in patients with acquired aplastic anemia and the autosomal dominant form of dyskeratosis congenita (DKC). patients with mutations in both TERC alleles have not yet been reported. Here, we report a patient with DKC who inherited 2 distinct TERC sequence variants from her parents; a deletion (216_229del) in one and a point mutation (37A>G) in the other allele of the TERC gene. Her marrow was hypocellular and showed an abnormal clone [46, XX t(7;21)(q34;q22)]. The telomere lengths in leukocytes of the patient and her relatives were shorter than those of the age-matched controls and were progressively shorter in subsequent generations of family members with the 216_229del allele. telomerase enzymatic levels in lymphocytes from the patient were approximately half of those measured in healthy controls. The 216_229del mutation failed to reconstitute telomerase activity in transfected cells, but, when coexpressed with the 37A>G variant, telomerase activity was only modestly suppressed. These clinical and laboratory findings support the concept that telomerase levels in human hematopoietic stem cells are tightly controlled as even moderately reduced levels result in accelerated telomere shortening and eventual marrow failure.- - - - - - - - - - ranking = 1.0163084523734keywords = family, member (Clic here for more details about this article) |