Telomere phenotypes in females with heterozygous mutations in the dyskeratosis congenita 1 (DKC1) gene.

Dyskeratosis congenita (DC) is a telomere-mediated syndrome defined by mucocutaneous features. The X-linked mode of inheritance accounts for half the cases, and is thought to predominantly manifest in childhood as bone marrow failure. We identified two male probands who presented in the fifth decade with idiopathic pulmonary fibrosis and cancer. Their pedigrees displayed consecutively affected generations. Five of six females (83%) manifested mucocutaneous features of DC, and two had wound-healing complications. No mutations in autosomal dominant telomere genes were present, but exome sequencing revealed novel variants in the X-chromosome DKC1 gene that predicted missense mutations in conserved residues, p.Thr49Ser and p.Pro409Arg. Variants segregated with the telomere phenotype, and affected females were heterozygotes, showing skewed X-inactivation. Telomerase RNA levels were compromised in cells from DKC1 mutation carriers, consistent with their pathogenic role. These findings indicate that females with heterozygous DKC1 mutations may be at increased risk for developing penetrant telomere phenotypes that, at times, may be associated with clinical morbidity.

Cutaneous dental sinus tract, a common misdiagnosis: a case report and review of the literature.

Cutaneous sinus tracts of dental origin are often initially misdiagnosed and inappropriately treated because of their uncommon occurrence and the absence of symptoms in approximately half the individuals affected. Patients are often referred with a recurrent or chronic cyst, a furuncle, or an ulcer on the face or neck. Correct diagnosis is based on a high index of suspicion and on radiologic evidence of a periapical root infection. Appropriate treatment results in predictable and rapid healing of these lesions. We present a case report of this common misdiagnosis and a review of the literature with regard to diagnosis and treatment.