P1303A novel TAP2 mutation leading to the absence of HLA class I is responsiblefor a neoplastic degeneration over previous skin lesion

Agustin Espana, MD, Department of Dermatology, University Clinic of Navarra,Pamplona, Navarra, Spain; Oscar De La Calle, PhD, Department of Immunology,San Pablo Hospital, Barcelona, Spain; Laura Martinez, PhD, Department ofImmunology, San Pablo Hospital, Barcelona, Spain; Celia Gonzalez, PhD,Department of Immunology, San Pablo Hospital, Barcelona, Spain

Introduction: Bare lymphocyte syndrome (BLS) is characterized by a severe down-regulation of HLA class I (BLS type I) or class II molecules (BLS type II). To date, 16cases of HLA I class deficiency have been described. Patients with TAP deficienciesare usually characterized by respiratory chronic bacterial infections, and features ofa chronic granulomatous inflammation. Herein, we present a new case of BLS type I,with a novel TAP2 mutation which has not been described previously, associatedwith a neoplastic degeneration over previous skin lesions.

Case report: A 46-year-old female presented with a history of severe bronchiectasisand skin ulcers on the right leg with necrotizing granulomatous lesions since the ageof 10. Tuberculosis and fungus infections were ruled out. An aggressive form ofsquamous cell carcinoma over previous ulcerated skin lesions on right leg wasdeveloped, leading to the right leg amputation. The patient relapsed with liver, lungand bone metastasis, and she died 4 months later. An HLA I class deficiency and HLAII class conserved expression were observed in the patient. The patient washomozygous for all the HLA loci, suggesting consanguinity. Sequencing of the fulllength TAP1 and TAP2 complementary DNAs (cDNA) showed a single pointmutation at nucleotide 628, C to G, placed at exon 3 of the TAP2 gene. Thismutation converts the arginine 210 into a premature stop codon. The relatives (themother and three daughters) were heterozygous for the mutation and the HLAhaplotype.

Discussion: TAP down-regulation in neoplasias has been reported in many studiesand could be related with the emergence of immune escape of tumors. HLA class Ideficient patients usually shown chronic bacterial infections of the respiratory tractand severe chronic cutaneous granulomatous lesions. In this report, we describedfor the first time the development of neoplastic disease over previous TAP-relatedlesions.

AB80

cial support: None identified.

Commer

P1304Dyskeratosis congenita, a case report with late onset bone marrowhypoplasia

Dan R. Lopez-Garcıa, MD, Servicio de Dermatologıa, Hospital Universitario,U.A.N.L., Mty, N.L., Mexico; Claudia I. Ancer-Arellano, Ma. del Carmen Liy Wong,MD, Servicio de Dermatologıa, Hospital Universitario, MTY, N.L., Mexico;Minerva Gomez-Flores, MD, Servicio de Dermatologıa, Hospital Universitario,MTY, N.L., Mexico; Jorge Ocampo-Candiani, MD, Servicio de Dermatologıa,Hospital Universitario, MTY, N.L., Mexico

Background: Dyskeratosis congenita (DC) is a rare disorder characterized by aclassical tetrad of progressive bone marrow failure, reticulated skin hyperpigmen-tation, nail dystrophy, and oral leukoplakia. DC is predominantly inherited in an X-linked recessive form. The gene responsible, DKC1 located at Xq28, encodes for adyskeratin that is believed to be essential in ribosome biogenesis and telomeraseassembly. Early mortality is often associated with bone marrow failure.

Case report: A 29-year-old male, who noted since early infancy the presence of ageneralized skin disorder that affected the scalp, oral mucosa, nails, and skin foldspredominantly. Physical examination revealed a marked mottled and reticulatehyperpigmentation of the face, neck, arms, and legs, sparing the trunk.Poikilodermatous changes with atrophy and telangiectasia in seborrheic regionswas found, along with xerosis scarring alopecic patches on the scalp. Twenty naildystrophy and leukoplakia was noted on the tonge and oral mucosa. The patient hada medical history of moderate tobacco consumption, photosensitivity, and esoph-ageal dilations. A month before the first visit to our department, the patient was seenby a hematologist because of fatigue; the CBC revealed moderate pancytopenia, anda bone marrow biopsy showed hypoplasia. Skin biopsy was compatible withdyskeratosis congenita. The patient was advised to continue close follow-up at thehematology clinic.

Discussion: DC is a rare genodermatosis; approximately 200 cases are reported inthe literature. The vast majority of cases are diagnosed during childhood, and 70% ofpatients die directly from bone marrow failure at a median age of 16 years. Theinteresting features of this case are the late presentation of bone marrow failure andthe delay in diagnosis. Management strategies should include photoprotection,smoking cessation, surveillance of leukoplakia, and close hematologic follow-up.The success rate of BMT is limited because of a high prevalence of fatal pulmonarycomplications which likely reflect preexisting pulmonary disease in these patients.DNA testing of the genes responsible for the X-linked and autosomal dominant formsof DC allows us to perform prenatal testing, early diagnosis via postnatal testing(which may, in turn, enable harvesting of the patient’s bone marrow before marrowfailure), and carrier detection. Gene therapy may be a promising future treatmentmodality for this potentially fatal disease.

cial support: None identified.

Commer

J AM ACAD DERMATOL

P1305Incontinentia pigmenti in three generations: A case report

Elizabeth Clemons, Louisiana State University Health Sciences Center, Shreveport,LA, United States; David Clemons, MD, Dermatology and Skin Surgery,Shreveport, LA, United States; J. Anthony Lee, MD, The Delta Pathology Group,Shreveport, LA, United States; Seth Berney, MD, Louisiana State University HealthSciences Center, Shreveport, LA, United States

Incontinentia pigmenti (IP), also known as BlocheSulzberger syndrome, is a rare, X-linked dominant genodermatosis caused by a mutation of the nuclear factor kappa Bessential modulator (NEMO) gene which is an essential component to manyimmune, inflammatory, and apoptotic pathways. This mutation represents a lethaldefect in the majority of male fetuses; however, it is variably expressed in females.The cutaneous manifestations of IP typically evolve through four successive, yetoverlapping stages: vesiculobullous, veruccous, hyperpigmented, and atrophic.Other commonly affected sites include the eyes, hair, teeth, and central nervoussystem. The major causes of morbidity and mortality are related to neurologic andophthalmologic sequelae including seizures, mental retardation, and visual impair-ment. We describe the case of a 9-day-old female infant who presented with theclassic vesiculobullous skin lesions involving the trunk and extremities. A biopsy ofthe infant’s skin rash revealed eosinophilic spongiosis, vesiculation, and dyskeratotickeratinocytes consistent with IP. Bacterial cultures and herpes simplex PCR of thelesions were negative. Magnetic resonance imaging of the brain was interpreted asfocal gyral edema with peripheral enhancement representative of focal corticalnecrosis. Further questioning of the patient’s mother and maternal grandmotherindicated that they had similar, undiagnosed perinatal skin conditions. Examinationof the patient’s mother demonstrated linear, atrophic skin lesions located predom-inantly over the extremities, and the maternal grandmother was found to havepersistent brown macules in her axillae in addition to abnormal dentition alsoconsistent with IP. The patient later experienced developmental delays and a seizuredisorder. This case illustrates in three successive generations the various physicalfindings at different stages of the rare genetic disease of IP.

cial support: None identified.

Commer

P1306Palmoplantar keratoderma in a patient with a chromosome 12q deletion

Ronald Vender, MD, Dermatrials Research, Hamilton, ON, Canada; IanMacDougall, Michael C. DeGroote School of Medicine, Hamilton, ON, Canada

Keratins are a group of proteins that form the intermediate filament cytoskeletonthat is essential in providing structural integrity to the skin. These proteins can bebroadly classified into type I and type II keratins, which are encoded on two denseclusters on chromosome 17q and 12q, respectively. Disruptions of these genes mayresult in a heterogeneous group of diseases characterized by marked thickening ofthe epidermis of the palms and soles. Past reports have described patients withdeletions, translocations and ring formation of chromosome 12. We report the caseof a 9-year-old boy with a de novo interstitial deletion of the long arm of chromosome12: 46,XY,del(12)(Q24.31Q24.33) presenting with palmoplantar keratoderma.

cial support: None identified.

Commer

FEBRUARY 2008