BACKGROUNDAcne inversa (AI), also called hidradenitis suppurativa, is a chronic, inflammatory, recurrent skin disease of the hair follicle. Familial AI shows autosomal-dominant inheritance caused by mutations in the γ-secretase genes. This study was aimed to identify the specific mutations in the γ-secretase genes in two Chinese families with AI.

METHODSIn this study, two Chinese families with AI were investigated. All the affected individuals in the two families mainly manifested with multiple comedones, pitted scars, and a few inflammatory nodules on their face, neck, trunk, axilla, buttocks, upper arms, and thighs. Reticulate pigmentation in the flexures areas resembled Dowling-Degos disease clinically and pathologically. In addition, one of the affected individuals developed anal canal squamous cell carcinoma. Molecular mutation analysis of γ-secretase genes including PSENEN, PSEN1, and NCSTN was performed by polymerase chain reaction and direct DNA sequencing.

RESULTSTwo novel mutations of PSENEN gene were identified, including a heterozygous missense mutation c.194T>G (p.L65R) and a splice site mutation c.167-2A>G.

CONCLUSIONSThe identification of the two mutations could expand the spectrum of mutations in the γ-secretase genes underlying AI and provide valuable information for further study of genotype-phenotype correlations.

Amyloid Precursor Protein Secretases ; genetics ; DNA Mutational Analysis ; Female ; Hidradenitis Suppurativa ; diagnosis ; genetics ; Humans ; Hyperpigmentation ; diagnosis ; Male ; Membrane Proteins ; genetics ; Middle Aged ; Mutation ; Pedigree ; Skin Abnormalities ; diagnosis ; Skin Diseases, Genetic ; diagnosis ; Skin Diseases, Papulosquamous ; diagnosis

BACKGROUNDThe dyschromatoses are a group of disorders characterized by simultaneous hyperpigmented macules together with hypopigmented macules. Dyschromatosis universalis hereditaria (DUH) and dyschromatosis symmetrica hereditaria are two major types. While clinical and histological presentations are similar in these two diseases, genetic diagnosis is critical in the differential diagnosis of these entities.

METHODSThree patients initially diagnosed with DUH were included. The gene test was carried out by targeted gene sequencing. All mutations detected on ADAR1 and ABCB6 genes were analyzed according to the frequency in control database, the mutation types, and the published evidence to determine the pathogenicity.

RESULTSFamily pedigree and clinical presentations were reported in 3 patients from two Chinese families. All patients have prominent cutaneous dyschromatoses involving the whole body without systemic complications. Different pathogenic genes in these patients with similar phenotype were identified: One novel mutation on ADAR1 (c. 1325C>G) and one recurrent mutation in ABCB6 (c. 1270T>C), which successfully distinguished two diseases with the similar phenotype.

CONCLUSIONTargeted gene sequencing is an effective tool for genetic diagnosis in pigmentary skin diseases.

ATP-Binding Cassette Transporters ; genetics ; Adenosine Deaminase ; genetics ; Adolescent ; Asian Continental Ancestry Group ; Child ; Diagnosis, Differential ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Pedigree ; Pigmentation Disorders ; congenital ; diagnosis ; genetics ; RNA-Binding Proteins ; genetics ; Skin Diseases, Genetic ; diagnosis ; genetics

Livedoid vasculopathy is a rare chronic relapsing disorder characterised by recurrent painful thrombotic and vasculitic ulcers on the legs. We present the cases of two Indian women with livedoid vasculopathy that were found to be associated with an underlying factor V Leiden heterozygous mutation. There were no other thrombotic manifestations, and livedoid vasculopathy was the sole presenting feature of the factor V Leiden mutation, although this could also be coincidental. Initial treatment with high-dose immunosuppressive therapy was suboptimal, and the addition of pentoxifylline and antiplatelet therapy was crucial in achieving disease control and remission. These cases highlight the possible association with an underlying prothrombotic disorder, such as factor V Leiden mutation, in patients with livedoid vasculopathy. Although this association is relatively uncommon, it is more relevant to Indian patients, as the presence of factor V Leiden mutation is highest in this ethnicity as compared to the local Malay and Chinese populations.
Adult ; Blood Vessels ; pathology ; DNA ; genetics ; Factor V ; genetics ; metabolism ; Female ; Humans ; Leg Ulcer ; blood ; genetics ; pathology ; Livedo Reticularis ; blood ; diagnosis ; genetics ; Point Mutation ; Polymerase Chain Reaction ; Skin ; blood supply ; Skin Diseases, Vascular ; blood ; genetics ; pathology

Birt-Hogg-Dube syndrome (BHDS) is an autosomal dominant genodermatosis characterized by cutaneous hair follicle tumors (fibrofolliculoma or trichodiscoma), pulmonary cysts, and increased risk of renal neoplasia. The genetic alteration for BHDS has been mapped to chromosome 17p12q11, and the gene in this region has been cloned and believed to be responsible for the BHDS. Mutations in the BHD gene (also known as FLCN) have been described in the patients with BHDS. We present a case of a 30-yr-old Korean woman with multiple mildly pruritic papules on her face and neck area. The patient had several firm, flesh-colored, dome-shaped, papular lesions measuring between 2 to 5 mm. Except for a history of pneumothorax her medical records were not remarkable. Mutation analysis of the BHD gene was performed, and a novel deletion mutation (p.F519LfsX17 [c.1557delT]) causing truncation of the gene product, folliculin, was found in the exon 14. The actual incidence of BHDS is unknown, but it is most likely underdiagnosed. So it is imperative that doctors recognize the skin lesions of BHDS and institute proper screening to detect other manifestations of the disease. Here, we report a case of BHDS with a novel mutation, which is the first report in Korea.
Adult ; Biopsy ; DNA Mutational Analysis ; Diagnosis, Differential ; Estrone/biosynthesis ; Exons ; Female ; Gene Deletion ; Genetic Predisposition to Disease ; Humans ; Kidney Neoplasms/genetics ; Models, Genetic ; Mutation ; Skin Diseases/diagnosis/*genetics ; Syndrome

BACKGROUNDNontuberculous mycobacterium (NTM) had been reported to cause cutaneous infections which are difficult to interpret due to the variability of the clinical manifestations. Among NTM infections, Mycobacterium marinum (M. marinum) are mostly seen to cause skin infection. It is therefore important to establish a rapid approach for detection and identification of M. marinum from lesions of patients with suspected M. marinum infections.

METHODSSpecimens were obtained from 5 patients with swimming pool granuloma. DNA was extracted and polymerase chain reaction (PCR) was performed. PCR products were digested with Hae III and BstE II, then analysed by pattern restriction analysis to detect heat shock protein (hsp) 65 kD gene.

RESULTSThe 65 kD hsp gene was found in all specimens from patients with swimming pool granuloma. PCR restriction analysis (PRA) identified all 5 samples to be M. marinum infections, and the result was consistent with that of routine bacteriological identification. The lesions subsided or markedly improved upon treatment.

CONCLUSIONSPRA is a sensitive, specific and rapid method in identification of mycobacteria. Application of this method will be helpful for early diagnosis of mycobacterial skin infections.

Adolescent ; Adult ; Bacterial Proteins ; genetics ; Chaperonin 60 ; Chaperonins ; genetics ; Female ; Granuloma ; microbiology ; Humans ; Male ; Mycobacterium marinum ; genetics ; isolation & purification ; Polymerase Chain Reaction ; methods ; Skin Diseases, Bacterial ; diagnosis ; Staining and Labeling ; Swimming Pools

OBJECTIVETo explore clinical, radiographical and genetic characteristics of classical Hutchinson-Gilford progeria syndrome (HGPS).

METHODData of a case of HGPS diagnosed at Tongji Hospital Affiliated to Tongji Medical College of Huazhong University of Science and Technology was analyzed and related literature was reviewed.

RESULTAt the age of 8 months, the affected-infant presented with characteristic manifestation such as short stature, low weight, frontal bossing, alopecia, prominent scalp veins, micrognathia with a vertical midline groove in the chin, sclerodermatous skin, knee joints contracture with a horse-riding stance, and limited range of movement of ankle joints. Blood test showed blood platelet count (416-490) ×10(9)/L. Lower extremities MRI showed reduced subcutaneous fat. LMNA gene analysis showed that the affected-infant carried typical heterozygous mutation: c. 1824C>T (p. G608G), while his parents were normal. At the age of 13 months, X-rays showed short distal phalanges and clavicles with acro-osteolysis. After following up for 15 months, his appearance of progeria became more apparent. As far as we know, there are only 2 cases of classical HGPS confirmed by gene analysis in China.

CONCLUSIONClassical HGPS should be considered when infants appeared with sclerodermatous skin. Genetic analysis could help to diagnose classical HGPS as early as possible and avoid unnecessary investigations. In addition, affected-infants need to be long term followed-up and provided genetic counseling.

Abnormalities, Multiple ; diagnosis ; pathology ; DNA Mutational Analysis ; Diagnosis, Differential ; Hand ; diagnostic imaging ; pathology ; Humans ; Infant ; Lamin Type A ; genetics ; Lower Extremity ; diagnostic imaging ; pathology ; Male ; Mutation ; genetics ; Osteolysis, Essential ; pathology ; Progeria ; diagnosis ; genetics ; pathology ; Retrospective Studies ; Skin Diseases ; diagnosis ; genetics ; pathology ; Tomography, X-Ray Computed

From 2006 to 2010, hospitals in Hanoi treated 10 human patients for dirofilariasis. The worms were collected from parasitic places, and identification of the species was completed by morphology and molecular methods. Ten parasites were recovered either from the conjunctiva (n=9) or subcutaneous tissue (n=1). The parasites were 4.0-12.5 cm in length and 0.5-0.6 mm in width. Morphological observations suggested all parasites as Dirofilaria repens. Three of the 10 parasites (1 from subcutaneous tissue and 2 from eyes) were used for molecular confirmation of the species identification. A portion of the mitochondrial cox1 (461 bp) was amplified and sequenced. Nucleotide and amino acid homologies were 95% and 99-100%, respectively, when compared with D. repens (Italian origin, GenBank AJ271614; DQ358814). This is the first report of eye dirofilariasis and the second report of subcutaneous tissue dirofilariasis due to D. repens in Vietnam.
Adult ; Aged ; Animals ; Cyclooxygenase 1/genetics ; Dirofilaria repens/anatomy & histology/genetics/*isolation & purification ; Dirofilariasis/*diagnosis/parasitology/*pathology ; Eye/*parasitology ; Eye Diseases/parasitology ; Female ; Humans ; Male ; Middle Aged ; Molecular Diagnostic Techniques/methods ; Parasitology/methods ; Phylogeny ; Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Homology ; Skin Diseases/parasitology ; Subcutaneous Tissue/*parasitology ; Vietnam

The aim of this study was to investigate the clinical, pathological and biological features of biphenotypic acute leukemia. The morphology of tumor cells was observed by bone marrow examination; the immunophenotype was assayed by flow cytometry and immunohistochemistry; the chromosomal aberrations were detected by conventional chromosomal analysis and RT-multiplex nested PCR. The results showed that extramedullary skin lesions and myelodysplasia occurred before the onset of overt disease. At the time of diagnosis, this case had more than 30% blasts in bone marrow with meningeal involvement. Large-sized tumor cells predominated morphologically over other cells. Flow cytometry revealed the co-expression of myeloid antigens (cMPO, CD33 and CD117) and T-lymphoid antigens (cCD3, CD5, CD7, dual expression of CD4 and CD8). Immunohistochemical staining showed that CD43 and CD99 were strong positive which define the earliest hematopoietic progenitors. Partial tandem duplication of the MLL gene could be detected with normal cytogenetic method. All above-mentioned results led to the diagnosis of biphenotypic acute leukemia. It is concluded that the biphenotypic acute leukemia is an uncommon type of leukemia which may be preceded by myelodysplastic syndrome and has aggressive clinical and biological behavior. Immunophenotype, cytogenetics and molecular analysis can contribute to early diagnosis of BAL and evaluation of prognosis.
12E7 Antigen ; Acute Disease ; Antigens, CD ; metabolism ; Cell Adhesion Molecules ; metabolism ; Child, Preschool ; Diagnosis, Differential ; Histone-Lysine N-Methyltransferase ; Humans ; Immunophenotyping ; Leukemia ; diagnosis ; genetics ; Leukosialin ; metabolism ; Male ; Myelodysplastic Syndromes ; complications ; Myeloid-Lymphoid Leukemia Protein ; genetics ; Skin Diseases ; complications ; Tandem Repeat Sequences

OBJECTIVEChronic granulomatous disease (CGD) is a rare primary immunodeficiency of phagocytic oxidative bursts leading to recurrent severe bacterial and fungal infections as well as granuloma formation. There were few reports on the clinical characteristics of this disease in China. The purpose of this study was to evaluate the clinical features of 48 Chinese cases with CGD which were confirmed by clinical features, dihydrorhodamine (DHR) assay and gene mutation analysis.

METHODThe study cohort was the population of CGD patients diagnosed in Children's Hospital of Fudan University from January, 2004, to June, 2011. Cases included in our analysis were restricted to those who had complete data of the clinical symptoms and laboratory tests. The patients were followed up by outpatient visiting and telephone call regularly for 0.5 to 6 years. The history and data of physical examination and treatment of 48 cases were collected and reviewed.

RESULTAll the patients were diagnosed by DHR analysis. The age of onset of all the 48 patients were less than 6 months, including 43 male and 5 female. The mean age at diagnosis was 2.42 years; 12 patients were infants under six months, 10 were between 6 and 12 months, 9 were between 1 and 2 years, 5 patients were between 2 and 3 years, 4 were between 4 and 5 years, and 8 were between 6 and 10 years. Recurrent respiratory infection (44/48) and chronic diarrhea (31/48) were the common symptoms in all the patients, and then skin lesion (22/48), including marked reaction at BCG infected site, pustular eruption and infected skin ulcer and urinary tract infection (3/48) were also general symptoms in our study. In addition, lymphadenectasis occurred in 31 cases and 23 of them were considered to be associated with BCG vaccination. The pathogens caused the infection were mycobacteria (52.08%), fungi (43.75%) and pyogenic bacteria. Thirty-seven patients had mutations in CYBB/CYBA/NCF1/NCF2 genes. Recombinant human interferon-gamma (rhIFN-γ) plus sulfamethoxazole were used for the prevention and treatment of infection, the frequency and severity of the disease could be reduced.

CONCLUSIONThe age at onset and diagnosis of the present group of CGD was younger. Clinical symptoms were associated with recurrent mycobacterial, fungal and pyogenic bacterial infection, which involved respiratory tract, alimentary tract, skin and lymph node. rhIFN-γ partially improved the prognosis of CGD.

Bacterial Infections ; epidemiology ; etiology ; prevention & control ; Child ; Child, Preschool ; Female ; Gastrointestinal Diseases ; epidemiology ; etiology ; prevention & control ; Granulomatous Disease, Chronic ; complications ; diagnosis ; genetics ; Humans ; Infant ; Interferon-gamma ; therapeutic use ; Lung Diseases ; epidemiology ; etiology ; prevention & control ; Male ; Mutation ; Mycobacterium Infections ; epidemiology ; etiology ; prevention & control ; Recombinant Proteins ; Retrospective Studies ; Skin Diseases ; epidemiology ; etiology ; prevention & control

The incidence of pulmonary embolism (PE) rises markedly with age, and only a few cases have been reported in younger adults. Thrombophilia has been reported as one of the predisposing factors for PE in younger adults. Here we report an extraordinary case of PE complicated with dysplasminogenemia, a rare genetic disorder resulting in hypercoagulability, in a young male. An 18-yr-old male visited an emergency room in the United States complaining chest discomfort. He was diagnosed as PE with deep vein thrombosis without apparent risk factors. Anticoagulation therapy with warfarin had been initiated and discontinued after 6 months of treatment. After returning to Korea he was tested for thrombophilia which revealed decreased activity of plasminogen and subsequent analysis of PLG gene showed heterozygous Ala620Thr mutation. He was diagnosed with PE complicated with dysplasminogenemia. Life-long anticoagulation therapy was initiated. He is currently under follow-up without clinical events for 2 yr.
Acute Disease ; Adolescent ; Anticoagulants/therapeutic use ; Conjunctivitis/complications/*diagnosis ; Heterozygote ; Humans ; Male ; Plasminogen/*deficiency/genetics ; Polymorphism, Single Nucleotide ; Pulmonary Embolism/*diagnosis/drug therapy/etiology ; Risk Factors ; Skin Diseases, Genetic/complications/*diagnosis ; Tomography, X-Ray Computed ; Venous Thrombosis/etiology ; Warfarin/therapeutic use