Bilateral leg ulcers secondary to dystrophic calcinosis in a patient with rheumatoid arthritis.

Calcinosis cutis can be classified into four subtypes: dystrophic, metastatic, idiopathic, and iatrogenic. Of these subtypes, dystrophic calcinosis (DC) is the most common, and is most frequently associated with connective tissue disease, particularly dermatomyositis and systemic sclerosis, and less commonly with systemic lupus erythematosus. However, DC associated with rheumatoid arthritis (RA) is extremely rare. In this paper, we present a Japanese woman with RA, who suffered from bilateral leg ulcers secondary to DC. To the best of our knowledge, only two cases of DC associated with RA have been reported to date. Similar to this case, the DC lesions were observed in the extremities, including the buttocks in the other two cases. Although the ulcers on her left leg were gradually epithelialized after one year, they may easily recur due to whitish abnormal underlying tissues, and a large ulcer remains on her right leg. Thus, it is important for physicians to identify DC when encountering non-healing leg ulcers associated with connective tissue diseases. J. Med. Invest. 64: 308-310, August, 2017.

Targeted exome sequencing and chromosomal microarray for the molecular diagnosis of nevoid basal cell carcinoma syndrome.

BACKGROUND: Nevoid basal cell carcinoma syndrome (NBCCS) is an autosomal dominant disorder mainly caused by heterozygous mutations of PTCH1. In addition to characteristic clinical features, detection of a mutation in causative genes is reliable for the diagnosis of NBCCS; however, no mutations have been identified in some patients using conventional methods. OBJECTIVE: To improve the method for the molecular diagnosis of NBCCS. METHODS: We performed targeted exome sequencing (TES) analysis using a multi-gene panel, including PTCH1, PTCH2, SUFU, and other sonic hedgehog signaling pathway-related genes, based on next-generation sequencing (NGS) technology in 8 cases in whom possible causative mutations were not detected by previously performed conventional analysis and 2 recent cases of NBCCS. Subsequent analysis of gross deletion within or around PTCH1 detected by TES was performed using chromosomal microarray (CMA). RESULTS: Through TES analysis, specific single nucleotide variants or small indels of PTCH1 causing inferred amino acid changes were identified in 2 novel cases and 2 undiagnosed cases, whereas gross deletions within or around PTCH1, which are validated by CMA, were found in 3 undiagnosed cases. However, no mutations were detected even by TES in 3 cases. Among 3 cases with gross deletions of PTCH1, deletions containing the entire PTCH1 and additional neighboring genes were detected in 2 cases, one of which exhibited atypical clinical features, such as severe mental retardation, likely associated with genes located within the 4.3Mb deleted region, especially. CONCLUSION: TES-based simultaneous evaluation of sequences and copy number status in all targeted coding exons by NGS is likely to be more useful for the molecular diagnosis of NBCCS than conventional methods. CMA is recommended as a subsequent analysis for validation and detailed mapping of deleted regions, which may explain the atypical clinical features of NBCCS cases.

Disruption of mouse XAB2 gene involved in pre-mRNA splicing, transcription and transcription-coupled DNA repair results in preimplantation lethality.

The XAB2 protein (XPA-binding protein 2) with 15 tetratricopeptide repeat motifs has been isolated by virtue of its ability to interact with xeroderma pigmentosum group A (XPA) protein in the yeast two-hybrid system. It has been shown that XAB2 interacted with Cockayne syndrome groups A and B (CSA and CSB) proteins and RNA polymerase II, which are known to be involved in transcription-coupled repair (TCR) and transcription, and that the antibodies against XAB2 protein inhibited the recovery of RNA synthesis after UV irradiation and normal RNA synthesis when microinjected into living fibroblasts. These results have indicated that XAB2 is involved in TCR and transcription. In this report, to elucidate the function of XAB2 in vivo, two types of mutations were introduced into the XAB2 gene in mice: a deletion of the region encompassing the promoter and exons 1-4, and a deletion of the C-terminal 162 amino acids. Both types of XAB2-heterozygous mice appeared normal physiologically and behaviorally. However, XAB2-homozygotes were selectively absent among the newborn mice. A detailed analysis of embryos at different stages of development indicated that the XAB2-homozygous mutants could survive until the morula stage, but could not develop to the blastocyst stage. These results indicate that XAB2 has an essential function in mouse embryogenesis.

Keratinocytes can differentiate into eccrine sweat ducts in vitro: involvement of epidermal growth factor and fetal bovine serum.

BACKGROUND: in addition to formation of an epidermal sheet and dermal substitution, reconstruction of skin that possesses functionality is an important goal for dermatologists. OBJECTIVE: we attempted to regenerate eccrine sweat glands in vitro. METHODS: we constructed skin equivalent models with various combination of normal human keratinocytes and fibroblasts and also examined the effect of various growth factors. RESULTS: we found that keratinocytes invaded the collagen gels and formed eccrine duct-like structures, only when (i) the culture media contained at least 15 ng/ml of epidermal growth factor (EGF) and fetal bovine serum (FBS), (ii) the keratinocytes were derived from young donors, and (iii) fibroblasts were present in the gel. Interestingly, when cultured under the same conditions eccrine gland duct cells were unable to invade the gel. Immunohistochemical analyses revealed induction of carcinoembryonic antigen by EGF at the inner part of the eccrine duct-like structures. Proliferating cell nuclear antigen was expressed mainly in basal layers of the epithelia but was not observed in the deeply invaded part. Cytokeratin profiles of the reconstructed epithelia were consistent with those of the regenerating epidermis and partly with the eccrine sweat duct. CONCLUSIONS: although not perfect model, these results indicate that 'young' keratinocytes could differentiate into/toward eccrine sweat ducts in vitro in the presence of EGF and FBS in cooperation with dermal fibroblasts.

Correction of a deformed thumb by distraction of the phalanx.

We used distraction osteogenesis to correct six deformed thumbs in four patients ranging in age from 4 to 7 years. Two of the patients had Apert syndrome (syndromic craniosynostosis with symmetrical syndactyly) and two had polydactyly. We used a small fixator with a ball joint and successfully corrected the angular deformity after lengthening the proximal phalanx by distraction. This single inclusive procedure was extremely useful. We found the optimal distraction regimen for the digital phalanx was a one day waiting period and lengthening at 1 mm/day. The mean healing indexes were 37.2 days/cm (range 24.2 to 41.5) in those with Apert syndrome and 64.3 days/cm in those with polydactyly (62.5 and 66.0). Our results suggest that osteogenesis at the distraction site may be quicker in patients with Apert syndrome than in those with polydactyly.

Case of erythema nodosum associated with granulomatous mastitis probably due to Corynebacterium infection.

Granulomatous mastitis (GM) is a rare chronic inflammatory breast disease that can be mistaken for a variety of inflammatory and neoplastic disorders of the breast. Erythema nodosum (EN) is a common panniculitis, and is often associated with a variety of diseases, yet coexistence of EN and GM is very rare. In this paper, we present a young Japanese woman with EN associated with GM probably due to Corynebacterium infection. Both lesions of EN and GM were successfully treated with oral minocycline and surgical drainage. To the best of our knowledge, this is the first case of EN associated with GM due to Corynebacterium infection in the English-language published work.