Cryptococcosis has been reported to be mostly associated with non-HIV-related patients in China. However, little is known about the molecular charact

Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease that is primarily characterized by multiple café au-lait spots (CALs) and skin neurofibromas, which are attributed to defects in the tumor suppressor NF1. Because of the age-dependent presentation of NF1, it is often difficult to make an early clinical diagnosis. Moreover, identifying genetic alterations in NF1 patients represents a complex challenge. Currently, there are no effective detective methods and no comprehensive NF1 mutation data are available for mainland China. We screened 109 Chinese patients from 100 families with NF1-like phenotypes (e.g., CALs, neurofibromas, etc.) using Sanger sequencing, multiplex ligation-dependent probe amplification and cDNA sequencing. NF1 mutations were identified in 97 individuals, among which 34 intragenic mutations have not previously been reported. Our exhaustive mutational analysis detected mutations in 89% (89/100) of the NF1-like probands and 93% (70/75) of subjects fulfilling the National Institutes of Health (NIH) criteria. Our findings indicate that individuals who exclusively present with multiple CALs exhibit a high possibility (76%) of having NF1 and show a significantly lower mutation rate (p = 0.042) compared with subjects who fulfill the NIH criteria, providing clinicians with the information that subjects only with multiple CALs harbor a considerable possibility (24%) of being attributed to other comparable diseases.

Cryptococcosis is the third most common deep fungal infection in China and has not yet been reported to be associated with HIV infection there. We report the management of non-HIV-related cryptococcosis, including cutaneous cryptococcosis, pulmonary cryptococcosis and cryptococcal infection of central nervous system (CNS). Establishment of the diagnosis of cutaneous cryptococcosis and pulmonary cryptococcosis were mainly based on the histopathologic examination and mycologic culture, with CNS cryptococcal infection based on mycologic examination and latex agglutination test on cerebrospinal fluid. The treatment of cutaneous cryptococcosis included systemic administration of amphotericin B (AMB), 5-flucytosine and triazole agents such as fluconazole and itraconazole combined with topical ketoconazole cream. Treatment of pulmonary cryptococcosis included systemic use of antifungal medication combined with surgical removal of pulmonary lesions. The treatment of CNS cryptococcal infection was challenging. In this study, 53 patients with CNS cryptococcal infection were divided into three groups according to the antifungal regimens applied: eight patients (group I) received intravenous AMB alone or in combination with 5-flucytosine, five patients (group II) received intravenous fluconazole alone or with 5-flucytosine, and 40 patients (group III) received a two-phase therapy, active therapy and consolidation therapy. In active therapy, the patients received intrathecal and intravenous administration of AMB alone or with 5-flucytosine until the mycological culture of cerebrospinal fluid (CSF) became negative. Consolidation therapy followed active therapy by continuous use of oral fluconazole or itraconazole until direct microscopic examination of CSF was negative for three consecutive weeks. In group I, five patients were cured, two improved, one died and one had relapse. In group II, two patients were cured, one improved and two died. In group III, thirty-nine out of forty patients were cured without recurrence. These results indicate that the two-phase protocol was more desirable for the treatment of non-HIV associated cryptococcal infection of CNS.