BACKGROUND: Monocyte-macrophage lineage cells are committed towards osteoclast differentiation in vitro by the downregulation of microphthalmia-induced transcription factor (MITF) by miRNA-155. Therefore, we aimed to evaluate miRNA-155 expression and explore the regulation of MITF by miRNA-155 during osteoclastogenesis in periodontitis.
METHODS: Ninety-eight subjects were recruited and categorized into the following: group I (cases)-systemically healthy with localized stage III/IV periodontitis (N = 49) and group II (controls)-systemically and periodontally healthy (N = 49). Gingival tissue samples were procured and qRT-PCR analysis was carried out for relative gene expression.
RESULTS: The mean ΔCT of miRNA-155 expression was -1.04 ± 2.26 and -0.01 ± 1.4 respectively for groups I and II. There was a statistically significant difference in the miRNA-155 expression (P ≤ 0.01) between the groups. The mean ΔCT of MITF expression for groups I and II was 4.15± 2.16 and 3.51± 1.57 respectively with no significant difference (P > 0.01) between the groups. In the periodontitis group, miRNA-155 expression increased by fivefolds (P ≤ 0.01) whereas MITF expression showed no significant difference in the fold change between the groups (P > 0.01). The site-specific clinical parameters showed a statistically significant strong negative and positive correlation with the ΔCT and fold change values of miRNA-155 respectively in the total 98 samples (P < 0.01). miRNA-155 was able to discriminate between periodontal health and disease with a diagnostic accuracy of 96.9% (95%CI: 91.38-98.95) and the AUC was 0.98 (95%CI: 0.97-1.0, SE = 0.008, P < 0.001) in ROC analysis with a sensitivity of 93.8% (95%CI: 83.48-97.9) and specificity of 100% (95%CI: 92.73-100).
CONCLUSIONS: miRNA-155 was dysregulated and upregulated by fivefolds in periodontal disease. It can be used as a potential biomarker to discriminate between periodontal health and disease. No difference in the MITF gene expression was demonstrated between periodontal health and disease. The result suggested that miRNA-155 does not affect the expression of MITF gene in the process of osteoclastogenesis in localized stage III/IV periodontitis within this study design and limitations.

暂无摘要。

BACKGROUND: The microphthalmia-associated transcription factor gene (MITF) belongs to the MYC supergene family and plays an important role in melanocytes\' homeostasis. Individuals harboring MITF germline pathogenic variants are at increased risk of developing cancer, most notably melanoma and renal cell carcinoma.
METHODS: We describe a cohort of ten individuals who harbor the same MITF c.952G > A (p.Glu 318Lys), or p.E318K, germline pathogenic variant. Six carriers developed at least one malignancy (4 cases of breast cancer; 1 cervical cancer; 1 colon cancer; 1 melanoma; 1 ovarian/fallopian tube cancer). A significant phenotypic heterogeneity was found among these individuals and their relatives. Breast cancer was, overall, the most frequent malignancy observed in this case series, with 13 occurrences of 60 (21.67 %) total cancer cases described among the probands and their relatives.
CONCLUSIONS: Our retrospective analysis data raise the hypothesis of a possible association of the MITF p.E318K pathogenic variant with an increased risk of breast cancer.

Waardenburg syndrome (WS) is a rare genetic disorder. The purpose of this study was to investigate clinical and molecular characteristics of WS in four probands from four different Iranian families.
The first patient was a 1-year-old symptomatic boy with congenital hearing loss and heterochromia iridis with a blue segment in his left iris. The second case was a 1.5-year-old symptomatic girl who manifested congenital profound hearing loss, brilliant blue eyes, and skin hypopigmentation on the abdominal region at birth time. The third patient was an 8-month-old symptomatic boy with developmental delay, mild atrophy, hypotonia, brilliant blue eyes, skin hypopigmentation on her hand and foot, Hirschsprung disease, and congenital profound hearing loss; the fourth patient was a 4-year-old symptomatic boy who showed dystopia canthorum, broad nasal root, synophrys, skin hypopigmentation on her hand and abdomen, brilliant blue eyes, and congenital profound hearing loss. Whole exome sequencing (WES) was used for each proband to identify the underlying genetic factor. Sanger sequencing was performed for validation of the identified mutations in probands and the available family members. A novel heterozygous frameshift mutation, c.996delT (p.K334Sfs*15), on exon 8 of the MITF gene was identified in the patient of the first family diagnosed with WS2A. Two novel de novo heterozygous mutations including a missense mutation, c.950G > A (p.R317K), on exon 8 of the MITF gene, and a frameshift mutation, c.684delC (p.E229Sfs*57), on the exon 3 of the SOX10 gene were detected in patients of the second and third families with WS2A and PCWH (Peripheral demyelinating neuropathy, Central dysmyelinating leukodystrophy, Waardenburg syndrome, Hirschsprung disease), respectively. A previously reported heterozygous frameshift mutation, c.1024_1040del AGCACGATTCCTTCCAA, (p.S342Pfs*62), on exon 7 of the PAX3 gene was identified in the patient of the fourth family with WS1.
An exact description of the mutations responsible for WS provides useful information to explain the molecular cause of clinical features of WS and contributes to better genetic counseling of WS patients and their families.

Hearing loss (HL) represents the most common congenital sensory impairment with an incidence of 1-5 per 1000 live births. Non-syndromic hearing loss (NSHL) is an isolated finding that is not part of any other disorder accounting for 70% of all genetic hearing loss cases.
In the current study, we reported a polygenic mode of inheritance in an NSHL consanguineous family using exome sequencing technology and we evaluated the possible effect of the detected single nucleotide variants (SNVs) using in silico methods.
Two bi-allelic SNVs were detected in the affected patients; a MYO15A (. p.V485A) variant, and a novel MITF (p.P338L) variant. Along with these homozygous mutations, we detected two heterozygous variants in well described hearing loss genes (MYO7A and MYH14). The novel MITF p. Pro338Leu missense mutation was predicted to change the protein structure and function.
A novel MITF mutation along with a previously described MYO15A mutation segregate with an autosomal recessive non-syndromic HL case with a post-lingual onset. The findings highlight the importance of carrying whole exome sequencing for a comprehensive assessment of HL genetic heterogeneity.

Waardenburg syndrome (WS) is an orphan genetic disease with autosomal dominant pattern of inheritance characterised by varying degrees of hearing loss accompanied by skin, hair and iris pigmentation abnormalities. Four types of WS differing in phenotypic characteristics are now described. We performed a Sanger sequencing of coding regions of genes PAX3, MITF, SOX10 and SNAI2 in the patient with WS from a Yakut family living in the Sakha Republic. No changes were found in the PAX3, SOX10 and SNAI2 coding regions while a previously reported heterozygous transition c.772C>T (p.Arg259*) in exon 8 of the MITF gene was found in this patient. This patient presents rare phenotype of WS type 2: congenital unilateral hearing loss, unilateral heterochromia of irises, and absence of skin/hair depigmentation and dystopia canthorum. Audiological variability in WS type 2, caused by the c.772C>T (p.Arg259*) variant in the MITF gene, outlines the importance of molecular analysis and careful genotype-phenotype comparisons in order to optimally inform patients about the risk of hearing loss. The results of this study confirm the association of pathogenic variants in the MITF gene with WS type 2 and expanded data on the variability of audiological features of the WS.

Clear cell sarcoma of soft tissues is a very rare, malignant soft tissue tumor that usually arises in the extremities, with a predilection for the lower limbs. This report presents a 45-year-old male with a painless mass in the right lumbar region for one year. Magnetic resonance imaging showed a 3.6×3.2×1.5-cm soft tissue mass of the right lumbar region. The tumoral cells had pleomorphic nuclei and large amounts of clear cytoplasm, and a proportion of the cells contained melanin. Immunohistochemical analysis was performed, which identified that the cells were positive for S-100, MITF and HMB-45 tumor markers. The patient underwent a postoperative chemotherapy protocol and had no local recurrences at one year post-surgery.

Microphthalmia-associated Transcription Factor, MITF, is a master regulator of melanocyte development, differentiation, migration, and survival.(1) A broad collection of studies have indicated that MITF directly regulates the transcription of genes involved in pigmentation, which are selective to the melanocyte lineage. In addition, MITF controls expression of genes which are expressed in multiple cell lineages, and may also play differential roles in activating vs. maintaining gene expression patterns. In this Point of View article, we discuss lineage restricted transcription factor activation of both tissue-specific and ubiquitously expressed genes using melanocytes and MITF as a model system that may eventually provide insights into such processes in multiple cell lineages.