1.
Enigmatic in vivo GlcNAc-1-phosphotransferase (GNPTG) transcript correction to wild type in two mucolipidosis III gamma siblings homozygous for nonsense mutations.
Velho, RV, Ludwig, NF, Alegra, T, Sperb-Ludwig, F, Guarany, NR, Matte, U, Schwartz, IV
Journal of human genetics. 2016;(6):555-60
Abstract
Mucolipidosis (ML) III gamma is a rare autosomal-recessive disorder caused by pathogenic mutations in the GNPTG gene. GNPTG encodes the γ-subunit of GlcNAc-1-phosphotransferase that catalyzes mannose 6-phosphate targeting signal synthesis on soluble lysosomal enzymes. ML III gamma patients are characterized by missorting of lysosomal enzymes. In this report, we describe the probable occurrence of mRNA editing in two ML III gamma patients. Patients A and B (siblings) presented at the adult age with a typical clinical picture of ML III gamma, mainly compromising bone and joints, and high levels of lysosomal enzymes in plasma and low levels in fibroblasts. Both were found to be homozygous for c.-112C>G and c.328G>T (p.Glu110Ter) mutations in genomic DNA (gDNA) analysis of GNPTG. Analysis of complementary DNA (cDNA), however, showed normal genotypes for both patients. Low GNPTG mRNA expression was observed in both patients. The mRNA editing can explain the differences found in patients A and B regarding gDNA and cDNA analysis, and the mild clinical phenotype associated with homozygosity for a nonsense mutation. Our results suggest that mRNA editing can be more frequent than expected in monogenic disorders and that GNPTG analysis should be performed on gDNA.
2.
A case of cervical cancer expressed three mRNA variant of Hyaluronan-mediated motility receptor.
Villegas-Ruíz, V, Salcedo, M, Zentella-Dehesa, A, de Oca, EV, Román-Basaure, E, Mantilla-Morales, A, Dávila-Borja, VM, Juárez-Méndez, S
International journal of clinical and experimental pathology. 2014;(5):2256-64
Abstract
Cervical cancer is the second malignancy in Mexico, little is known about the prognostic factors associated with this disease. Several cellular components are important in their transformation and progression. Alternative mRNA splice is an important mechanism for generating protein diversity, nevertheless, in cancer unknown mRNA diversity is expressed. Hyaluronan-mediated motility receptor (HMMR, RHAMM, CD168) is a family member of proteins, hyaluronan acid dependent, and has been associated with different malignant processes such as: angiogenesis, cell invasiveness, proliferation, metastasis and poor outcome in some tumors. In the present study we identified expression of HMMR in cervical cancer by means of RT-PCR and sequencing. Our results indicate co-expression of two HMMR variants in all samples, and one case expressed three alternative HMMR splice transcripts. These results showed the heterogeneity of mRNA transcripts of HMMR that could express in cancer and the expression of HMMR could be marker of malignancy in CC.
3.
Open trial of topical tacalcitol [1 alpha 24(OH)2D3] and solar irradiation for vitiligo vulgaris: upregulation of c-Kit mRNA by cultured melanocytes.
Katayama, I, Ashida, M, Maeda, A, Eishi, K, Murota, H, Bae, SJ
European journal of dermatology : EJD. 2003;(4):372-6
Abstract
Vitiligo vulgaris is a common skin disease, however some cases show poor clinical responses to topical steroid ointment or PUVA therapy. Such regimens are generally avoided in the treatment of facial lesions or in pediatric cases because of the undesirable side effects. To confirm the excellent response to combination therapy with topical vitamin D3 ointment and solar irradiation for vitiligo achieved in the initial patients, we conducted an open trial on other patients, most of whom had poor clinical responses to the prior therapies. Fifteen patients (9 men and 6 women) with vitiligo vulgaris were enrolled in this study. Each patient was instructed to sunbathe for 30 minutes within 1 hour after topical application of the tacalcitol [1 alpha 24(OH)(2)D(3)] ointment or cream to the skin lesions every day. Six of 15 patients showed a fair and excellent clinical response to the combination therapy (more than 30% clearance of the vitiligo). The clinical effect was more apparent in patients with a history of less than 5 years of vitiligo (4 of 6 cases) in contrast to those with a history of more than 5 years (2 of 9 cases). In vitro experiments revealed that tacalcitol upregulated the expression of c-Kit mRNA by melanocytes irradiated with linear polarized infrared, UVA or short period solar irradiation. These results suggest that combination therapy with topical vitamin D(3) ointment and solar irradiation can be used as an alternate therapy for vitiligo vulgaris.