5 research outputs found
Soft tissue angiofibroma: Clinicopathologic, immunohistochemical and molecular analysis of 14 cases
Soft tissue angiofibroma is rare and has characteristic histomorphological and genetic features. For diagnostic purposes, there are no specific antibodies available. Fourteen lesions (6 females, 8 males; age range 7â67 years) of the lower extremities (12) and trunk (2) were investigated by immunohistochemistry, including for the first time NCOA2. NCOA2 was also tested in a control group of other spindle cell lesions. The known fusionâgenes (AHRRâNCOA2 and GTF2IâNCOA2) were examined using RTâPCR in order to evaluate their diagnostic value. Cases in which no fusion gene was detected were additionally analysed by RNA sequencing. All cases tested showed nuclear expression of NCOA2. However, this was not specific since other spindle cell neoplasms also expressed this marker in a high percentage of cases. Other variably positive markers were EMA, SMA, desmin and CD34. STAT6 was negative in the cases tested. By RTâPCR for the most frequently observed fusions, an AHRRâNCOA2 fusion transcript was found in 9/14 cases. GTF2IâNCOA2 was not detected in the remaining cases (nâ=â3). RNA sequencing revealed three additional positive cases; two harbored a AHRRâNCOA2 fusion and one case a novel GAB1âABL1 fusion. Two cases failed molecular analysis due to poor RNA quality. In conclusion, the AHRRâNCOA2 fusion is a frequent finding in soft tissue angiofibroma, while GTF2IâNCOA2 seems to be a rare genetic event. For the first time, we report a GAB1âABL1 fusion in a soft tissue angiofibroma of a child. Nuclear expression of NCOA2 is not discriminating when compared with other spindle cell neoplasms
PATIENTS WITH AUTOSOMAL NEPHROGENIC DIABETES-INSIPIDUS HOMOZYGOUS FOR MUTATIONS IN THE AQUAPORIN-2 WATER-CHANNEL GENE
Mutations in the X-chromosomal V2 receptor gene are known to cause nephrogenic diabetes insipidus (NDI). Besides the X-linked form, an autosomal mode of inheritance has been described. Recently, mutations in the autosomal gene coding for water-channel aquaporin 2 (AQP2) of the renal collecting duct were reported in an NDI patient. In the present study, missense mutations and a single nucleotide deletion in the aquaporin 2 gene of three NDI patients from consanguineous matings are described. Expression studies in Xenopus oocytes showed that the missense AQP2 proteins are nonfunctional. These results prove that mutations in the AQP2 gene cause autosomal recessive NDI