Multiple cutaneous and uterine leiomyomas is an autosomal dominant condition t hat results in benign smooth muscle tumours of the skin and, in females, uterine fibroids. This syndrome overlaps with hereditary leiomyom...Multiple cutaneous and uterine leiomyomas is an autosomal dominant condition t hat results in benign smooth muscle tumours of the skin and, in females, uterine fibroids. This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer syndrome in which affected individuals may develop the rare type II papil lary renal cell cancer, in addition to skin leiomyomas. Recently, heterozygous m utations in the gene encoding fumarate hydratase have been found to underlie bot h conditions. Fumarate hydratase is an enzyme that catalyses the conversion of f umarate to malate in the Kreb’s cycle and may also function as a tumour suppres sor gene. We report a family with multiple leiomyomas, uterine fibroids and papi llary renal cell cancer. The proband is a 77-year-old Polish woman who develop ed multiple cutaneous leiomyomas on her right upper arm in her thirties and subs equently underwent a hysterectomy for uterine fibroids in her forties. She has f our offspring: her eldest daughter also has skin and uterine leiomyomas with a s imilar onset; her son has multiple skin leiomyomas and in addition was diagnosed with metastatic papillary renal cell cancer at the age of 50 years; the two you ngest daughters are unaffected. DNA sequencing in all the affected individuals d isclosed a heterozygous G ?úC substitution at nucleotide 173 ofthefumaratehydra tasegene,thatconvertsanarginineresidue (CGA) to proline (CCA). This missense mut ation has not been reported previously and is designated R58P. Interestingly, th e clinically asymptomatic 20-year-old son of the individual with renal cancer was also found to be heterozygous for R58P. It is likely that he will develop sk in leiomyomas in the future but the risk of renal cancer is difficult to predict . Nevertheless, detection of this mutation has important implications for screen ing and genetic counselling in this and other family members.展开更多
The acid perfusion test (APT) is a test of esophageal acid sensitivity. In gastroesophageal reflux disease (GERD), the APT has largely been superseded by indexes derived from 24- hr esophageal pH monitoring: symptom i...The acid perfusion test (APT) is a test of esophageal acid sensitivity. In gastroesophageal reflux disease (GERD), the APT has largely been superseded by indexes derived from 24- hr esophageal pH monitoring: symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP). To evaluate the role of APT in patients with GERD we compared values of SI, SSI, and SAP in 126 APT+ and 146 APT- patients. Median values for SI, SSI, and SAP were higher in the APT+ compared with the APT- group (P < 0.001). More patients had a positive SI, SSI, and SAP in the APT+ compared with the APT- group (SI, P < 0.0001; SSI and SAP, P < 0.001). Patients with a negative APT were unlikely to have symptoms caused by acid reflux (negative predictive value, 86% ). APT may be useful in detecting acid sensitivity in patients who do not report symptoms on 24- hr esophageal pH monitoring.展开更多
文摘Multiple cutaneous and uterine leiomyomas is an autosomal dominant condition t hat results in benign smooth muscle tumours of the skin and, in females, uterine fibroids. This syndrome overlaps with hereditary leiomyomatosis and renal cell cancer syndrome in which affected individuals may develop the rare type II papil lary renal cell cancer, in addition to skin leiomyomas. Recently, heterozygous m utations in the gene encoding fumarate hydratase have been found to underlie bot h conditions. Fumarate hydratase is an enzyme that catalyses the conversion of f umarate to malate in the Kreb’s cycle and may also function as a tumour suppres sor gene. We report a family with multiple leiomyomas, uterine fibroids and papi llary renal cell cancer. The proband is a 77-year-old Polish woman who develop ed multiple cutaneous leiomyomas on her right upper arm in her thirties and subs equently underwent a hysterectomy for uterine fibroids in her forties. She has f our offspring: her eldest daughter also has skin and uterine leiomyomas with a s imilar onset; her son has multiple skin leiomyomas and in addition was diagnosed with metastatic papillary renal cell cancer at the age of 50 years; the two you ngest daughters are unaffected. DNA sequencing in all the affected individuals d isclosed a heterozygous G ?úC substitution at nucleotide 173 ofthefumaratehydra tasegene,thatconvertsanarginineresidue (CGA) to proline (CCA). This missense mut ation has not been reported previously and is designated R58P. Interestingly, th e clinically asymptomatic 20-year-old son of the individual with renal cancer was also found to be heterozygous for R58P. It is likely that he will develop sk in leiomyomas in the future but the risk of renal cancer is difficult to predict . Nevertheless, detection of this mutation has important implications for screen ing and genetic counselling in this and other family members.
文摘The acid perfusion test (APT) is a test of esophageal acid sensitivity. In gastroesophageal reflux disease (GERD), the APT has largely been superseded by indexes derived from 24- hr esophageal pH monitoring: symptom index (SI), symptom sensitivity index (SSI), and symptom association probability (SAP). To evaluate the role of APT in patients with GERD we compared values of SI, SSI, and SAP in 126 APT+ and 146 APT- patients. Median values for SI, SSI, and SAP were higher in the APT+ compared with the APT- group (P < 0.001). More patients had a positive SI, SSI, and SAP in the APT+ compared with the APT- group (SI, P < 0.0001; SSI and SAP, P < 0.001). Patients with a negative APT were unlikely to have symptoms caused by acid reflux (negative predictive value, 86% ). APT may be useful in detecting acid sensitivity in patients who do not report symptoms on 24- hr esophageal pH monitoring.
