An intronic mutation is associated with prolactinoma in a young boy, decreased penetrance in his large family, and variable effects on MEN1 mRNA and protein

Prolactinomas are rare tumors in prepubertal children. A prolactinoma in a young child may be due to sequence variants in genes that are known to cause these tumors (MEN1, PRKAR1A, AIP). An 11-year-old boy with a macroprolactinoma was treated with cabergoline and the tumor receded. We studied the patient and his family for genetic causes of this tumor. No mutations were present in the coding sequence of PRKAR1A and AIP. A novel heterozygous substitution (IVS3-7 c>a) was identified in intron 3 of MEN1. We also found an additional PCR amplicon that incorporated the entire intron 3 of the gene (210bp) in the patient's cDNA. The same amplicon was present with lower intensity in some of the control individuals who were not mutation carriers. Intron 3 harbors an in-frame stop codon and its incorporation is predicted to result in a prematurely terminated protein. We conclude that a novel MEN1 variation was identified in a young boy with prolactinoma and six of his relatives who did not prese

Intravascular thrombosis as a possible cause of transient cortical brain lesions: CT and MRI

Cortical brain lesions were identified on MRI and CT in 14 patients with a variety of diseases. Each of these patients developed neurologic symptoms, the most prominent of which were seizures, depressed mental status, and blurred vision or cortical blindness. Both the imaging and the neurologic abnormalities resolved spontaneously within a period ranging from 5 to 30 days. Due to location and evolution of the lesions over time we hypothesize that they are secondary to small cortical venous thromboses.J Comput Assist Tomog

Treatment of autoimmune premature ovarian failure

There is no known immunosuppressive therapy for autoimmune premature ovarian failure that has been proven safe and effective by prospective randomized placebo-controlled study. Nevertheless, immunosuppression using corticosteroids has been used on an empirical basis for this condition. Here we present two cases of young women with premature ovarian failure who were treated with glucocorticoids in the hopes of restoring fertility. The first case illustrates the potential benefit of such therapy, and the second case illustrates a potential risk. The first patient with histologically proven autoimmune oophoritis was treated with alternate day glucocorticoid treatment. She had return of menstrual bleeding six times and ovulatory progesterone concentrations four times over a 16 week period. The second patient with presumed but unconfirmed autoimmune ovarian failure was referred to us after having been treated with a 9 month course of corticosteroids. During that treatment her menses did not resume. The corticosteroid treatment was complicated by iatrogenic Cushing syndrome and osteonecrosis of the knee. Identifying patients with autoimmune premature ovarian failure presents the opportunity to restore ovarian function by treating these patients with the proper immune modulation therapy. On the other hand, potent immune modulation therapy can have major complications. Corticosteroid therapy for autoimmune premature ovarian failure should be limited to use in placebo-controlled trials designed to evaluate the safety and efficacy of such treatment.Hum Repro

Diffusion MR imaging: clinical applications.

International audienceWater self-diffusion, a recently discovered source of contrast on MR images, has already shown promise for some clinical applications. Most studies have been of the brain, essentially for technical reasons. Diffusion is useful in distinguishing the different components of brain tumors (cystic regions, edema, necrosis) from the tumor core itself. Recent studies have shown that diffusion is anisotropic in brain white matter (i.e., dependent on the fiber tract's orientation in space), offering new insights into myelin disorders. Diffusion is also dramatically altered in the minutes following ischemic injury in the cat brain, which may have tremendous impact for the diagnosis and management of hyperacute stroke. With ultrafast acquisition schemes, diffusion imaging has also been used outside the CNS, for instance, in the eye and kidney. Future applications include diffusion-localized spectroscopy and temperature imaging. This article reviews recent progress in this field and suggests potential applications