Neurofibromatosis type 1 protein and amyloid precursor protein interact in normal human melanocytes and colocalize with melanosomes.
(9/48)
The neurofibromatosis type 1 (NF1) gene product, neurofibromin, is known to interact with Ras, thereby negatively regulating its growth-promoting function. Although this is a well-established interaction, the discovery of other neurofibromin interacting partners could reveal new functional properties of this large protein. Using yeast two-hybrid analysis against a brain cDNA library, we identified a novel interaction between the amyloid precursor protein and the GTPase activating protein-related domain of neurofibromin. This interaction was further analyzed in human melanocytes and confirmed by immunoprecipitation and colocalization studies. In addition, we observed a colocalization of amyloid precursor protein and neurofibromin with melanosomes. Amyloid precursor protein has been proposed to function as a vesicle cargo receptor for the motor protein kinesin-1 in neurons. This colocalization of amyloid precursor protein and neurofibromin with melanosomes was lost in melanocytes obtained from normal skin of a NF1 patient. We suggest that a complex between amyloid precursor protein, neurofibromin, and melanosomes might be important in melanosome transport, which could shed a new light on the etiopathogenesis of pigment-cell-related manifestations in NF1. (+info)
Segmental neurofibromatosis of face.
(10/48)
A 38-year-old man presented with asymptomatic skin lesions over the left side of the face of 5-years duration. He had multiple discrete soft-to-firm papules and nodules on the left side of the face along the distribution of the mandibular division of the trigeminal nerve. Histopathology examination of one of the nodules (face) showed a non-encapsulated tumor of the dermis with normal overlying epidermis. The tumor consisted of loosely spaced spindle cells and wavy collagenous strands in a clear matrix. These features were consistent with our clinical diagnosis of segmental neurofibromatosis. This case is reported for its rarity and typical manifestations. (+info)
Cafe-au-lait patches and senile plaques: How APPt the connection?
(11/48)
Neurofibromatosis type 1 (NF1) is a genetic disease caused by mutations in the NF1 gene, which encodes the protein neurofibromin. Patients exhibit characteristic hyperpigmented patches called cafe-au-lait patches. Melanocytes of NF1 patients differ from normal human melanocytes, but no differences account completely for lesional hyperpigmentation. An association between beta-amyloid precursor protein (APP) and neurofibromin, and their localization to the melanosome, may help explain the development of cafe-au-lait patches. (+info)
PMS2 mutations in childhood cancer.
(12/48)
Until recently, the PMS2 DNA mismatch repair gene has only rarely been implicated as a cancer susceptibility locus. New studies have shown, however, that earlier analyses of this gene have had technical limitations and also that the genetic behavior of mutant PMS2 alleles is unusual, in that, unlike MLH1 or MSH2 mutations, PMS2 mutations show low heterozygote penetrance. As a result, a dominantly inherited cancer predisposition has not been a feature reported in families with PMS2 mutations. Such families have instead been ascertained through childhood-onset cancers in homozygotes or through apparently sporadic colorectal cancer in heterozygotes. We present further information on the phenotype associated with homozygous PMS2 deficiency in 13 patients from six families of Pakistani origin living in the United Kingdom. This syndrome is characterized by cafe-au-lait skin pigmentation and a characteristic tumor spectrum, including leukemias, lymphomas, cerebral malignancies (such as supratentorial primitive neuroectodermal tumors, astrocytomas, and glioblastomas), and colorectal neoplasia with an onset in early adult life. We present evidence for a founder effect in five families, all of which carried the same R802-->X mutation (i.e., arginine-802 to stop) in PMS2. This cancer syndrome can be mistaken for neurofibromatosis type 1, with important management implications including the risk of the disorder occurring in siblings and the likelihood of tumor development in affected individuals. (+info)
Vitamin D deficiency associated with number of neurofibromas in neurofibromatosis 1.
(13/48)
Neurofibromatosis 1 (NF1) is a tumour suppressor gene syndrome characterized by multiple cutaneous and plexiform neurofibromas. Focal osseous abnormalities, short stature, and decreased bone mineral density are also frequent in people with NF1. We measured serum 25-hydroxyvitamin D concentrations in 55 patients with NF1 and 58 healthy controls, and correlated the findings in the patients with NF1 with their estimated number of dermal neurofibromas. Geometric mean (SD) serum 25-hydroxyvitamin D concentration was 14.0 (1.6) ng/mL among the patients with NF1 compared with 31.4 (1.7) ng/mL among healthy controls (p<<0.0001). The serum vitamin D concentration and number of dermal neurofibromas reported by patients with NF1 were inversely correlated (Spearman's rho = -0.572, p<0.00001). The occurrence of low serum vitamin D concentrations in people with NF1, especially those with many dermal neurofibromas, may provide new pathogenic insights and have important therapeutic implications. (+info)
Plexiform neurofibroma of the tongue: a case report of a child.
(14/48)
A three-year-old girl with a lingual plexiform neurofibroma treated by total excision is presented. Despite their occurrence in the head and neck region, neural sheath tumors are rarely encountered in the oral cavity. It is reported that 4-7% of patients affected by neurofibromatosis display oral manifestations. Neurofibromatosis is characterized by cafe-au-lait spots and cutaneous neurofibromas. Plexiform neurofibroma is said to be indicative of von Recklinghausen's disease (VRD) even though it may be the only manifestation of the disease. Generally, surgical resection represents the treatment of choice and the diagnosis can only be confirmed after histological examination. Affected patients need regular follow-up to detect malignant degeneration, an early recurrence or appearance of other manifestations of VRD. (+info)
A case of McCune-Albright syndrome with associated multiple endocrinopathies.
(15/48)
McCune-Albright syndrome (MAS) is a rare disorder that develops from an activating mutation in the Gs gene. It is characterized by an association with Polyostotic fibrous dysplasia, and precocious puberty, Caf-au-lait pigmentation, and other endocrinopathies that result from the hyperactivity of a variety of endocrine glands. Recently we encountered a patient with MAS with fibrous dysplasia, skin pigmentation, acromegaly, hyperprolactinemia and a thyroid nodule. A 23-year-old male presented for an evaluation of a change in his facial structures. Fibrous dysplasia was diagnosed by a bone biopsy and radiographic studies. The GH level increased paradoxically after an oral glucose load. The plasma prolactin, IGF-1 and alkaline phosphatase were high. Thyroid ultrasonography revealed multiple nodules. The brain MRI demonstrated a mass in the left pituitary gland. Genetic analysis identified a change from Arg (CGT) at codon 201 to Cys (TGT). (+info)
Facial plexiform neurofibroma in a child with neurofibromatosis type I: a case report.
(16/48)
Plexiform neurofibroma is a non-circumscribed, thick and irregular benign tumor of the peripheral nerve sheath. It is a virtually pathognomonic and often disabling feature of neurofibromatosis type I. The diffuse and soft nature of plexiform neurofibroma is often compared to 'a bag of worms' and is difficult to distinguish from a vascular malformation or a lymphangioma, thus necessitating thorough clinical and histopathological examination and imaging of the lesion. We present a case of plexiform neurofibroma in a 12-year-old male child. (+info)