Partial trisomy 1(q42-->qter): a new case with a mild phenotype.

We report a female patient with a 46,XX,der(8)t(1;8)(q42.1;p23.3) karyotype who had a mild phenotype characterised by a few subtle dysmorphic features and mild developmental retardation, probably resulting from trisomy 1q42-->qter. The deletion on the short arm of the chromosome 8 appeared to be confined to the distal chromosomal segment.     

Renal cancer steroid receptors: biochemical basis for endocrine therapy.

Estradiol receptor (ER) and progesterone receptor (PR), found in experimental renal cancer as well as in normal human kidney and in human renal cell carcinoma (RCC), have been measured in 27 RCCs from patients submitted to surgery and endocrine therapy in an attempt to predict the response to progestational therapy. Of these 27 tumors 59% were positive for ER and 59% for PR; 37% were positive and 19% negative for both ER and PR. The follow-up of 23 patients showed that progestational therapy, started in 18 patients, has given favorable results in 14 patients and negative results in 3 patients with ER-PR- renal cancer. Antiestrogenic therapy, started soon after nephrectomy in 1 patient with ER+PR- renal cancer and lung metastases, failed since the patient died 8 months after surgery.     

Occurrence of thanatophoric dysplasia type I (R248C) and hypochondroplasia (N540K) mutations in two patients with achondroplasia phenotype.

We report two patients with clinical and radiological findings of achondroplasia, who had the most common FGFR3 mutation occurring in thanatophoric dysplasia type I and hypochondroplasia, respectively. Thanatophoric dysplasia is usually a lethal condition, but the patient carrying this mutation is alive and presents a medical history similar to that of patients with achondroplasia. The events leading to such a discrepancy between genotype and phenotype are unclear. These rare cases may influence an appropriate medical and genetic counseling.     

Successful management of neonatal renal venous thrombosis

Renal vein thrombosis is the most common vascular condition involving the newborn kidney and it can result in severe renal damage. We report a newborn with renal vein thrombosis treated with continuous infusion of unfractionated heparin who had normal total renal function after 3 years of follow up, despite reduction of the functional contribution of the affected kidney.     

Nuclear steroid receptors and dysplasia in adenomatous polyps of the colon as markers of high risk for malignant transformation

To detect an early colon carcinoma in its stage of carcinoma in situ, colonoscopic examinations with removal of all adenomas of the left colon (particularly of the sigmoid tract and rectum), followed by histological and biochemical evaluations, have been performed on 30 patients. Two-thirds of the adenomas examined presented histological patterns of tubular, tubulovillous, and villous adenomas; those with moderate or severe dysplasia were at high risk of neoplastic transformation. Measurement of estradiol (ER) and progesterone (PR) receptors was performed in the cytosol and in the nuclei of solitary and multiple adenomas and in those with synchronous carcinomas using the dextran-coated-charcoal (DCC) method. Steroid receptors were usually found in the cytosol of the large polyps of male rather than female patients (46% vs 11%) and in the cytosol of the adenomas with moderate or severe dysplasia in male patients. Malignant lesions usually possessed both ER and PR in the cytosol and nuclear fraction. These findings led to hypothesize that patients with adenomas of the colorectal tract with moderate or severe dysplasia and nuclear steroid receptors should be considered at high risk for colon carcinoma and therefore need a special follow-up program.     

Steroid receptors in the pathogenesis of chronic subdural hematoma

Chronic subdural hematoma (CSDH), located between the dura mater and the arachnoid and usually characterized by a well-vascularized external capsule (HEM), has a higher incidence in male patients with elevated urinary estrogens than in female patients. In an attempt to increase our understanding of the physiopathogenesis of CSDH, total estrogen receptor (ER) was measured in HEM specimens from four male patients by a sodium thiocyanate exchange assay and cytosol progesterone receptor (PRc) in three specimens by a dextran-coated charcoal adsorption assay. Although no nuclear ER could be detected, ERc and PRc were found in all three specimens examined. The presence of ER in a mesenchymal tissue like HEM could suggest that, in addition to inducing vascular changes, estrogens might act directly on HEM through a receptor-mediated mechanism more pronounced in men than in women, whose vascular network is adapted to high estrogen values.     

Genetic analysis of the dystroglycan gene in bronchopulmonary dysplasia affected premature newborns

BACKGROUND: Dystroglycan (DG) is an extracellular matrix receptor that serves as an adhesion molecule and is essential for the stability of the plasma membrane. DG is highly expressed within the epithelial cell layer where it supports morphogenesis, adhesion and wound repair. Mechanically ventilated newborns often develop bronchopulmonary dysplasia (BPD), characterized by a progressive impairment of wound repair capacity in their lung. METHODS: To verify if the susceptibility to BPD might be linked to genetic abnormalities in the DG gene (DAG1), we searched for possible mutations in 33 premature newborns with gestational age<34 weeks with risk of developing BPD. DAG1 genotype was determined in 11 premature newborns with BPD as compared to 22 premature infants without lung complications. RESULTS: Eight polymorphisms were found, four of them being new DAG1 single nucleotide polymorphisms (SNPs). Only one significant association was found with BPD positive infants: the N494H homozygous genotype (p=0.033). The same polymorphism was found significantly associated with BPD when allelic frequencies were considered (p=0.0015). CONCLUSIONS: Our data enrich the list of DAG1 SNPs and could be useful to trigger further genetic studies about the involvement of DG in human diseases.     

Identification and characterisation of an 8.7 kb deletion and a novel nonsense mutation in two Italian families with Sanfilippo syndrome type D (mucopolysaccharidosis IIID)

Sanfilippo syndrome type D is an autosomal recessive lysosomal storage disease that is caused by a deficiency of N-acetylglucosamine-6-sulphatase, one of the enzymes involved in the catabolism of heparan sulphate. Only 15 patients have been described in the literature and just two mutations have been reported to date. We present the clinical, biochemical and molecular analysis of two Italian Sanfilippo D families. Novel homozygous mutations were identified in the affected patients from each family: a large intragenic deletion of 8723 bp encompassing exons 2 and 3 in family 1 and a nonsense mutation, Q272X, in family 2. The deletion is the first large intragenic deletion to be reported in any of the four Sanfilippo subtypes, including Sanfilippo type C in which the gene has recently been identified.