Crigler‐Najjar syndrome in The Netherlands: Identification of four novel UGT1A1 alleles,genotype–phenotype correlation,and functional analysis of 10 missense mutants

Crigler‐Najjar syndrome (CN), caused by deficiency of UGT isoform 1A1 (UGT1A1), is characterized by severe unconjugated hyperbilirubinemia. In this study we have analyzed 19 CN patients diagnosed in The Netherlands (18) and in Belgium (1), and have identified 14 different UGT1A1 mutations, four of which are novel. Two mutations were present in several unrelated patients, suggesting the presence of two founder effects in The Netherlands. In addition, we show linkage of the UGT1A1??28 promoter polymorphism (rs5719145insTA) to three structural mutations. Functional studies of partial active UGT1A1 mutants are limited. Therefore, we performed in vitro studies to determine the functional activity of seven missense mutants identified in this study and of three reported previously. In addition to bilirubin, we also determined their activity toward eight other UGT1A1 substrates. We demonstrate that five mutants have residual activity that, depending on the substrate, varies from not detectable to 94% of wild‐type UGT1A1 activity. The identification of four novel pathogenic mutations and the analysis of residual activity of 10 UGT1A1 missense mutants are useful for clinical diagnosis, and provides new insights in enzyme activity, whereas the identification of two founder mutations will speed up genetic counseling for newly identified CN patients in The Netherlands. Hum Mutat 30:1–8, 2009. © 2009 Wiley‐Liss, Inc.     

Screening for lymph nodes in the neck with ultrasound

In a study of the value of ultrasound in staging patients with head and neck malignancies, we performed ultrasound of the neck. The results of this investigation were compared with palpation. A fine needle aspiration biopsy and/or histologic examination was carried out on lymph nodes which were found. One hundred and six patients were included in this study. In 44 of the patients no lymph nodes could be detected, either on palpation or by ultrasound examination. In the other 62 patients all palpable lymph nodes were also demonstrated by ultrasound. However, in 20 patients with negative palpatory findings, ultrasound revealed lymph nodes: 11 metastases and 9 benign nodes. In 40 patients an ultrasound guided fine needle aspiration biopsy (UGFNAB) was performed. In 85% of these patients a cytological diagnosis could be made. From these results we conclude that ultrasound and UGFNAB are of considerable value in staging head and neck malignancies.     

The Impact of Migraine on Health Status

Problems.-What is the effect of migraine on health status, defined as the patient's physical, psychological, and social functioning? And, suppose that the health status of migraine sufferers appears to be impaired, to what extent is this a consequence of migraine-associated comorbidity rather than of migraine itself? Methods.-A group of 846 migraineurs, selected from the general population following IHS criteria, and a control group were surveyed with the Medical Outcomes Study 36-item Short-Form Health Survey, Nottingham Health Profile, EuroQol instrument, end the COOP/WONCA charts. Questions on demographic characteristics and comorbidity were included. Results.-The health status of migraineurs appeared to be significantly impaired in comparison to the control group. Because statistical significance is distinct from relevance, effect size estimators were employed. Although the direction of the differences indicated consistently a worse health status of the migraineurs, regardless of the instrument used, the sizes of the differences were small to medium. Self-reported comorbidity, especially depression, was more prevalent in the migraine group. However, this offered only a partial explanation for the impaired health status of the migraine group. Conclusions.-Migraine has an independent moderately deteriorating effect on the daily functioning of individuals.     

Giant esophageal polyp: a clinical and radiological entity with variable histology

Giant pedunculated esophageal polyps are very rare. They may stay asymptomatic for a long time, and first come to the attention of the patient and the clinician after regurgitation into the mouth. Regurgitation, however, can be dangerous and has been known to lead to asphyxia and death due to closure of the larynx by the polyp mass. For this reason resection of the giant polyp is essential when it is discovered. We have seen four cases of giant esophageal polyps (GEP) at our institution. All four patients have undergone removal of the giant polyps. The histological diagnoses were fibrovascular polyp, liposarcoma, hamartoma and multiple lipomas. The mode of clinical presentation, radiological appearances, variable histological diagnoses, and therapy options in these four patients are presented along with a review of the literature. Received 4 March 1997; Revision received 13 June 1997; Accepted 15 July 1997