Congenital arhinia, complete absence of the nose, is an extremely rare anomaly with unknown cause. To our knowledge, a total of 36 cases have been reported, but there has been no molecular-genetic study on this anomaly. We encountered a sporadic case of congenital arhinia associated with a de novo chromosomal translocation, t(3;12)(q13.2;p11.2). This led us to analyze the patient by BAC-based FISH for translocation breakpoints and whole-genome array CGH for other possible deletions/duplications in the genome. We found in this patient an approximately 19 Mb deletion spanning from 3q11.2 to 3q13.31 but no disruption of any gene(s) at the other breakpoint, 12p11.2. As the deleted segment at 3q was a strong candidate region containing the putative arhinia gene, we also performed the array CGH in four other arhinia patients with normal karyotypes, as well as mutation analysis of two genes, COL8A1 and CPOX, selected among hundreds of genes located to the deleted region, because they are expressed during early stages of human craniofacial development. However, in the four patients, there were no copy number aberrations in the region examined or no mutations in the two genes. Although our study failed to identify the putative arhinia gene, the data may become a clue to unravel the underlying mechanism of arhinia.

We report on a four-generation family with localized subepidermal telangiectasias following Blaschko's lines (angioma serpiginosum). The vascular streaks are present at birth and progress slowly thereafter. In several family members papillomatosis of the entire oesophagus was found to be part of the condition. Mild nail and hair dystrophy added to the resemblance of Goltz -Gorlin syndrome (focal dermal hypoplasia), suggesting that the present condition could be a mild variant. All affected family members are females, there is no increased miscarriage rate, and X-inactivation in affected females is highly skewed, compatible with X-linked dominant inheritance with very early in utero lethality in males. In the family, 11 informative meioses were available to study the segregation of X-chromosome markers. Significant linkage (LOD score 3.31) was found to a region flanked by markers DXS8026 and DXS106 (44 -67 Mb from Xpter) that includes the centromere.

We have investigated the clinical usefulness of the activated protein C resistance (APCR)/factor V Leiden mutation (FVL) test by sending out questionnaires to all Norwegian physicians who ordered these tests from our publicly funded service laboratory during a 3-month period, and of whom 70% (267/383) responded. Indications for testing, patient follow-up, the use of APCR versus FVL tests and differences in practice between hospital doctors and GPs were examined. We found that 46% of the tests were predictive, ordered for risk assessment in healthy individuals with no previous history of venous thromboembolism (VTE). Among these, 42% of the tests were taken on the initiative of the patient and 24% were screening tests before prescription of oral contraceptives. In total, 54% of the tests were classified as diagnostic, among which 42% were ordered owing to a previous history of VTE and 22% to a history of brain stroke or myocardial infarction. The prevalence of FVL heterozygotes was not significantly different between the predictive and diagnostic test groups, that is, 26 and 20%, respectively. Only the predictive tests influenced patient follow-up. Here, the physician's advice to patients depended on the test result. In general, the clinical usefulness of APCR/FVL testing was low. Many tests were performed on unsubstantiated or vague indications. Furthermore, normal test results led to unwarranted refrain from giving advice about antithrombotic measures, leading to potential harm to the patient. INTRODUCTIONThe clinical utility of tests for common genetic variants associated with slightly increased risk for multi-factorial disorders such as type II diabetes 1 and atherosclerosis 2 has been questioned. 3 Among such tests, the currently most commonly used test is the activated protein C resistance (APCR) test or factor V Leiden mutation DNA (FVL) test. Clinical utility refers to the likelihood that a test will lead to improved outcome for the patient tested. 3 As the presence of APCR (measured by the second generation APCR assay) is almost always because of the FVL, these tests are equivalent in a population with high FVL mutation prevalence, regardless of the test being performed on the biochemical or DNA level. 4 Both tests identify heterozygotes and homozygotes for the FVL mutation. About 3-8% of subjects in Caucasian populations are heterozygous for the FVL mutation and B0.2% are FVL homozygous. 4 In our laboratory, FVL heterozygosity was found in 8.5% of anonymous blood samples from 200 healthy blood donors (unpublished data). The heterozygotes have a fivefold and the homozygotes an 18-fold increased relative risk for venous thromboembolism (VTE). 5,6 The risk for VTE is determined by several known genetic factors (for example, the FVL and factor II prothrombin 20210G4A mutations, protein C, protein S and antithrombin deficiency), as well as by age, obesity, immobility, anti-phospholipid antibodies, infections, malignancies and smoking.The annual incidence of VTE is about 1 per 1000 individuals, 7,8 which cor...

Ida W. Sørensen er ph.d. og lege i spesialisering i medisinsk genetikk ved Haukeland universitetssjukehus. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. TRINE PRESCOTT Trine Prescott er spesialist i medisinsk genetikk og i barnesykdommer og er overlege ved Sykehuset i Telemark. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. CECILIE F. RUSTAD Cecilie F. Rustad er spesialist i medisinsk genetikk og overlege ved Oslo universitetssykehus. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter. ELLEN Ø. BLINKENBERG Ellen Ø. Blinkenberg er spesialist i medisinsk genetikk og overlege ved Haukeland universitetssjukehus. Forfatteren har fylt ut ICMJE-skjemaet og oppgir ingen interessekonflikter.