Mutations in CEP120 cause Joubert syndrome as well as complex ciliopathy phenotypes.

BACKGROUND: Ciliopathies are an extensive group of autosomal recessive or X-linked disorders with considerable genetic and clinical overlap, which collectively share multiple organ involvement and may result in lethal or viable phenotypes. In large numbers of cases the genetic defect remains yet to be determined. The aim of this study is to describe the mutational frequency and phenotypic spectrum of the CEP120 gene. METHODS: Exome sequencing was performed in 145 patients with Joubert syndrome (JS), including 15 children with oral-facial-digital syndrome type VI (OFDVI) and 21 Meckel syndrome (MKS) fetuses. Moreover, exome sequencing was performed in one fetus with tectocerebellar dysraphia with occipital encephalocele (TCDOE), molar tooth sign and additional skeletal abnormalities. As a parallel study, 346 probands with a phenotype consistent with JS or related ciliopathies underwent next-generation sequencing-based targeted sequencing of 120 previously described and candidate ciliopathy genes. RESULTS: We present six probands carrying nine distinct mutations (of which eight are novel) in the CEP120 gene, previously found mutated only in Jeune asphyxiating thoracic dystrophy (JATD). The CEP120-associated phenotype ranges from mild classical JS in four patients to more severe conditions in two fetuses, with overlapping features of distinct ciliopathies that include TCDOE, MKS, JATD and OFD syndromes. No obvious correlation is evident between the type or location of identified mutations and the ciliopathy phenotype. CONCLUSION: Our findings broaden the spectrum of phenotypes caused by CEP120 mutations that account for nearly 1% of patients with JS as well as for more complex ciliopathy phenotypes. The lack of clear genotype-phenotype correlation highlights the relevance of comprehensive genetic analyses in the diagnostics of ciliopathies.

Bilateral Mammary Tuberculosis Associated with a Borderline Ovarian Tumor.

BACKGROUND: Mammary tuberculosis is rare in the Western world. It has no defined clinical or imaging features, and has to be differentiated from breast cancer and an abscess. CASE REPORT: We present a case of mammary tuberculosis combined with borderline ovarian cancer. The bilateral breast tuberculosis was the first and only symptom of underlying tuberculosis with Ziehl-Neelsen-positive para-aortic lymph nodes. During further exploration, an asymptomatic pelvic mass was discovered, which appeared later to be a borderline ovarian tumor. The patient was treated with tuberculostatic therapy for 6 months, resulting in a complete regression of the breast lesions. She also underwent hysterectomy with bilateral salpingo-oophorectomy and lymph node dissection for her ovarian cancer. CONCLUSIONS: This case report emphasizes that breast tuberculosis should be included in the differential diagnosis of any atypical breast mass.

Knowledge of cervix cancer, human papilloma virus (HPV) and HPV vaccination at the moment of introduction of the vaccine in women in Belgium.

AIM: To test the knowledge of women, attending a gynecology clinic, on HPV, cervix cancer awareness and the knowledge and willingness to use HPV vaccine for themselves or their children. SETTING: Routine gynecological and obstetrical care with ambulatory service in a medium-sized general hospital in a small town in Belgium (Heilig Hart Hospital, Tienen). METHODS: Questionnaire to be filled out by 381 consecutive women while in the attendance room for consultation with one of the four gynecologists. Fisher T or Chi(2) were used as statistical methods. RESULTS: Knowledge about HPV as a cause of cervix cancer and the existence of a vaccine was roughly 50%. Women with lower education were more likely to know nothing about the cause of cervix cancer than women with higher education (54 versus 39%, P = 0.016). Half of the women were willing to accept the vaccine, whatever the cost price, and 40% required more information or refunding. Compared to women above 40, young age (25 years or less) was a risk factor for poor knowledge of HPV (P = 0.007), cervix cancer (P = 0.016) and the HPV vaccine (P = 0.07), regardless of a higher degree of education (79% postgraduate degree versus 43.4% in the 40+-year-old women, P = 0.006). Women with a daughter (64.7%) or a son (69.2%) were more inclined to vaccinate their daughter than women without children (46.3%, P < 0.0001). None of the women declined the vaccination because it was meant to protect against a sexually transmitted disease (STD). CONCLUSION: Upon introduction and marketing of the first HPV vaccine, only 50% of women attending a routine gynecology clinic were aware of the role of HPV in cervix cancer and the possibility of getting a vaccination against it. Unexpectedly, despite a high degree of education, young women seem to have a low awareness of cervix cancer, its cause and the preventive measures. Contrary to some women in the USA, Western European women are less likely to decline the HPV vaccine because it will protect them against STD. In Belgium, women who are childless or poorly educated and especially young women should be the targets of campaigns that motivate them to prevent HPV-induced cervix cancer.