Guidelines for the genetic diagnosis of hereditary recurrent fevers.

Hereditary recurrent fevers (HRFs) are a group of monogenic autoinflammatory diseases characterised by recurrent bouts of fever and serosal inflammation that are caused by pathogenic variants in genes important for the regulation of innate immunity. Discovery of the molecular defects responsible for these diseases has initiated genetic diagnostics in many countries around the world, including the Middle East, Europe, USA, Japan and Australia. However, diverse testing methods and reporting practices are employed and there is a clear need for consensus guidelines for HRF genetic testing. Draft guidelines were prepared based on current practice deduced from previous HRF external quality assurance schemes and data from the literature. The draft document was disseminated through the European Molecular Genetics Quality Network for broader consultation and amendment. A workshop was held in Bruges (Belgium) on 18 and 19 September 2011 to ratify the draft and obtain a final consensus document. An agreed set of best practice guidelines was proposed for genetic diagnostic testing of HRFs, for reporting the genetic results and for defining their clinical significance.

Dopamine D4 receptor (D4DR) and serotonin transporter promoter (5-HTTLPR) polymorphisms in the determination of temperament in 2-month-old infants.

We and others have previously shown that the dopamine D4 exon III repeat (D4DR) and the serotonin-transporter promoter region (5-HTTLPR) polymorphisms are not only associated with adult personality traits1-7 but also with temperament in 2-week-old neonates.8 We now report the results of a second study of these infants and their temperament at 2 months using Rothbart's Infant Behavior Questionnaire (IBQ).9 There were significant negative correlations between neonatal orientation and motor organization as measured by the Neonatal Behavioral Assessment Scale (NBAS)10 at 2 weeks and negative emotionality, especially distress in daily situations, at 2 months of age. There were significant main effects for negative emotionality and distress when the infants were grouped by the D4DR and the 5-HTTLPR polymorphisms. Infants with long D4DR alleles had significantly lower scores on Negative Emotionality (F[1, 72] = 8.50, P = 0.005) and Distress to Limitations (F[1,72] = 4.93, P = 0.03) than infants with short D4DR alleles. In contrast, infants with the short homozygous (s/s) 5-HTTLPR genotype had higher scores on Negative Emotionality (F[1,72] = 3.88, P = 0.053) and Distress to Limitations (F[1,72] = 4.94, P = 0.029) than infants with the I/s or I/I genotypes. The strongest effects occurred in those infants with the s/s 5-HTTLPR polymorphism who also were lacking long D4DR alleles which in some studies has been linked to adult novelty seeking.1,6 These infants showed most negative emotionality and most distress to daily situations, temperament traits that are perhaps the underpinning of adult neuroticism.

Ritual female genital surgery among Ethiopian Jews.

Ritual female genital surgery is usually associated with Muslim countries although it is normative also among Ethiopian Coptic Christians. Ethiopian Jewish women immigrants to Israel report that ritual female genital surgery was normative in their culture in Ethiopia, but expressed no desire to continue the custom in Israel. This contrasts with Israeli Bedouin Muslims, who were reported to regard ritual female genital surgery as an important part of their identity. Physical examination of 113 Ethiopian Jewish immigrant women in Israel found a variety of lesions in about a third of women, with 27% showing total or partial clitoral amputation. The heterogeneity of the physical findings contrasts with uniform verbal reports in interviews of having undergone a ritual of female genital surgery.