Transcription factor SOX10 plays a role in the maintenance of progenitor cell multipotency, lineage specification, and cell differentiation and is a major actor in the development of the neural crest. It has been implicated in Waardenburg syndrome (WS), a rare disorder characterized by the association between pigmentation abnormalities and deafness, but SOX10 mutations cause a variable phenotype that spreads over the initial limits of the syndrome definition. On the basis of recent findings of olfactory-bulb agenesis in WS individuals, we suspected SOX10 was also involved in Kallmann syndrome (KS). KS is defined by the association between anosmia and hypogonadotropic hypogonadism due to incomplete migration of neuroendocrine gonadotropin-releasing hormone (GnRH) cells along the olfactory, vomeronasal, and terminal nerves. Mutations in any of the nine genes identified to date account for only 30% of the KS cases. KS can be either isolated or associated with a variety of other symptoms, including deafness. This study reports SOX10 loss-of-function mutations in approximately one-third of KS individuals with deafness, indicating a substantial involvement in this clinical condition. Study of SOX10-null mutant mice revealed a developmental role of SOX10 in a subpopulation of glial cells called olfactory ensheathing cells. These mice indeed showed an almost complete absence of these cells along the olfactory nerve pathway, as well as defasciculation and misrouting of the nerve fibers, impaired migration of GnRH cells, and disorganization of the olfactory nerve layer of the olfactory bulbs.

Considering the large prevalence and clinical spectrum of CHD7 mutations, it will be particularly relevant to genetic counseling to search for mutations in this gene in KS patients seeking fertility treatment, especially if KS is associated with deafness and cleft lip/palate.

This study suggested that the increased rate of adverse maternal and fetal outcome, especially LGA, was associated with untreated mild gestational hyperglycaemia women compared to a control group. This link to lower degrees of hyperglycaemia during pregnancy is independent of confounding factors.

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OBJECTIVE -To evaluate perinatal outcome in pregnancies in women with type 1 and type 2 diabetes and the influence of preconception care 10 years after the St. Vincent's declaration. RESEARCH DESIGN AND METHODS-A cross-sectional study was conducted in 12 perinatal centers in France in 2000 -2001. The main investigated outcomes were perinatal mortality, major congenital malformations, and preterm delivery.RESULTS -Among 435 single pregnancies, 289 (66.4%) were from women with type 1 and 146 (33.6%) from women with type 2 diabetes. Perinatal mortality rate was 4.4% (0.7% national rate), severe congenital malformations rate was 4.1% (2.2% national rate), and preterm delivery rate was 38.2% (4.7% national rate). Preconception care was provided in 48.5% women with type 1 diabetes and in 24.0% women with type 2 diabetes. Women whose first trimester HbA 1c was Ͼ8% had higher rates of perinatal mortality (9.2 vs. 2.5%; odds ratio 3.9; 95% CI 1.5-9.7; P Ͻ 0.005), major congenital malformations (8.3 vs. 2.5%; 3.5; 1.3-8.9; P Ͻ 0.01), and preterm delivery (57.6 vs. 24.8%; 1.4; 1.1-1.7; P Ͻ 0.005) than those with first trimester HbA 1c Ͻ8%. These results are similar to those reported in France in 1986 -1988.CONCLUSIONS -Pregnancies in women with diabetes are still poorly planned and complicated by higher rates of perinatal mortality and major congenital malformations. Despite knowledge of the importance of intensified glycemic control before pregnancy, reaching the St. Vincent's target needs further implementation in France. Diabetes Care 26:2990 -2993, 2003I n 1989, representatives of the government health departments and patients' organizations from all of the European countries met with diabetes experts under the aegis of the Regional Offices of the World Health Organization and the International Diabetes Federation in St. Vincent, Italy, and identified goals to be achieved in the treatment of diabetes (1). One of the declared aims was that within 5 years, "pregnancy outcome of diabetic women should approximate that of the nondiabetic women." Previous studies have shown that such results may be obtained in women with type 1 diabetes by providing effective preconception care and intensive support to improve glycemic control before and during the whole pregnancy (2-5). However, this was achieved in selected populations and in specialized units. By contrast, several surveys done in nonselected, geographically based populations showed that the prognosis of pregnancy in women with type 1 diabetes remains poorer than that of the general population (6,7). Moreover, new issues have been raised by the increasing prevalence of type 2 diabetes in pregnancy (8). Particularly, type 2 diabetes often remains unrecognized, and the rate of perinatal mortality in women with type 2 diabetes may be higher than in those with type 1 diabetes (9).In 1986 -1988, a multicenter survey of pregnancies in women with diabetes was performed in France (10). It essentially showed that the rate of perinatal mortality was 1.9% in women with type 1 diabete...