A novel missense mutation, p.(R102W) in WNT7A causes Al-Awadi Raas-Rothschild syndrome in a fetus.

Al-Awadi-Raas-Rothschild syndrome (AARRS) is a rare autosomal recessive disorder which consists of severe malformations of the upper and lower limbs, abnormal genitalia and underdeveloped pelvis. Here, we present a fetus with severe limbs defects, including bilateral humeroradial synostosis, bilateral oligodactyly in hands, underdeveloped pelvis, short femora and tibiae, absence of fibulae, severely small feet, and absence of uterus. An autosomal recessively inherited novel mutation in WNT7A found in the fetus, c.304C > T, affects an evolutionarily well-conserved amino acid, causing the p.(R102W) missense change at protein level. The findings presented in this fetus are compatible with diagnosis of AARRS, expanding the mutational spectrum of limb malformations arising from defects in WNT7A.

Effects of thyrotrophin, thyroid hormones and thyroid antibodies on metabolic parameters in a euthyroid population with obesity.

OBJECTIVE: To investigate whether thyroid function in the euthyroid range and thyroid autoimmunity status would affect metabolic measures in individuals with obesity. DESIGN: Cross-sectional. PATIENTS: We retrospectively evaluated 5300 consecutive obese (BMI ≥30 kg/m(2) ) subjects attending the Obesity Outpatient Clinic. Subjects with overt or subclinical thyroid disease, diabetes mellitus, chronic disease or using any medication were excluded. After exclusion, 1275 euthyroid [TSH values >0·4 and <4·5 µIU/ml, free triiodothyronine (FT3), free thyroxine (FT4) in the normal reference range] obese subjects (aged 18-65 years) were eligible for the study. MEASUREMENTS: The physical and biochemical records of the subjects at first admission to the obesity outpatient clinic were examined. RESULTS: Eighty-three per cent (n = 1063) of the study population were women. Antithyroid peroxidase (anti-TPO) positivity was 14%, and antithyroglobulin (anti-TG) positivity was 15%. TSH was 1·8 µIU/ml (1·3-2·4) in antibody-negative subjects and 2·1 µIU/ml (1·4-2·9) in antibody-positive subjects. Neither TSH nor thyroid antibody positivity was associated with insulin resistance (IR) and atherogenic dyslipidaemia after adjustment for confounders. FT3 was positively associated with IR (P < 0·001) and atherogenic dyslipidaemia (P = 0·03); however, this association lost its significance after adjustment for age, gender and BMI. FT4 was negatively associated with IR and this association remained even after adjustment for confounders (P < 0·001). CONCLUSION: TSH and thyroid antibody positivity were not related with metabolic measures. Low-normal FT4 had an inverse association with HOMA-IR even after adjustment for confounders.

DNA damage is increased in lymphocytes of patients with metabolic syndrome.

We assessed DNA damage in patients with metabolic syndrome (MetS) by performing comet and micronucleus (MN) assays on peripheral blood lymphocyte cultures from study participants. 52 MetS patients and 35 age-matched healthy controls were evaluated for abdominal obesity, body-mass index (BMI), blood pressure, serum triglycerides, HbA1c, HDL-C, and fasting blood glucose levels. In addition, malondialdehyde (MDA) levels and activities of superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) were determined. Serum levels of triglycerides, HbA1c, fasting blood glucose and waist circumference, systolic blood pressure, diastolic blood pressure, and BMI of the subjects in the MetS group were significantly higher than those of the control group (for each, p<0.001). However, the mean level of HDL-C in the MetS group was lower than in the control group (p<0.001). In the study, the length of comet tails was significantly higher in the MetS patients (10.23±1.98, range 5.72-15.08) than in the controls (3.12±1.73, range 0.6-7.1) (p<0.001). MN frequency was also significantly increased in MetS patients (3.68±1.27 per 1000 cells) compared to that of the control group (1.81±0.84 per 1000 cells) (p<0.001). Micronucleated cell frequency and comet-tail length in subjects showed positive correlations with waist circumference, BMI, and plasma triglyceride levels (p<0.01) and negative correlations with HDL-C levels (p<0.01). Among the oxidative stress factors, MDA levels were significantly higher in MetS patients than in the controls. However, SOD and GSH-Px enzyme activities were significantly lower in the MetS group than in the controls. These findings suggest that patients with MetS have increased DNA damage and oxidative stress.