Screening for subtelomeric rearrangements in 210 patients with unexplained mental retardation using multiplex ligation dependent probe amplification (MLPA).

BACKGROUND: Subtelomeric rearrangements contribute to idiopathic mental retardation and human malformations, sometimes as distinct mental retardation syndromes. However, for most subtelomeric defects a characteristic clinical phenotype remains to be elucidated. OBJECTIVE: To screen for submicroscopic subtelomeric aberrations using multiplex ligation dependent probe amplification (MLPA). METHODS: 210 individuals with unexplained mental retardation were studied. A new set of subtelomeric probes, the SALSA P036 human telomere test kit, was used. RESULTS: A subtelomeric aberration was identified in 14 patients (6.7%) (10 deletions and four duplications). Five deletions were de novo; four were inherited from phenotypically normal parents, suggesting that these were polymorphisms. For one deletion, DNA samples of the parents were not available. Two de novo submicroscopic duplications were detected (dup 5qter, dup 12pter), while the other duplications (dup 18qter and dup 22qter) were inherited from phenotypically similarly affected parents. All clinically relevant aberrations (de novo or inherited from similarly affected parents) occurred in patients with a clinical score of >or=3 using an established checklist for subtelomeric rearrangements. Testing of patients with a clinical score of >or=3 increased the diagnostic yield twofold to 12.4%. Abnormalities with clinical relevance occurred in 6.3%, 5.1%, and 1.7% of mildly, moderately, and severely retarded patients, respectively, indicating that testing for subtelomeric aberrations among mildly retarded individuals is necessary. CONCLUSIONS: The value of MLPA is confirmed. Subtelomeric screening can be offered to all mentally retarded patients, although clinical preselection increases the percentage of chromosomal aberrations detected. Duplications may be a more common cause of mental retardation than has been appreciated.

Cyclic changes in the concentration of glucose and fructose in human cervical mucus.

OBJECTIVE: To determine a possible cyclic change in the concentration of glucose and fructose in the aqueous phase of human cervical mucus (CM). DESIGN: Concentrations of glucose and fructose were longitudinally determined in the aqueous phase of CM of normal cycling women using enzymatic techniques, modified for small quantities. SETTING: Patients visiting a fertility clinic were selected. PATIENTS: Nine healthy women with regular menstrual cycles of 28 +/- 3 days that appeared to be ovulatory, demonstrated by sonographic follicle immaging and serum progesterone (P) measurements. INTERVENTIONS: Cervical mucus samples were longitudinally collected preovulatory, postovulatory, and premenstrual in ovulatory cycles, monitored by ultrasound and blood estradiol and P measurements. MAIN OUTCOME MEASURES: The study was designed to measure glucose and fructose longitudinally on three different points during one cycle. RESULTS: The preovulatory glucose concentrations in CM were lower than postovulatory and premenstrual. The preovulatory fructose concentrations were lower than premenstrual. The glucose concentration correlated with the blood P level. CONCLUSION: There is a consistent change in the glucose concentration measured in human CM in three phases of the menstrual cycle. The preovulatory and premenstrual fructose concentrations differ significantly. Knowledge of the carbohydrate metabolism in human cervical mucus may contribute in illuminating the possible role of the carbohydrate metabolism in sperm migration at midcycle and implantation in the luteal phase.