Skewed X chromosome inactivation in girls and female adolescents with autoimmune thyroid disease.

OBJECTIVE: Skewed X chromosome inactivation (XCI) was associated with female predominance in adult autoimmune thyroid disease (ATD). In normal females, skewed XCI is increased with age. Whether early-onset skewed XCI is associated with childhood ATD remains unknown. This study aimed to determine XCI skewing in paediatric ATD. DESIGN, PATIENTS AND MEASUREMENTS: Ninety-one female ATD patients, aged 3-20 years and 57 age-matched, female controls were enrolled. XCI was analysed by enzymatic digestion of DNA with methylation-sensitive enzymes followed by PCR of the polymorphic CAG repeat in the androgen receptor gene. Skewed XCI was defined as having 80% or greater of the cells preferentially inactivated on the same X chromosome. XCI pattern of the enrolled patients and parental origin of the skewed XCI were determined. RESULTS: After exclusion of samples with homozygous CAG repeats, skewed XCI was analysed in 83 patients (57 Graves' disease and 26 Hashimoto thyroiditis) and 52 controls. There was an increased frequency of skewed XCI in ATD patients as compared with the controls (23% vs 8%, P = 0.022). Patients with Hashimoto thyroiditis had greater frequency of skewed XCI than patients with Graves' disease (38% vs 16%, P = 0.023). There were no differences in clinical parameters between patients with skewed and random XCI. Analysis of 7 patients with skewed XCI showed a preferential inactivation of paternal X chromosome in 6 patients (86%). CONCLUSIONS: Frequency of skewed XCI was increased in childhood ATD. This observation suggests a possible association of skewed XCI in the development of paediatric ATD.

Three-Decade Successive Establishment of Care for Women/Girls from Families with Haemophilia.

Objective: The study aimed to report a 3-decade successive establishment of care for women/girls from families with haemophilia. Methods: A retrospective analysis was conducted on 462 women/girls from 243 families from 1987 to 2021. Results: Combining phenotypic analysis of coagulation factor and genotypic analysis of either linkage analysis or mutation detection confirmed the status of all obligate haemophilia carriers (A118, B19). For potential carrier, 159 proven carriers (A130, B29) and 146 noncarrier status (A126, B20) were diagnosed except 20 potential carriers (A16, B4). Only 54 prenatal diagnoses were requested resulting in normal males (n = 21), males with haemophilia A (n = 12) and females with either normal or carrier status (n = 21). Additionally, 40 women/girls with haemophilia carrier received a diagnosis of severe haemophilia A with Turner's syndrome (n = 2) and mild haemophilia (A31, B7). The skewed X-chromosome inactivation of the nonmutant factor VIII/IX carrying X-chromosome of 8% (2/25) was found in mild haemophilia. Factor concentrate and desmopressin are prescribed for these affected women/girls. The response of women/girls with either haemophilia carrier or haemophilia was amazement with their religious beliefs and cultural acceptance. Conclusion: Appropriate care for women/girls from families with haemophilia concerning diagnosis and management of haemophilia and carrier has been successively established.

A Simple and Applicable Method for Human Platelet Lysate Preparation Using Citrate Blood.

OBJECTIVES: To determine and compare the platelet growth factors in human platelet lysate (HPL) prepared from citrated whole blood, with final centrifugations at 4oC and 25oC. METHODS: We collected specimens of citrated whole blood from 27 healthy volunteers. The platelet-rich plasma (PRP) was separated to prepare the HPL, which was further divided into 2 portions for the final centrifugation, at 4oC and 25oC, respectively. Platelet growth factors were measured and compared between the 2 groups. RESULTS: All platelet growth factors were higher than those in PRP prepared from citrated whole blood. Moreover, the final centrifugation at 25oC resulted in noninferiority of platelet-growth-factor level. CONCLUSION: This study provided a simple method for small-volume of HPL preparation using only 10-15 mL of citrated whole blood. Further, the entire process of centrifugation can be performed at room temperature of 25oC, which is more applicable than lower temperatures for other laboratories.