Pseudohypoparathyroidism type 1B caused by methylation changes at the GNAS complex locus.

Pseudohypoparathyroidism type 1B (PHP1B) consists of a heterogeneous group of disorders characterised by resistance to parathyroid hormone (PTH). There are several different PHP1B subtypes that are all associated with methylation changes at GNAS. These epigenetic changes are caused by maternal deletions in GNAS or STX16, by paternal uniparental isodisomy of chromosome 20q (patUPD20q) or by undefined genetic mutations. The GNAS methylation changes are ultimately responsible for resistance to PTH signalling in the proximal renal tubules. However, there is no PTH resistance in the distal renal tubules nor in bone cells; consequently, patients with PHP1B have reduced urinary calcium excretion and can readily mobilise calcium (and phosphate) from the skeleton. We report a case of a sporadic PHP1B patient with broad GNAS methylation changes that were presumably caused by an unknown genetic mutation outside the GNAS locus. PTH resistance was preceded by several years by autoimmune negative hypothyroidism. Treatment consisted of calcium substitution and calcitriol.

Quantification of bacterial species of the vaginal microbiome in different groups of women, using nucleic acid amplification tests.

BACKGROUND: The vaginal microbiome plays an important role in urogenital health. Quantitative real time Polymerase Chain Reaction (qPCR) assays for the most prevalent vaginal Lactobacillus species and bacterial vaginosis species G. vaginalis and A. vaginae exist, but qPCR information regarding variation over time is still very limited. We set up qPCR assays for a selection of seven species and defined the temporal variation over three menstrual cycles in a healthy Caucasian population with a normal Nugent score. We also explored differences in qPCR data between these healthy women and an 'at risk' clinic population of Caucasian, African and Asian women with and without bacterial vaginosis (BV), as defined by the Nugent score. RESULTS: Temporal stability of the Lactobacillus species counts was high with L. crispatus counts of 108 copies/mL and L. vaginalis counts of 106 copies/mL. We identified 2 types of 'normal flora' and one 'BV type flora' with latent class analysis on the combined data of all women. The first group was particularly common in women with a normal Nugent score and was characterized by a high frequency of L. crispatus, L. iners, L. jensenii, and L. vaginalis and a correspondingly low frequency of L. gasseri and A. vaginae. The second group was characterized by the predominance of L. gasseri and L. vaginalis and was found most commonly in healthy Caucasian women. The third group was commonest in women with a high Nugent score but was also seen in a subset of African and Asian women with a low Nugent score and was characterized by the absence of Lactobacillus species (except for L. iners) but the presence of G. vaginalis and A. vaginae. CONCLUSIONS: We have shown that the quantification of specific bacteria by qPCR contributes to a better description of the non-BV vaginal microbiome, but we also demonstrated that differences in populations such as risk and ethnicity also have to be taken into account. We believe that our selection of indicator organisms represents a feasible strategy for the assessment of the vaginal microbiome and could be useful for monitoring the microbiome in safety trials of vaginal products.