(Epi)genetic and clinical characteristics in 84 patients with pseudohypoparathyroidism type 1B
Tatsuki Urakawa, Shinichiro Sano, Sayaka Kawashima, Akie Nakamura, Hirohito Shima, Motoki Ohta, Yuki Yamada, Ai Nishida, Hiromune Narusawa, Yoshiaki Ohtsu, Keiko Matsubara, Sumito Dateki, Yoshihiro Maruo, Maki Fukami, Tsutomu Ogata, Masayo Kagami- Endocrinology
- General Medicine
- Endocrinology, Diabetes and Metabolism
Abstract
Objective
Pseudohypoparathyroidism type 1B (PHP1B) caused by methylation defects of differentially methylated regions (DMRs) on the GNAS locus can be categorized into groups according to etiologies and methylation defect patterns of the DMRs. The aim of this study was to clarify the clinical characteristics in each group.
Design
Comprehensive molecular analyses consisting of methylation, copy number, and microsatellite analyses.
Methods
Eighty-four patients with PHP1B were included in this study. We classified them into five groups, namely, autosomal dominant inheritance-PHP1B (Group 1, G1), sporadic-PHP1B (G2), and atypical-PHP1B (G3-G5), based on the methylation defect patterns in four DMRs on the GNAS locus and etiologies and evaluated the clinical findings in each group and compared them among the groups.
Results
G2 had the youngest age and the highest serum intact parathyroid hormone levels among the five groups at the time of diagnosis. The most common symptoms at the time of diagnosis were tetany in G1, and seizures or loss of consciousness in G2. Albright’s hereditary osteodystrophy and PHP-suggestive features were most frequently observed in the G2 proband. Nine patients had neurodevelopmental disorders (NDs) consisting of mild to borderline intellectual disability and/or developmental delay. There were no significant correlations between the average methylation ratios of seven CpG sites in the GNAS-A/B:TSS-DMR and hormonal and biochemical findings.
Conclusion
This study revealed the differences in some clinical characteristics, particularly clinical features and ages at the time of diagnosis between G2 and other groups and detailed NDs observed in some patients with PHP1B.