Guerreiro, R;
Brás, J;
Batista, S;
Pires, P;
Ribeiro, MH;
Almeida, MR;
Oliveira, C;
... Santana, I; + view all
(2016)
Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation.
Genes, Brain and Behaviour
, 15
(7)
pp. 669-677.
10.1111/gbb.12308.
Preview |
Text
Guerreiro_et_al-2016-Genes,_Brain_and_Behavior.pdf - Published Version Download (760kB) | Preview |
Abstract
Pseudohypoparathyroidism type 1b (PHP1b) is characterized by hypocalcemia, hyperphosphatemia, increased levels of circulating parathyroid hormone (PTH), and no skeletal or developmental abnormalities. The goal of this study was to perform a full characterization of a familial case of PHP1b with neurological involvement and to identify the genetic cause of disease. The initial laboratory profile of the proband showed severe hypocalcemia, hyperphosphatemia and normal levels of PTH, which was considered to be compatible with primary hypoparathyroidism. With disease progression the patient developed cognitive disturbance, PTH levels were found to be slightly elevated and a picture of PTH resistance syndrome seemed more probable. The diagnosis of PHP1b was established after the study of family members and blunted urinary cAMP results were obtained in a PTH stimulation test. Integration of whole genome genotyping and exome sequencing data supported this diagnosis by revealing a novel homozygous missense mutation in PTH1R (p.Arg186His) completely segregating with the disease. Here, we demonstrate segregation of a novel mutation in PTH1R with a phenotype of PHP1b presenting with neurological symptoms, but no bone defects. This case represents the extreme end of the spectrum of cognitive impairment in PTH dysfunction and defines a possible novel form of PHP1b resulting from the impaired interaction between PTH and PTH1R.
| Type: | Article |
|---|---|
| Title: | Pseudohypoparathyroidism type I-b with neurological involvement is associated with a homozygous PTH1R mutation |
| Location: | England |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1111/gbb.12308 |
| Publisher version: | http://dx.doi.org/10.1111/gbb.12308 |
| Language: | English |
| Additional information: | © 2016 The Authors. Genes, Brain and Behavior published by International Behavioural and Neural Genetics Society and John Wiley & Sons Ltd. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited. |
| Keywords: | Dementia, PTH1R, Pseudohypoparathyroidism Type I-b, exome sequencing |
| UCL classification: | UCL UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > Neurodegenerative Diseases |
| URI: | https://discovery-pp.ucl.ac.uk/id/eprint/1506198 |
Archive Staff Only
 |
View Item |
