PUBLICATION
A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism
- Authors
- Pillar, N., Pleniceanu, O., Fang, M., Ziv, L., Lahav, E., Botchan, S., Cheng, L., Dekel, B., Shomron, N.
- ID
- ZDB-PUB-170427-4
- Date
- 2017
- Source
- Human genetics 136(7): 835-845 (Journal)
- Registered Authors
- Ziv, Limor
- Keywords
- none
- MeSH Terms
-
- Animals
- Calcium/metabolism
- Exons
- Female
- Gene Expression Regulation
- Genomics
- HEK293 Cells
- Humans
- Hypercalciuria/diagnosis
- Hypercalciuria/genetics*
- Hypocalcemia/diagnosis
- Hypocalcemia/genetics*
- Hypoparathyroidism/congenital*
- Hypoparathyroidism/diagnosis
- Hypoparathyroidism/genetics
- Intracellular Signaling Peptides and Proteins/genetics*
- Intracellular Signaling Peptides and Proteins/metabolism
- LIM Domain Proteins/genetics*
- LIM Domain Proteins/metabolism
- Male
- Muscle Proteins/genetics*
- Muscle Proteins/metabolism
- Mutation
- Pedigree
- Zebrafish/genetics
- Zebrafish Proteins/genetics*
- Zebrafish Proteins/metabolism
- PubMed
- 28444561 Full text @ Hum. Genet.
Citation
Pillar, N., Pleniceanu, O., Fang, M., Ziv, L., Lahav, E., Botchan, S., Cheng, L., Dekel, B., Shomron, N. (2017) A rare variant in the FHL1 gene associated with X-linked recessive hypoparathyroidism. Human genetics. 136(7):835-845.
Abstract
Isolated familial hypoparathyroidism is an extremely rare disorder, which to date has been linked to several loci including mutations in CASR, GCM2, and PTH, as well as a rare condition defined as X-linked recessive hypoparathyroidism, previously associated with a 1.5 Mb region on Xq26-q27. Here, we report a patient with hypocalcemia-induced seizures leading to the diagnosis of primary hypoparathyroidism. Mutations in CASR, GCM2, and PTH were ruled out, while whole exome sequencing of the family suggested FHL1, located on chromosome Xq26, as the most likely causative gene variant (FHL1, exon 4, c.C283T, p.R95W). Since FHL1 has not been linked to calcium regulation before, we provide evidence for its functional role in hypoparathyroidism by: (i) bioinformatics analysis coupling its action to known modulators of PTH function; (ii) observing strong expression of fhl1b in Corpuscles of Stannius, gland-like aggregates in zebrafish that function in calcium regulation similar to mammalian PTH; and (iii) implicating fhl1b and FHL1 as regulators of calcium homeostasis in zebrafish and human cells, respectively. Altogether, our data suggest that FHL1 is a novel regulator of calcium homeostasis and implicate it as the causative gene for X-linked recessive hypoparathyroidism.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping