PUBLICATION
Point mutations in KAL1 and the mitochondrial gene MT-tRNA(cys) synergize to produce Kallmann syndrome phenotype
- Authors
- Wang, F., Huang, G.D., Tian, H., Zhong, Y.B., Shi, H.J., Li, Z., Zhang, X.S., Wang, H., Sun, F.
- ID
- ZDB-PUB-170214-134
- Date
- 2015
- Source
- Scientific Reports 5: 13050 (Journal)
- Registered Authors
- Huang, Guodong, Li, Zheng, Sun, Fei, Wang, Han, Zhong, Yingbin
- Keywords
- Disease genetics, Endocrine reproductive disorders, Genetics of the nervous system
- MeSH Terms
-
- Point Mutation
- HEK293 Cells
- Cell Movement
- RNA Interference
- Pedigree
- PubMed
- 26278626 Full text @ Sci. Rep.
Abstract
Kallmann syndrome (KS) is an inherited developmental disorder defined as the association of hypogonadotropic hypogonadism and anosmia or hyposmia. KS has been shown to be a genetically heterogeneous disease with different modes of inheritance. However, variants in any of the causative genes identified so far are only found in approximately one third of KS patients, thus indicating that other genes or pathways remain to be discovered. Here, we report a large Han Chinese family with inherited KS which harbors two novel variants, KAL1 c.146G>T (p.Cys49Phe) and mitochondrial tRNA(cys) (m.5800A>G). Although two variants can't exert obvious effects on the migration of GnRH neurons, they show the synergistic effect, which can account for the occurrence of the disorder in this family. Furthermore, the disturbance of the mitochondrial cysteinyl-tRNA pathway can significantly affect the migration of GnRH cells in vitro and in vivo by influencing the chemomigration function of anosmin-1. Our work highlights a new mode of inheritance underlay the genetic etiology of KS and provide valuable clues to understand the disease development.
Genes / Markers
Figure Gallery (1 images)
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping