PUBLICATION
INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family
- Authors
- Yousaf, S., Sheikh, S.A., Riazuddin, S., Waryah, A.M., Ahmed, Z.M.
- ID
- ZDB-PUB-170924-3
- Date
- 2017
- Source
- Clinical genetics 93(3): 682-686 (Journal)
- Registered Authors
- Keywords
- Cataract, INPP5K, Muscular dysplasia, PtdIns, lens development
- MeSH Terms
-
- Adolescent
- Animals
- Cataract/congenital*
- Cataract/genetics
- Child
- Child, Preschool
- Computational Biology/methods
- Consanguinity
- Exome Sequencing
- Female
- Genes, Recessive*
- Genetic Variation*
- Humans
- Infant
- Loss of Function Mutation
- Magnetic Resonance Imaging
- Male
- Pakistan
- Pedigree
- Phenotype
- Phosphoric Monoester Hydrolases/chemistry
- Phosphoric Monoester Hydrolases/genetics*
- Zebrafish
- PubMed
- 28940338 Full text @ Clin. Genet.
Citation
Yousaf, S., Sheikh, S.A., Riazuddin, S., Waryah, A.M., Ahmed, Z.M. (2017) INPP5K variant causes autosomal recessive congenital cataract in a Pakistani family. Clinical genetics. 93(3):682-686.
Abstract
Congenital cataract (CC) is clinically and genetically highly heterogeneous. Here, we enrolled a consanguineous kindred (LUCC15) from Pakistan, with three affected individuals suffering with CC. Exome sequencing revealed a transition mutation [c.149T>C; p.(Ile50Thr)] in INPP5K. Inositol polyphosphate-5-phosphatase K, encoded by INPP5K, is involved in dephosphorylation of phosphatidylinositol (PtdIns) 4,5-bisphosphate, and PtdIns 3,4,5-trisphosphate. Recently, pathogenic variants in INPP5K have been reported in families with congenital muscular dystrophies, intellectual disability, and cataract. In our family LUCC15, mild to moderate intellectual disability along with speech impairment was observed in two affected individuals. Magnetic resonance imaging of brain and muscles tissues did not reveal any cerebellar or muscular atrophy. However, electromyography of both upper and lower limbs revealed irritable myopathy. Comparison of clinical phenotype of all the known affected individuals, including LUCC15 family, homozygous for INPP5K alleles revealed reduced penetrance of muscular dystrophy and intellectual disability. Similarly, skeletal muscle abnormalities were highly variable among inpp5ka zebrafish mutants analyzed in this study. These phenotypic variabilities may be due to epigenetic factors and/or genetic modifiers.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping