Abstract
Mutations in the gene kyphoscoliosis peptidase (KY) are known to cause myofibrillar myopathy-7 and hereditary spastic paraplegia. We investigated the genetic cause of a complex neurological phenotype in a consanguineous Pakistani family with four affected members, manifesting lower limb spasticity and weakness, toe walking, pes equinovarus, and a speech disorder. Genome-wide linkage analysis with microsatellite markers delineated chromosome 3q22.2-q24 harboring the disease gene. Whole exome sequencing was performed for two subjects, identifying a homozygous 14-bp frameshift deletion NM_178554.6:c.842_855del; p(Val281GlyfsTer18) in KY. The variant segregated with the phenotype and was absent from public databases and 100 ethnically matched controls. We confirm a novel homozygous KY variant causing a complex neurological phenotype in this family. A review of previously reported KY variants suggests that variants in this gene can cause a spectrum of neurological phenotypes.
| Original language | English |
|---|---|
| Article number | 104031 |
| Journal | European Journal of Medical Genetics |
| Volume | 63 |
| Issue number | 11 |
| Pages (from-to) | 104031 |
| ISSN | 1769-7212 |
| DOIs | |
| Publication status | Published - 11.2020 |
Funding
We thank the family for participating in this research. We are grateful to Dr. Akbar Malik, and Huma Tariq for their help in the study. KRK receives a philanthropic grant from the Paul Ainsworth Family Foundation and a Working Group Co-Lead Award from the Michael J. Fox Foundation, Aligning Science Across Parkinson's (ASAP) initiative. KL is supported by German Research Foundation (DFG, grant LO1553/8-1 ). Whole exome sequencing was performed by Baylor-Hopkins Center for Mendelian Genomics. This research was supported by NHGRI grant 1U54HG006542 , and Higher Education Commission grant 2877 (SN).
Research Areas and Centers
- Research Area: Medical Genetics
