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A Novel Locus and Candidate Gene for Familial Developmental Dyslexia on Chromosome 4q
- Source :
- Zeitschrift fur Kinder-und Jugendpsychiatrie und Psychotherapie
- Publication Year :
- 2020
-
Abstract
- Objective: Developmental dyslexia is a highly heritable specific reading and writing disability. To identify a possible new locus and candidate gene for this disability, we investigated a four-generation pedigree where transmission of dyslexia is consistent with an autosomal dominant inheritance pattern. Methods: We performed genome wide array-based SNP genotyping and parametric linkage analysis and sequencing analysis of protein-coding exons, exon-intron boundaries and conserved extragenic regions within the haplotype cosegregating with dyslexia in DNA from one affected and one unaffected family member. Cosegregation was confirmed by sequencing all available family members. Additionally, we analyzed 96 dyslexic individuals who had previously shown positive LOD scores on chromosome 4q28 as well as an even larger sample ( n = 2591). Results: We found a single prominent linkage interval on chromosome 4q, where sequence analysis revealed a nucleotide variant in the 3’ UTR of brain expressed SPRY1 in the dyslexic family member that cosegregated with dyslexia. This sequence alteration might affect the binding efficiency of the IGF2BP1 RNA-binding protein and thus influence the expression level of the SPRY1 gene product. An analysis of 96 individuals from a cohort of dyslexic individuals revealed a second heterozygous variant in this gene, which was absent in the unaffected sister of the proband. An investigation of the region in a much larger sample further found a nominal p-value of 0.0016 for verbal short-term memory (digit span) in 2,591 individuals for a neighboring SNV. After correcting for the local number of analyzed SNVs, and after taking into account linkage disequilibrium, we found this corresponds to a p-value of 0.0678 for this phenotype. Conclusions: We describe a new locus for familial dyslexia and discuss the possibility that SPRY1 might play a role in the etiology of a monogenic form of dyslexia.
- Subjects :
- Proband
Candidate gene
Reading disability
Linkage disequilibrium
Locus (genetics)
Biology
Dyslexia
03 medical and health sciences
0302 clinical medicine
Genetic linkage
medicine
Humans
3' Untranslated Regions
030304 developmental biology
Genetics
Family Health
0303 health sciences
Haplotype
Membrane Proteins
RNA-Binding Proteins
General Medicine
medicine.disease
Phosphoproteins
Pedigree
Psychiatry and Mental health
Clinical Psychology
Pediatrics, Perinatology and Child Health
Chromosomes, Human, Pair 4
Lod Score
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 14224917
- Volume :
- 48
- Issue :
- 6
- Database :
- OpenAIRE
- Journal :
- Zeitschrift fur Kinder- und Jugendpsychiatrie und Psychotherapie
- Accession number :
- edsair.doi.dedup.....de5ab2e836d55caa0816482ef91ec311