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Implication of LRRC4C and DPP6 in neurodevelopmental disorders.
- Source :
-
American journal of medical genetics. Part A [Am J Med Genet A] 2017 Feb; Vol. 173 (2), pp. 395-406. Date of Electronic Publication: 2016 Oct 19. - Publication Year :
- 2017
-
Abstract
- We performed whole-genome sequencing on an individual from a family with variable psychiatric phenotypes that had a sensory processing disorder, apraxia, and autism. The proband harbored a maternally inherited balanced translocation (46,XY,t(11;14)(p12;p12)mat) that disrupted LRRC4C, a member of the highly specialized netrin G family of axon guidance molecules. The proband also inherited a paternally derived chromosomal inversion that disrupted DPP6, a potassium channel interacting protein. Copy Number (CN) analysis in 14,077 cases with neurodevelopmental disorders and 8,960 control subjects revealed that 60% of cases with exonic deletions in LRRC4C had a second clinically recognizable syndrome associated with variable clinical phenotypes, including 16p11.2, 1q44, and 2q33.1 CN syndromes, suggesting LRRC4C deletion variants may be modifiers of neurodevelopmental disorders. In vitro, functional assessments modeling patient deletions in LRRC4C suggest a negative regulatory role of these exons found in the untranslated region of LRRC4C, which has a single, terminal coding exon. These data suggest that the proband's autism may be due to the inheritance of disruptions in both DPP6 and LRRC4C, and may highlight the importance of the netrin G family and potassium channel interacting molecules in neurodevelopmental disorders. © 2016 Wiley Periodicals, Inc.<br /> (© 2016 Wiley Periodicals, Inc.)
- Subjects :
- 5' Untranslated Regions
Adolescent
Adult
Apraxias diagnosis
Apraxias genetics
Autistic Disorder diagnosis
Autistic Disorder genetics
Child
Child, Preschool
Chromosome Breakpoints
Chromosome Inversion
Comparative Genomic Hybridization
DNA Copy Number Variations
Female
Gene Expression
Gene Expression Profiling
High-Throughput Nucleotide Sequencing
Humans
Karyotype
Male
Middle Aged
Multigene Family
Pedigree
Translocation, Genetic
Young Adult
Dipeptidyl-Peptidases and Tripeptidyl-Peptidases genetics
Genetic Association Studies
Nerve Tissue Proteins genetics
Neurodevelopmental Disorders diagnosis
Neurodevelopmental Disorders genetics
Phenotype
Potassium Channels genetics
Receptors, Cell Surface genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1552-4833
- Volume :
- 173
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- American journal of medical genetics. Part A
- Publication Type :
- Academic Journal
- Accession number :
- 27759917
- Full Text :
- https://doi.org/10.1002/ajmg.a.38021