TRAPPC9-related neurodevelopmental disorder: Report of a homozygous deletion in TRAPPC9 due to paternal uniparental isodisomy.
Monica Penon-PortmannUgur HodoglugilWiita Arun PTiffany YipAnne M SlavotinekJessica L TenneyPublished in: American journal of medical genetics. Part A (2022)
TRAPPC9 loss-of-function biallelic variants are associated with an autosomal recessive intellectual disability syndrome (Online Mendelian Inheritance of Man no. 613192), also characterized by microcephaly, hypertelorism, obesity, growth delay, and behavioral differences. Here, we describe an 8-year-old Hispanic female with neurodevelopmental disorder, partial epilepsy, microcephaly, bilateral cleft lip and alveolus, growth delay, and dysmorphic features. She had abnormal myelination, mega cisterna magna, and colpocephaly on brain magnetic resonance imaging (MRI). Microarray showed a single ~146 Mb region of homozygosity (ROH) encompassing all of Chromosome 8, consistent with uniparental isodisomy (UPD). Exome sequencing performed in-house did not identify single nucleotide variants to explain her phenotype. Algorithms developed in-house and further evaluation of BAM files revealed a homozygous deletion overlapping Exon 2 in TRAPPC9 within the ROH. Subsequent del/dup analyses with exon-level oligo array confirmed a likely pathogenic deletion in TRAPPC9 (NM_031466.5): arr[GRCh37] 8q24.3(141460661_141461780)x0. Our case highlights the implications of downstream analyses from UPD/ROH given the increased risk for AR conditions, the strengths of combining orthologous molecular methods to establish a diagnosis and further delineates the TRAPPC9-related phenotype in an individual of Hispanic ancestry.
Keyphrases
- intellectual disability
- autism spectrum disorder
- magnetic resonance imaging
- copy number
- mitochondrial dna
- contrast enhanced
- single cell
- type diabetes
- machine learning
- computed tomography
- zika virus
- case report
- high throughput
- weight loss
- african american
- photodynamic therapy
- white matter
- resting state
- gene expression
- deep learning
- body mass index
- physical activity
- weight gain
- genome wide
- multiple sclerosis
- diffusion weighted imaging
- functional connectivity
- high resolution
- health information
- subarachnoid hemorrhage
- single molecule
- cerebral ischemia