TRAPPC9-related neurodevelopmental disorder: Report of a homozygous deletion in TRAPPC9 due to paternal uniparental isodisomy.
TRAPPC9
cleft lip
intellectual disability
microcephaly
uniparental isodisomy
Journal
American journal of medical genetics. Part A
ISSN: 1552-4833
Titre abrégé: Am J Med Genet A
Pays: United States
ID NLM: 101235741
Informations de publication
Date de publication:
04 2023
04 2023
Historique:
revised:
24
10
2022
received:
06
08
2022
accepted:
11
12
2022
pubmed:
28
12
2022
medline:
15
3
2023
entrez:
27
12
2022
Statut:
ppublish
Résumé
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.
Identifiants
pubmed: 36574751
doi: 10.1002/ajmg.a.63100
doi:
Types de publication
Case Reports
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
1077-1082Subventions
Organisme : NHGRI NIH HHS
ID : U01HG009599
Pays : United States
Informations de copyright
© 2022 Wiley Periodicals LLC.
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