De novo variant in AMOTL1 in infant with cleft lip and palate, imperforate anus and dysmorphic features.
Jonathan RipsHagar Mor-ShakedSerkan ErdinShira Yanovsky-DaganSmadar Eventov-FriedmanTamar HarelPublished in: American journal of medical genetics. Part A (2020)
AMOTL1 belongs to the Motin family of proteins that are involved in organogenesis and tumorigenesis through regulation of cellular migration, tube formation, and angiogenesis. While involvement of all AMOTs in development or suppression of cancers is relatively well described, little is known about the congenital phenotype of pathogenic variants in these genes in humans. Recently, a heterozygous variant in AMOTL1 was published in association with orofacial clefts and cardiac abnormalities in an affected father and his daughter. However, studies in mice did not recapitulate the human phenotype and the case was summarized as inconclusive. We present a female infant with cleft lip and palate, imperforate anus and dysmorphic features, in whom trio exome sequencing revealed a de novo variant in AMOTL1 affecting a highly conserved amino acid (c.479C>T; p.[Pro160Leu]). Bioinformatic predictions and in silico modeling supported pathogenicity. This case reinforces the conjecture regarding the disruptive effect of pathogenic variants in AMOTL1 on organ formation in humans. Studies of additional families will reveal the full phenotypic spectrum associated with this multiple malformation syndrome.
Keyphrases
- copy number
- endothelial cells
- single cell
- genome wide
- amino acid
- case control
- early onset
- transcription factor
- dna methylation
- molecular docking
- gene expression
- case report
- vascular endothelial growth factor
- biofilm formation
- cystic fibrosis
- randomized controlled trial
- pseudomonas aeruginosa
- induced pluripotent stem cells
- high fat diet induced
- young adults
- anti inflammatory
- wild type
- disease virus