NOTCH3 – Infantile Myofibromatosis

In a cohort of nine unrelated families with autosomal dominant infantile myofibromatosis, whole-exome sequencing identified PDGFRB mutations in eight pedigrees and a single heterozygous NOTCH3 c.4556T>C (p.Leu1519Pro) segregating with disease in the remaining family (PMID:23731542). The missense change occurs in the extracellular domain of NOTCH3 and was present in all affected individuals across two generations, consistent with an autosomal dominant inheritance pattern.

No functional assays have assessed the behavior of NOTCH3 variants in infantile myofibromatosis, and mechanisms underlying mesenchymal tumorigenesis remain uncharacterized. Further genetic and experimental studies are required to substantiate the pathogenic role of NOTCH3 c.4556T>C (p.Leu1519Pro) in infantile myofibromatosis.

Key Take-home: NOTCH3 c.4556T>C (p.Leu1519Pro) is a candidate pathogenic variant in autosomal dominant infantile myofibromatosis, meriting additional evidence for clinical implementation.

References

• American journal of human genetics • 2013 • Mutations in PDGFRB cause autosomal-dominant infantile myofibromatosis. PMID:23731542

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