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De novo AFF3 variant in a patient with mesomelic dysplasia with foot malformation.

Daisuke ShimizuRieko SakamotoKaori YamotoHirotomo SaitsuMaki FukamiGen NishimuraTsutomu Ogata
Published in: Journal of human genetics (2019)
Mesomelic dysplasia (MD) encompasses a heterogeneous group of disorders characterized by shortening of the middle segments of the limbs. Previous studies have revealed the development of Nievergelt type-like MD accompanied by postaxial toe reduction in a patient with a ~500 kb microdeletion at 2q11.2 involving AFF3 alone, and the occurrence of Nievergelt type-like MD in mice with a ~353 kb deletion involving Aff3, together with strong expression of mouse Aff3 in the developing limbs and zeugopod. We encountered a 2 6/12-year-old Japanese girl with an unclassifiable MD associated with hypoplasia of postaxial toes, and identified a de novo likely pathogenic variant of AFF3 (NM_002285.2:c.697 G > A, p.(Ala233Thr)) by whole exome sequencing. The results provide further evidence for AFF3 being the causative gene for MD with foot malformation which may be termed "AFF3-related MD" or "Steichen-Gersdorf type MD".
Keyphrases
  • molecular dynamics
  • case report
  • poor prognosis
  • risk assessment
  • gene expression
  • dna methylation
  • skeletal muscle
  • transcription factor
  • copy number
  • long non coding rna
  • drug induced