Login / Signup

Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism.

Rie SeyamaYuri UchiyamaYosuke KaneshiKohei HamanakaAtsushi FujitaNaomi TsuchidaEriko KoshimizuKazuharu MisawaSatoko MiyatakeTakeshi MizuguchiShintaro MakinoAtsuo ItakuraNobuhiko OkamotoNaomichi Matsumoto
Published in: Journal of human genetics (2023)
TNNI2 at 11p15.5 encodes troponin I2, fast skeletal type, which is a member of the troponin I gene family and a component of the troponin complex. Distal arthrogryposis (DA) is characterized by congenital limb contractures without primary neurological or muscular effects. DA is inherited in an autosomal dominant fashion and is clinically and genetically heterogeneous. Exome sequencing identified a causative variant in TNNI2 [NM_003282.4:c.532T>C p.(Phe178Leu)] in a Japanese girl with typical DA2b. Interestingly, the familial study using Sanger sequencing suggested a mosaic variant in her healthy father. Subsequent targeted amplicon-based deep sequencing detected the TNNI2 variant with variant allele frequencies of 9.4-17.7% in genomic DNA derived from peripheral blood leukocytes, saliva, hair, and nails in the father. We confirmed a disease-causing variant in TNNI2 in the proband inherited from her asymptomatic father with its somatic variant. Our case demonstrates that careful clinical and genetic evaluation is required in DA.
Keyphrases
  • peripheral blood
  • copy number
  • early onset
  • cancer therapy
  • single molecule
  • drug delivery
  • body composition
  • subarachnoid hemorrhage