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  • Brief Communication
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Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism


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.

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We thank the patient and her family for their participation in this study. We would like to thank G. Nishimura for the radiography of the patient. We would also like to thank N. Watanabe, T. Miyama, M. Sato, S. Sugimoto, and K. Takabe for their technical assistance. This study was supported by the Japan Agency for Medical Research and Development [grant numbers JP22ek0109486, JP22ek0109549, JP22ek0109493], JSPS KAKENHI [grant numbers JP20K07907, JP20K08164, JP21K15907, JP20K17428, JP21K07869, JP20K16932], the Takeda Science Foundation, and the Ichiro Kanehara Foundation for the Promotion of Medical Science and Medical Care. We thank Carol Wilson, PhD, from Edanz ( for editing a draft of this manuscript.

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Correspondence to Naomichi Matsumoto.

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Seyama, R., Uchiyama, Y., Kaneshi, Y. et al. Distal arthrogryposis in a girl arising from a novel TNNI2 variant inherited from paternal somatic mosaicism. J Hum Genet 68, 363–367 (2023).

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