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


Journal

Journal of human genetics
ISSN: 1435-232X
Titre abrégé: J Hum Genet
Pays: England
ID NLM: 9808008

Informations de publication

Date de publication:
May 2023
Historique:
received: 05 10 2022
accepted: 25 12 2022
revised: 22 12 2022
medline: 26 4 2023
pubmed: 12 1 2023
entrez: 11 1 2023
Statut: ppublish

Résumé

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.

Identifiants

pubmed: 36631501
doi: 10.1038/s10038-022-01117-x
pii: 10.1038/s10038-022-01117-x
doi:

Substances chimiques

Troponin I 0
TNNI2 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

363-367

Subventions

Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP22ek0109486
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP22ek0109549
Organisme : Japan Agency for Medical Research and Development (AMED)
ID : JP22ek0109493

Informations de copyright

© 2023. The Author(s), under exclusive licence to The Japan Society of Human Genetics.

Références

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Auteurs

Rie Seyama (R)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan.

Yuri Uchiyama (Y)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.

Yosuke Kaneshi (Y)

Department of Pediatrics, Kushiro Red Cross Hospital, Kushiro, Japan.

Kohei Hamanaka (K)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Atsushi Fujita (A)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Naomi Tsuchida (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Rare Disease Genomics, Yokohama City University Hospital, Yokohama, Japan.

Eriko Koshimizu (E)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Kazuharu Misawa (K)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
RIKEN Center for Advanced Intelligence Project, Tokyo, Japan.

Satoko Miyatake (S)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.
Department of Clinical Genetics, Yokohama City University Hospital, Yokohama, Japan.

Takeshi Mizuguchi (T)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan.

Shintaro Makino (S)

Department of Obstetrics and Gynecology, Juntendo University Urayasu Hospital, Urayasu, Japan.

Atsuo Itakura (A)

Department of Obstetrics and Gynecology, Juntendo University, Tokyo, Japan.

Nobuhiko Okamoto (N)

Department of Medical Genetics, Osaka Women's and Children's Hospital, Izumi, Osaka, Japan.

Naomichi Matsumoto (N)

Department of Human Genetics, Yokohama City University Graduate School of Medicine, Yokohama, Japan. naomat@yokohama-cu.ac.jp.

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