Unclassifiable short-rib thoracic dysplasia diagnosed using targeted gene panel sequencing

Erika Nakajima; Yuko Yokohama; Saori Sugiyama; Mio Taketazu; Kenrokuro Mitsube; Takahiro Yamada; Anna Hammarsjö; Giedre Grigelioniene; Gen Nishimura; Yoshio Makita

doi:10.1038/s41439-024-00302-y

Unclassifiable short-rib thoracic dysplasia diagnosed using targeted gene panel sequencing

Hum Genome Var. 2024 Dec 3;11(1):44. doi: 10.1038/s41439-024-00302-y.

Authors

Erika Nakajima¹, Yuko Yokohama², Saori Sugiyama¹, Mio Taketazu³, Kenrokuro Mitsube¹, Takahiro Yamada^{4

5}, Anna Hammarsjö^{6

7}, Giedre Grigelioniene^{6

7}, Gen Nishimura^{8

9}, Yoshio Makita¹⁰

Affiliations

¹ Department of Obstetrics and Gynecology, Asahikawa-Kosei General Hospital, 1-24-111, Ichijo-dori, Asahikawa, Hokkaido, Japan.
² Department of Perinatal Medical Center, Asahikawa Medical University Hospital, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, Japan. [email protected].
³ Department of Pediatrics, Asahikawa-Kosei General Hospital, 1-24-111, Ichijo-dori, Asahikawa, Hokkaido, Japan.
⁴ Division of Clinical Genetics, Hokkaido University Hospital, Sapporo, Japan.
⁵ Japan Skeletal Dysplasia Consortium, Tokyo, N14W5, Kita-ku, Sapporo, Hokkaido, Japan.
⁶ Department of Molecular Medicine and Surgery, Karolinska Institutet, Stockholm, Sweden.
⁷ Department of Clinical Genetics and Genomics, Karolinska University Hospital, Karolinska University Hospital, Gävlegatan 68, 171 76 Solna, Stockholm, Sweden.
⁸ Department of Radiology, Musashino-Yowakai Hospital, Tokyo, Japan.
⁹ Japan Skeletal Dysplasia Consortium, 2-1-33, Midorityo, Musashino, Tokyo, Japan.
¹⁰ Department of Genetic Counseling, Asahikawa Medical University Hospital, 2-1-1-1 Midorigaoka-Higashi, Asahikawa, Hokkaido, Japan.

Abstract

We report a case of a fetus with short-rib thoracic dysplasia (SRTD) with polydactyly that also presented with atypical severe acro-mesomelic ossification defects. Genetic analysis using massively parallel sequencing of a skeletal dysplasia panel revealed compound heterozygous variants in DYNC2H1. This clinical report highlights the challenges associated with diagnosing the diverse phenotypes in the SRTD group and emphasizes the importance of genetic surveillance with a targeted gene panel for accurate diagnosis.