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. 2020 Sep 18:7:26.
doi: 10.1038/s41439-020-00114-w. eCollection 2020.

Nonsense variants of STAG2 result in distinct congenital anomalies

Hiromi Aoi  1   2 , Ming Lei  1 , Takeshi Mizuguchi  1 , Nobuko Nishioka  3 , Tomohide Goto  4 , Sahoko Miyama  5 , Toshifumi Suzuki  2 , Kazuhiro Iwama  1 , Yuri Uchiyama  1 , Satomi Mitsuhashi  1 , Atsuo Itakura  2 , Satoru Takeda  2 , Naomichi Matsumoto  1
Affiliations

Nonsense variants of STAG2 result in distinct congenital anomalies

Hiromi Aoi et al. Hum Genome Var. .

Abstract

Herein, we report two female cases with novel nonsense mutations of STAG2 at Xq25, encoding stromal antigen 2, a component of the cohesion complex. Exome analysis identified c.3097 C>T, p.(Arg1033*) in Case 1 (a fetus with multiple congenital anomalies) and c.2229 G>A, p.(Trp743*) in Case 2 (a 7-year-old girl with white matter hypoplasia and cleft palate). X inactivation was highly skewed in both cases.

Keywords: Disease genetics; Next-generation sequencing.

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Conflict of interest statement

Conflict of interestThe authors declare that they have no conflict of interest.

Figures

Fig. 1
Fig. 1. Summary of pathogenic variants of STAG2.
a Familial pedigrees and electropherograms of STAG2 variants [Case 1: c.3097 C>T: p.(Arg1033*), Case 2: c.2229 G>A, (p.Trp743*)]. The arrow indicates a heterozygous variant. wt, wild-type; mut, mutation. b Functional domain of the STAG2 protein and pathogenic variants. Truncating and missense variants are shown above and below the protein, respectively. Our cases are shown in bold. The STAG domain predicted by Pfam is shown (http://pfam.xfam.org).
Fig. 2
Fig. 2. Confirmation of the pathogenic STAG2 variant in the paternal chromosome in Case 1.
a The c.3097 C>T variant could be successfully mapped within the 450-kb phased haplotype block in Case 1 using HiFi sequence and haplotype phasing. b SNP typing confirmed that the mutation occurred in the paternal chromosome (Allele 2, the brown haplotype block in Fig. 2a). POS: position of sequence, Pt: patient, Fa: father, Mo: mother.
See this image and copyright information in PMC

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