Dataset Information

Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males.

ABSTRACT: BACKGROUND:The cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed "cohesinopathies." METHODS:Using clinical exome sequencing, we have previously identified three female cases with heterozygous STAG2 mutations and overlapping syndromic phenotypes. Subsequently, a familial missense variant was identified in five male family members. RESULTS:We now present the case of a 4-year-old male with developmental delay, failure to thrive, short stature, and polydactyly with a likely pathogenic STAG2 de novo missense hemizygous variant, c.3027A>T, p.Lys1009Asn. Furthermore, we compare the phenotypes of the four previously reported STAG2 variants with our case. CONCLUSION:We conclude that mutations in STAG2 cause a novel constellation of sex-specific cohesinopathy-related phenotypes and are furthermore, essential for neurodevelopment, human growth, and behavioral development.

SUBMITTER: Mullegama SV

PROVIDER: S-EPMC6393687 | biostudies-literature | 2019 Feb

REPOSITORIES: biostudies-literature

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Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males.

Mullegama Sureni V SV Klein Steven D SD Signer Rebecca H RH Vilain Eric E Martinez-Agosto Julian A JA

Molecular genetics & genomic medicine 20181116 2

<h4>Background</h4>The cohesin complex is a multi-subunit protein complex which regulates sister chromatid cohesion and separation during cellular division. In addition, this evolutionarily conserved protein complex plays an integral role in DNA replication, DNA repair, and the regulation of transcription. The core complex is composed of four subunits: RAD21, SMC1A, SMC3, and STAG1/2. Mutations in these proteins have been implicated in human developmental disorders collectively termed "cohesinop ...[more]

PMID: 30447054

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Project description:Objective:Although research on muscle dysmorphia (MD), a body dysmorphic disorder subtype, has recently increased, the causes and mechanisms underlying this disorder remain unclear. Results from studies examining disorders associated with body image suggest the involvement of self-schema in biasing attention toward specific body information. The present study examined whether individuals at higher risk of MD also display attentional biases toward specific types of body images. Methods:The validated Chinese version of the Muscle Appearance Satisfaction Scale was used to distinguish men at higher and lower risk of MD. Sixty-five adult Chinese men at higher (HRMD, n = 33) and lower risk of MD (LRMD, n = 32) performed a visual probe task. Initially, an image of a bodybuilder with either larger or smaller musculature was presented on one side of a central point, with a neutral image of a car exterior presented on the other side along the horizontal plane for 2,000 ms. The paired images were removed, and a visual target (a dot) was displayed in the location of one of the previously shown images. Participants were asked to indicate the location of the target, and their eye movements were recorded during the entire visual presentation. Participant reaction time and three eye movement measurements (gaze direction, first saccade latency, and first fixation duration) were recorded for use in determining attentional bias. Results:The HRMD group revealed biases in orienting and maintaining their attention on images of bodybuilders with larger musculatures. Participants in this group consequently had a shorter reaction time in identifying the target that appeared at the location in which an image of a bodybuilder with a larger musculature had been previously displayed. They also directed their initial gaze more frequently, had shorter saccade latency, and had longer first fixation duration on images of bodybuilders with larger musculatures (all p < .0001). In comparison, the LRMD group had longer reaction times, slower attention orientation toward body images, and shorter fixation duration for images of bodybuilders with larger musculatures (all p < .0001), indicating weaker or mixed responses. Discussion:Adult Chinese men at higher risk of MD displayed biases in orienting and maintaining their visual attention toward images of bodybuilders with larger musculatures, and these biases facilitated their information processing. These results suggest that development of MD may be due in part to attentional biases associated with established negative self-schema of specific body information. These findings provide insight into understanding and identifying the cognitive characteristics of MD in an Asian population.

Dataset Information

Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males.

Publications

Mutations in STAG2 cause an X-linked cohesinopathy associated with undergrowth, developmental delay, and dysmorphia: Expanding the phenotype in males.

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