A <i>MID1</i> gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain

Hu, Ching-Hsuan; Liu, Yu-Fan; Yu, Ju-Shan; Ng, Yan-Yan; Chen, Suh-Jen; Su, Pen‐Hua; Chen, Jia-Yuh

doi:10.1002/ajmg.a.35216

Cited by 15 publications

(10 citation statements)

References 29 publications

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“…B. Summary of all reported mutations, to date, of MID1 and the associated anomalies [27], [28], [29], [30], [31], [32], [33], [34]. The four types of mutations observed are color-coded (red = point mutation, blue = frame shifts, magenta = termination/truncation, and black = deletion).…”

Section: Introductionmentioning

confidence: 99%

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MID1 Catalyzes the Ubiquitination of Protein Phosphatase 2A and Mutations within Its Bbox1 Domain Disrupt Polyubiquitination of Alpha4 but Not of PP2Ac

Didoronkute

et al. 2014

PLoS ONE

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MID1 is a microtubule-associated protein that belongs to the TRIM family. MID1 functions as an ubiquitin E3 ligase, and recently was shown to catalyze the polyubiquitination of, alpha4, a protein regulator of protein phosphatase 2A (PP2A). It has been hypothesized that MID1 regulates PP2A, requiring the intermediary interaction with alpha4. Here we report that MID1 catalyzes the in vitro ubiquitination of the catalytic subunit of PP2A (PP2Ac) in the absence of alpha4. In the presence of alpha4, the level of PP2Ac ubiquitination is reduced. Using the MID1 RING-Bbox1-Bbox2 (RB1B2) construct containing the E3 ligase domains, we investigate the functional effects of mutations within the Bbox domains that are identified in patients with X-linked Opitz G syndrome (XLOS). The RB1B2 proteins harboring the C142S, C145T, A130V/T mutations within the Bbox1 domain and C195F mutation within the Bbox2 domain maintain auto-polyubiquitination activity. Qualitatively, the RB1B2 proteins containing these mutations are able to catalyze the ubiquitination of PP2Ac. In contrast, the RB1B2 proteins with mutations within the Bbox1 domain are unable to catalyze the polyubiquitination of alpha4. These results suggest that unregulated alpha4 may be the direct consequence of these natural mutations in the Bbox1 domain of MID1, and hence alpha4 could play a greater role to account for the increased amount of PP2A observed in XLOS-derived fibroblasts.

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Section: Introductionmentioning

confidence: 99%

“…In the past decade, there have been numerous reports identifying mutations of MID1 from individuals with ventral midline anomalies that affect the brain, face, heart and genitalia (Figure 1B) [27], [28], [29], [30], [31], [32], [33], [34]. Individuals with these defects are diagnosed with X-linked Opitz G Syndrome (XLOS).…”

Section: Introductionmentioning

confidence: 99%

MID1 Catalyzes the Ubiquitination of Protein Phosphatase 2A and Mutations within Its Bbox1 Domain Disrupt Polyubiquitination of Alpha4 but Not of PP2Ac

Didoronkute

et al. 2014

PLoS ONE

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“…To date, 90 different pathogenic variants in MID1 have been described, including missense and nonsense mutations, small insertions and deletions, splice site alterations, exon deletions and duplications as well as deletions of the complete gene [Quaderi et al, 1997;Gaudenz et al, 1998;Schweiger et al, 1999;Cox et al, 2000;De Falco et al, 2003;Winter et al, 2003;Pinson et al, 2004;So et al, 2005;Cho et al, 2006;Mnayer et al, 2006;Shaw et al, 2006;Ferrentino et al, 2007;Fontanella et al, 2008;Hsieh et al, 2008;Taylor and Aftimos, 2010;Ruiter et al, 2010;Zhang et al, 2011;Hu et al, 2012;Huning et al, 2013;Migliore et al, 2013;Ji et al, 2014;Preiksaitiene et al, 2015]. MID1 consists of the RING finger (RING), zinc-binding B-box-1 (B1) and B-box-2 (B2) domains, followed by a coiled-coil region (CC) and C-terminal subgroup one signature (COS), fibronectin type III repeat (FN3) and PRY-SPRY domains [Quaderi et al, 1997;Du et al, 2014].…”

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confidence: 99%

Two Novel Pathogenic MID1 Variants and Genotype-Phenotype Correlation Reanalysis in X-Linked Opitz G/BBB Syndrome

Maia¹,

Sá

Tkachenko

et al. 2017

Mol Syndromol

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X-linked Opitz G/BBB syndrome (XLOS) is a multisystemic congenital condition, caused by mutations in the midline-1 gene (MID1), characterized by a large inter- and intrafamilial phenotypic variability and often associated with intellectual disability (ID). We report clinical, genetic, and molecular findings in 4 patients with typical XLOS dysmorphic features belonging to 2 unrelated families. Two novel pathogenic loss-of-function MID1 variants, a maternally inherited c.1656del and a de novo c.1215_1228dup, were identified. Subsequently, we performed a genotype-phenotype analysis using data from 91 male XLOS patients. To test the mutation impact on the phenotype; the type of mutation, the MID1-impaired domain and function were compared with the presence of each of the major clinical features (hypertelorism, clefts of the lip and/or palate, laryngo-tracheo-esophageal abnormalities, hypospadias and ID ) and minor clinical features (brain, heart, and anal defects). No statistically significant correlation was found with these features. Further investigations, as well as exhaustive and unequivocal phenotyping, may be required to improve our knowledge of the biological mechanisms underlying this syndrome and to provide more adequate disease management.

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“…Structural abnormalities of the central nervous system (CNS) have occasionally been reported in patients with Opitz syndrome, which include inversion and left hippocampus dilatation of the temporal horn ipsilateral normal and corpus callosum, hypoplasia of the corpus callosum, and cerebellar hypoplasia . In individuals identified with mutation in MiD1, their brain MRI show midline malformations in 40% of the cases, and agenesis or hypoplasia of the corpus callosum and/or cerebellar vermis …”

Section: Introductionmentioning

confidence: 99%

Dental treatment of a patient with Opitz G/BBB syndrome

Giovani¹,

Marinho

Andia-Merlin³

2016

Special Care in Dentistry

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Opitz G/BBB syndrome is a genetic condition characterized by several abnormalities along the midline of the body, such as hypertelorism, craniofacial deformities, and dysphagia. This study reports the clinical features of Optiz syndrome and its importance in the knowledge of patients who are developmentally challenged as a whole, in order to establish adequate dental treatment for a certain clinical case. A 19-year-old patient visited the Paulista University for a dental treatment. The extraoral examination revealed ocular hypertelorism (wide-spaced eyes), oblique eyelids, epicanthus, low-set cart, and intellectual disability. During the intraoral examination, large caries lesions were observed surrounding the braces of the fixed orthodontic appliance and poor oral hygiene. Preventive and restorative treatments were carried out. It was concluded that the knowledge of patients with special needs as a whole is mandatory for an adequate dental treatment. This is a case report that highlights the importance of dentist and interdisciplinary care attendance for all patient systems, the examination and analyses should not be restricted to the oral cavity.

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A MID1 gene mutation in a patient with Opitz G/BBB syndrome that altered the 3D structure of SPRY domain

Cited by 15 publications

References 29 publications

MID1 Catalyzes the Ubiquitination of Protein Phosphatase 2A and Mutations within Its Bbox1 Domain Disrupt Polyubiquitination of Alpha4 but Not of PP2Ac

MID1 Catalyzes the Ubiquitination of Protein Phosphatase 2A and Mutations within Its Bbox1 Domain Disrupt Polyubiquitination of Alpha4 but Not of PP2Ac

Two Novel Pathogenic MID1 Variants and Genotype-Phenotype Correlation Reanalysis in X-Linked Opitz G/BBB Syndrome

Dental treatment of a patient with Opitz G/BBB syndrome

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