A MID1 mutation associated with reduced penetrance of X-linked Opitz G/BBB syndrome

Abstract

The X-linked Opitz G/BBB syndrome (OS) is a congenital malformation disorder characterized by hypertelorism, swallowing difficulties, hypospadias, and additional midline malformations. Loss of function mutations in the MID1 gene at Xp22.3 are responsible for the X-linked form of OS. Various mutations are found all over the gene but without a clear genotype-phenotype correlation. We describe additional family studies of a previously reported boy with a relatively mild form of OS, caused by the unique p.Lys370Glu (c.1108A>G) mutation in MID1. The same mutation was found in his clinically affected brother but also in the healthy maternal uncle. To our knowledge, this is the first report of a MID1 missense mutation causing non-penetrance in a male.

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

“…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).…”

“…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).…”

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

“…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].…”

Dental treatment of a patient with Opitz G/BBB syndrome

“…Its exact way of genetic transmission is still unknown, although it can be related to the autosomal dominant inheritance or X‐linked syndrome. There are two forms of Opitz syndrome, which are distinguished by their genetic causes and patterns of inheritance: X‐linked Opitz syndrome, which is caused by mutation in a specific gene MiD1 (midline 1) on chromosome X, and autosomal dominant form, which is caused by mutation in the still unidentified gene on chromosome 22 caused by deletion of a small piece of chromosome 22, specifically 22q11.2, because of this researchers consider this condition as part of the 22q11.2 deletion syndrome . Signs and symptoms of the syndrome include congenital heart disease (74% of subjects), palatal abnormalities (69%), velopharyngeal incompetence, submucous cleft palate, facial features (predominantly in Caucasians), and learning disabilities (70–90%) .…”