G syndrome (hypertelorism with esophageal abnormality and hypospadias, or hypospadias‐dysphagia, or “Opitz‐Frias” or “opitz‐G” syndrome)—perspective in 1987 and bibliography

Opitz, John M.; Reynolds, James F.

doi:10.1002/ajmg.1320280203

Cited by 86 publications

(69 citation statements)

References 19 publications

(6 reference statements)

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“…Opitz G/BBB syndrome (OS) is a multiple congenital anomaly disorder affecting primarily midline structures (MIM]s 145410, 300000) [Opitz, 1987;Opitz et al, 1969aOpitz et al, , 1969b. OS patients usually present with characteristic facial anomalies, including hypertelorism/telecanthus and clefts of lip and/or palate (CL/P), laryngo-tracheo-esophageal (LTE) abnormalities, congenital heart and anal defects, and hypospadias [Cox et al, 2000;De Falco et al, 2003;Ferrentino et al, 2007;Gaudenz et al, 1998;Mnayer et al, 2006;Pinson et al, 2004;Robin et al, 1996;So et al, 2005;Winter et al, 2003].…”

Section: Introductionmentioning

confidence: 99%

MID1 mutations in patients with X-linked Opitz G/BBB syndrome

2008

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Communicated by Arnold MunnichMutations in the MID1 gene are responsible for the X-linked form of Opitz G/BBB syndrome (OS), a disorder that affects the development of midline structures. OS is characterized by hypertelorism, hypospadias, laryngotracheo-esophageal (LTE) abnormalities, and additional midline defects. Cardiac, anal, and neurological defects are also present. The expressivity of OS is highly variable, even within the same family. We reviewed all the MID1 mutations reported so far, in both familial and sporadic cases. The mutations are scattered along the entire length of the gene and consist of missense and nonsense mutations, insertions and deletions, either inframe or causing frameshifts, and deletions of either single exons or the entire MID1 coding region. The variety of described mutations and the lack of a strict genotype-phenotype correlation confirm the previous suggestion of the OS phenotype being caused by a loss-of-function mechanism. However, although a specific mutation cannot entirely account for the observed phenotype, we observed preferential association between some types of mutation and specific clinical manifestations, e.g., brain anatomical defects and truncating mutations. This may suggest that the pathogenetic mechanism underlying the OS phenotype is more complex and may vary among the affected organs. Hum Mutat 29(5), [584][585][586][587][588][589][590][591][592][593][594] 2008.

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Section: Introductionmentioning

confidence: 99%

MID1 mutations in patients with X-linked Opitz G/BBB syndrome

2008

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“…As hypospadias forms part of OS, 8 we hypothesized that the gene responsible for the X-linked form of OS, the MID1 gene, might be involved in the development of hypospadias as a mild form of OS. 9,10 We identified one nonsense mutation, one missense mutation and two synonymous variants.…”

Section: Discussionmentioning

confidence: 99%

“…Mutations in the MID1 gene cause the X-linked form of Opitz G/BBB syndrome (OS, characterized by midline abnormalities such as hypertelorism, cleft lip/palate, tracheo-esophageal abnormalities, cardiac defects and hypospadias). [8][9][10] The function of MID1 is highly conserved in vertebrates, and experiments conducted in mice and chicken showed that MID1 expression correlated well with the tissues affected in OS. 11,12 In situ hybridization studies on human embryos showed that the expression of MID1 was localized in undifferentiated cells of midline structures including the urogenital system.…”

Section: Introductionmentioning

confidence: 99%

Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome

et al. 2011

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Hypospadias is a common congenital malformation in boys in which the urethral meatus opens on the underside of the penis. It is considered a complex disorder with several genes involved and the molecular etiology is just beginning to be revealed. As more than 85% of Opitz G/BBB syndrome (OS) patients with MID1 mutations are manifested with hypospadias, we have investigated the association between the MID1 gene and hypospadias. DNA from 114 hypospadias cases was analyzed with direct sequencing of the MID1 gene. Genotyping analysis was performed for the single-nucleotide polymorphism (SNP) c.1230G4A in 370 individuals with varying degrees of hypospadias and compared with 759 healthy controls. We identified one nonsense mutation c.712G4T (p.E238X), one missense mutation c.1679A4G (p.K560R) and two synonymous variants c.1230G4A (p.S410S) and c.1284T4G (p.V428V). We also detected a significant difference in the rare allele frequency of SNP c.1230G4A in hypospadias patients as compared with controls (P¼0.016). Our finding suggests that hypospadias associated with hypertelorism is the mildest phenotype in OS caused by MID1 mutations.

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“…Opitz G/BBB syndrome (OS) is a congenital anomaly disorder characterized by developmental defects of midline structures (Opitz, 1987). OS patients present with hypertelorism, hypospadias, and laryngo-tracheo-esophageal (LTE) anomalies.…”

Section: Introductionmentioning

confidence: 99%

Lack ofMid1, the Mouse Ortholog of the Opitz Syndrome Gene, Causes Abnormal Development of the Anterior Cerebellar Vermis

Lancioni

Pizzo²,

Fontanella³

et al. 2010

J. Neurosci.

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Opitz G/BBB syndrome (OS) is a genetic disorder characterized by midline developmental defects. Male patients with the X-linked form of OS, caused by loss-of-function mutations in the MID1 gene, show high variability of the clinical signs. MID1 encodes a ubiquitin ligase that controls phosphatase 2A, but its role in the pathogenesis of the disease is still unclear. Here, we report a mouse line carrying a nonfunctional ortholog of the human MID1 gene, Mid1. Mid1-null mice show the brain anatomical defect observed in patients (i.e., hypoplasia of the anterior portion of the medial cerebellum, the vermis). We found that the presence of this defect correlates with motor coordination and procedural and nonassociative learning impairments. The defect is limited to the most anterior lobes of the vermis, the region of the developing cerebellum adjacent to the dorsal midbrain. Analyses at midgestation reveal that lack of Mid1 causes the shortening of the posterior dorsal midbrain, the rostralization of the midbrain/cerebellum boundary, and the downregulation of a key player in the development of this region, Fgf17. Thus, lack of Mid1 causes a misspecification of the midbrain/cerebellar boundary that results in an abnormal development of the most anterior cerebellar lobes. This animal model provides a tool for additional in vivo studies of the physiological and pathological role of the Mid1 gene and a system to investigate the development and function of anterior cerebellar domains.

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G syndrome (hypertelorism with esophageal abnormality and hypospadias, or hypospadias‐dysphagia, or “Opitz‐Frias” or “opitz‐G” syndrome)—perspective in 1987 and bibliography

Cited by 86 publications

References 19 publications

MID1 mutations in patients with X-linked Opitz G/BBB syndrome

MID1 mutations in patients with X-linked Opitz G/BBB syndrome

Hypospadias associated with hypertelorism, the mildest phenotype of Opitz syndrome

Lack ofMid1, the Mouse Ortholog of the Opitz Syndrome Gene, Causes Abnormal Development of the Anterior Cerebellar Vermis

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