Opitz GBBB syndrome: Chromosomal evidence of an X‐linked form

Abstract

BBB syndrome and G syndrome were originally reported as distinct X-linked disorders. Clinical studies indicated that BBB and G syndromes were likely to represent variant expression of the same disorder, now referred to as "Opitz" GBBB syndrome. Several occurrences of male-to-male transmission in both syndromes led to the hypothesis that GBBB syndrome was a single autosomal dominant, sex influenced disorder, now tentatively mapped to 5p12-13. We report on a large pedigree in which GBBB syndrome appears to cosegregate with a pericentric inversion of the X chromosome inv(X)(p22.3q26). It indicates the possible existence of a true X-linked form of GBBB syndrome, which does not appear phenotypically different from its autosomal counterpart. The gene could map in the vicinity of the breakpoints, in Xp or Xq. The existence of two genes affecting a common pathogenetic pathway could explain the gender-dependent expressivity of GBBB phenotype.

Characterization and Physical Mapping in Human and Mouse of a Novel RING Finger Gene in Xp22

“…All the mutations described in these patients disrupt the C-terminal domain of the gene, suggesting that most likely the formation of truncated transcripts disrupting the C-terminal domain is the main underlying mechanism for this disorder. However, the existence of a family with classic Opitz G syndrome cosegregating with a pericentric inversion of the X-chromosome inv(X)(p22.3q26) that abolishes expression of MID1 (Verloes et al, 1995 andQuaderi et al, 1997) suggests that no other disorders are associated with complete loss of function. Therefore, the only means by which MLS, Aicardi syndrome, or Goltz syndrome could be caused by alterations in this gene would be through developmental-and/or tissue-specific alteration of expression.…”

The MID1/PP2A complex: a key to the pathogenesis of Opitz BBB/G syndrome

“…Starting from the Xp breakpoint of a pericentric inversion of chromosome X, which was found to associate with OS in a twenty-member family, (36) the gene for the X-linked form of OS was identified. (37) The MID1 gene covers a genomic region of about 300 kb and consists of nine coding exons and multiple non-coding exons.…”

“…(36,40) This makes genotype-phenotype correlations and predictive genetic counseling extremely difficult. The molecular mechanisms of this variability remain to be investigated.…”

Further delineation of the Opitz G/BBB syndrome: Report of an infant with complex congenital heart disease and bladder exstrophy, and review of the literature

“…Rectourethral fistula Stevens and Wilroy [1988] 2 patients Bifid, medially displaced ureters 1 patient Duplication of the calyceal system 1 patient Duplication of the ureter with reflux Stoll et al [1985] Case 1 + + Cleft glans, hypoplastic scrotum, unpalpable left testis Urioste et al [1995] Case 1 + Cleft scrotum with anterior displacement, ureteral reflux with anomalous vesical implantation of the ureter Van Biervliet et al [1975] Case 2 + Verloes et al [1989] Case 2 + Rectourethral fistula Case 3 + Bifid scrotum with ectopic but palpable testes Verloes et al [1995] Case II-6 Rectoperineal fistula, imperforate hymen Case II-8…”