Nosology of omodysplasia

Borochowitz, Zvi; Barak, Moshe; Hershkowitz, S.

doi:10.1002/ajmg.1320580416

Cited by 10 publications

(7 citation statements)

References 8 publications

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“…The description of similarly affected individuals born to phenotypically normal, consanguineous parents supported the suggestion that omodysplasia can have autosomal recessive inheritance and micromelia [Borochowitz et al, 1991;Kiss et al, 1991;Baxova et al, 1994;Al Gazali and Al-Asaad, 1995;Stoll et al, 1995;Masel et al, 1998]. Thus there are two forms of omodysplasia, one characterized by normal stature and dominant inheritance and the other by recessive inheritance and micromelia [Borochowitz et al, 1995;Maroteaux, 1995].…”

Section: Introductionmentioning

confidence: 53%

Omodysplasia: An affected mother and son

et al. 2002

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We describe a second family with mother to son transmission of omodysplasia, a rare skeletal dysplasia characterized by shortened humeri, shortened first metacarpals and craniofacial dysmorphism. The mother in this family had been diagnosed previously with Robinow syndrome; subsequently, her diagnosis was reclassified. Her pregnancy was closely monitored antenatally with serial ultrasound examinations. Delayed ossification of the humerus was noted prenatally. Her son had ambiguous genitalia and similar skeletal manifestations as his mother. A comparison to other known and suspected cases of dominant omodysplasia is presented. Our observations confirm the existence of a dominant variant of omodysplasia, document genital hypoplasia as an important feature of this syndrome in males and highlight the need to differentiate this entity from Robinow syndrome.

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Section: Introductionmentioning

confidence: 53%

Omodysplasia: An affected mother and son

et al. 2002

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“…Based on the similarities to Patients 4 and 5 reported by Maroteaux et al [1989], Borochowitz et al [1991] proposed that these patients had a distinct skeletal dysplasia syndrome they called “familial congenital micromelic dysplasia with dislocation of the radius and distinct face.” The description of similarly affected individuals born to phenotypically normal, consanguineous parents supported the suggestion that omodysplasia can have autosomal recessive inheritance and micromelia [Borochowitz et al, 1991; Kiss et al, 1991; Baxova et al, 1994; Al Gazali and Al‐Asaad, 1995; Stoll et al, 1995; Masel et al, 1998]. Thus there are two forms of omodysplasia, one characterized by normal stature and dominant inheritance and the other by recessive inheritance and micromelia [Borochowitz et al, 1995; Maroteaux, 1995].…”

Section: Introductionmentioning

confidence: 95%

Tyrosine hydroxylase mRNA and protein are down‐regulated by chronic clozapine in both the mesocorticolimbic and the nigrostriatal systems

Biguet

Dumas

Mallet

2003

J of Neuroscience Research

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The dopaminergic system is one of the most important targets for pharmacological treatment of schizophrenia. Despite substantial work on mechanisms of action, it is not clear which dopaminergic pathways mediate the therapeutic effects of antipsychotic drugs. It has been shown that chronic clozapine, an atypical antipsychotic, decreases dopamine levels in the mesocorticolimbic system but not in the nigrostriatal system. Because tyrosine hydroxylase is the rate-limiting enzyme in the biosynthesis of dopamine, we studied the effect of chronic clozapine in both dopaminergic systems. We demonstrated a decrease of tyrosine hydroxylase mRNA not only in the ventral tegmental area but also in the substantia nigra, the cell body areas of the mesocorticolimbic and the nigrostriatal systems, respectively. The reduced tyrosine hydroxylase mRNA level in these areas is accompanied by an ample reduction in the tyrosine hydroxylase protein level in their corresponding axonal terminal fields, the nucleus accumbens and the striatum. There was thus discordance between the clozapine-induced decrease of tyrosine hydroxylase mRNA and protein and the absence of an effect on dopamine levels in the nigrostriatal system. It has been suggested that reduced levels of dopamine in the mesocorticolimbic system are required for the antipsychotic effect of the drug. Therefore, the modulation of tyrosine hydroxylase gene expression by clozapine in the mesocorticolimbic system might be necessary for its antipsychotic effect; this effect might be of relevance when considering new atypical agents.

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“…The only reported phenotype associated with this gene is autosomal recessive omodysplasia‐1 (OMIM #258315), which is caused by truncating variants or partial/full gene deletions in GPC6 (Campos‐Xavier et al, 2009). First described in the 1990s, the autosomal recessive form of omodysplasia‐1 is rare with approximately 25 reported cases in the literature (Bayat et al, 2020; Borochowitz et al, 1995). Phenotypically, patients with omodysplasia‐1 have severe short stature (standard deviation range: −3 to −5) with shortening and distal tapering of the proximal long bones of the upper and lower extremities, creating a club‐like appearance.…”

Section: Introductionmentioning

confidence: 99%

Five siblings expand the spectrum of GPC6‐related skeletal dysplasia

Crenshaw

Meyers

Brown

et al. 2023

American J of Med Genetics Pt A

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Skeletal dysplasias broadly include disorders of cartilage or bone. Omodysplasia‐1 is a type of skeletal dysplasia caused by biallelic loss of function variants in the GPC6 gene. GPC6 codes for the protein glypican 6 (GPC6) (OMIM *604404), which stimulates bone growth. We report a family in which five out of nine children were presented with a skeletal dysplasia characterized phenotypically by mild short stature and rhizomelia. All affected individuals were found to have homozygous missense variants in GPC6: c.511 C>T (p.Arg171Trp). Radiograph findings included rhizomelic foreshortening of all four extremities, coxa breva, and ulna minus deformity. Using a Hedgehog (Hh) reporter assay, we demonstrate that the variant found in this family results in significantly reduced stimulation of Hh activity when compared to the wild‐type GPC6 protein, however protein function is still present. Thus, the milder phenotype seen in the family presented is hypothesized due to decreased GPC6 protein activity versus complete loss of function as seen in omodysplasia‐1. Given the unique phenotype and molecular mechanism, we propose that this family's findings widen the phenotypic spectrum of GPC6‐related skeletal dysplasias.

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Nosology of omodysplasia

Cited by 10 publications

References 8 publications

Omodysplasia: An affected mother and son

Omodysplasia: An affected mother and son

Tyrosine hydroxylase mRNA and protein are down‐regulated by chronic clozapine in both the mesocorticolimbic and the nigrostriatal systems

Five siblings expand the spectrum of GPC6‐related skeletal dysplasia

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