Urofacial (ochoa) syndrome: A literature review

Osorio, Sebastian; Rivillas, Néstor David; Martı́nez, Jorge

doi:10.1016/j.jpurol.2021.01.017

Cited by 12 publications

(16 citation statements)

References 64 publications

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“…Inf.) 68,174,175 . This indicates that both SULF2 and HPSE2 are required for normal homeostasis and basal response to stimuli.…”

Section: Resultsmentioning

confidence: 99%

“…This indicates that both SULF2 and HPSE2 are required for normal homeostasis and basal response to stimuli. The involvement of HPSE2 in response to stimuli was confirmed in the homozygous Hpse2 gene trap mouse, which developed normally but showed deficient responses to chemical and electrical field stimulation and showed low weight gain after weaning and died early in life 174,175 . In the other side, both Sulf1 -/and hpse -/mice develop and live normally, are anatomically normal fertile, and show non overt phenotypes 14,186 (included in Group III).…”

Section: Hs Chain Remodeling and Biosynthesis Arrestmentioning

confidence: 87%

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Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

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Proteoglycans are complex macromolecules formed of glycosaminoglycan chains covalently linked to core proteins through a linker tetrasaccharide common to heparan sulfate proteoglycans (HSPG) and chondroitin sulfate proteoglycans (CSPG). Biosynthesis of a single proteoglycan requires the expression of dozens of genes, which together create the large structural and functional diversity reflected by the numerous diseases or syndromes associated to their genetic variability. Among proteoglycans, HSPG are the most structurally and functionally complex. To decrease this complexity, we retrieved and linked information on pathogenic variants, polymorphism, expression, and literature databases for 50 genes involved in the biosynthesis of HSPG core proteins, heparan sulfate (HS) chains, and their linker tetrasaccharide. This resulted in a new gene organization and biosynthetic pathway representation in which the phenotypic continuum of disorders as linkeropathies and other pathologies could be predictable. Moreover, ubiquitous NDST1, GLCE, HS2ST1, and HS6ST1 appeared to generate ubiquitous heparan sulfate (HS) sequences essential for normal development and homeostasis, whereas the tissue restricted NDST2-4, HS6ST2-3, and HS3ST1-6 appeared to generate specialized HS sequences mainly involved in responsiveness to stimuli. Supported by data on genetic polymorphism and clinical variants, we afford a new vision of HSPG involvement in homeostasis, disease, vulnerability to disease, and behavioral disorders.

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“…Inf.) 68,174,175 . This indicates that both SULF2 and HPSE2 are required for normal homeostasis and basal response to stimuli.…”

Section: Resultsmentioning

confidence: 99%

Section: Hs Chain Remodeling and Biosynthesis Arrestmentioning

confidence: 87%

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Ouidja

Biard

Chantepie

et al. 2022

Preprint

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“…Urofacial (Ochoa) syndrome (UFS) is rare autosomal recessive disease featuring urinary voiding dysfunction and a grimace upon smiling ( Elejalde, 1979 ; Ochoa 2004 ; Newman and Woolf, 2018 ; Osorio et al, 2021 ). The urinary tract phenotype is characterized by bladder dyssynergia, with the detrusor contracting against and incompletely dilated outflow tract.…”

Section: Introductionmentioning

confidence: 99%

Expanding the HPSE2 Genotypic Spectrum in Urofacial Syndrome, A Disease Featuring a Peripheral Neuropathy of the Urinary Bladder

et al. 2022

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Urofacial (also called Ochoa) syndrome (UFS) is an autosomal recessive congenital disorder of the urinary bladder featuring voiding dysfunction and a grimace upon smiling. Biallelic variants in HPSE2, coding for the secreted protein heparanase-2, are described in around half of families genetically studied. Hpse2 mutant mice have aberrant bladder nerves. We sought to expand the genotypic spectrum of UFS and make insights into its pathobiology. Sanger sequencing, next generation sequencing and microarray analysis were performed in four previously unreported families with urinary tract disease and grimacing. In one, the proband had kidney failure and was homozygous for the previously described pathogenic variant c.429T>A, p.(Tyr143*). Three other families each carried a different novel HPSE2 variant. One had homozygous triplication of exons 8 and 9; another had homozygous deletion of exon 4; and another carried a novel c.419C>G variant encoding the missense p.Pro140Arg in trans with c.1099-1G>A, a previously reported pathogenic splice variant. Expressing the missense heparanase-2 variant in vitro showed that it was secreted as normal, suggesting that 140Arg has aberrant functionality after secretion. Bladder autonomic neurons emanate from pelvic ganglia where resident neural cell bodies derive from migrating neural crest cells. We demonstrated that, in normal human embryos, neuronal precursors near the developing hindgut and lower urinary tract were positive for both heparanase-2 and leucine rich repeats and immunoglobulin like domains 2 (LRIG2). Indeed, biallelic variants of LRIG2 have been implicated in rare UFS families. The study expands the genotypic spectrum in HPSE2 in UFS and supports a developmental neuronal pathobiology.

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“…Urofacial, or Ochoa, syndrome (UFS), is an autosomal recessive condition causing lifelong ill health with potentially fatal complications (Ochoa 2004;Osorio et al, 2021). Affected females and males have dyssynergic bladders in which the detrusor smooth muscle (DSM) in the bladder body contracts against an outflow tract that fails to dilate fully.…”

Section: Introductionmentioning

confidence: 99%

Neurogenic defects underlie functional bladder outflow tract obstruction associated with biallelic variants inLRIG2

Grenier

Lopes

Cueto‐González

et al. 2022

Preprint

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Urinary tract malformations account for half of all children with kidney failure, and some have defined monogenic causes. One such disorder is urofacial, or Ochoa, syndrome (UFS), an autosomal recessive disease featuring a dyssynergic bladder with detrusor smooth muscle contracting against an undilated outflow tract. Incomplete voiding predisposes to urosepsis and kidney failure. Half of individuals with UFS carry biallelic variants in HPSE2, whereas some carry variants in LRIG2 (leucine rich repeats and immunoglobulin like domains 2). We report one new kindred where the index case presented with fetal hydronephrosis and postnatally had urosepsis and functional bladder outlet obstruction. He had the grimace that, together with urinary tract disease, characterizes UFS. While HPSE2 sequencing was normal, he carried a homozygous, predicted pathogenic, stop variant (c.1939C>T; p.Arg647*) in LRIG2. Hypothesizing that neurogenic defects underlie LRIG2-associated bladder dysfunction, we studied Lrig2 homozygous mutant mice. Juveniles had enlarged bladders and ex vivo physiology experiments showed neurogenic defects in outflow tract relaxation. Mutants also displayed abnormal detrusor contractility. Moreover, there were nuanced differences in physiological defects between the sexes. The current case emphasizes that urinary tract disease in UFS begins before birth. Putting this family in the context of all reported urinary tract disease-associated LRIG2 variants, the urinary and facial phenotype of UFS occurs with biallelic putative loss of function variants, but missense variants lead to bladder-limited disease without the grimace. Finally, our murine observations support the hypothesis that UFS is a genetic autonomic neuropathy of the bladder affecting outflow tract and bladder body function.

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Urofacial (ochoa) syndrome: A literature review

Cited by 12 publications

References 64 publications

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Variability in proteoglycan biosynthetic genes reveals new facets of heparan sulfates diversity. A systematic review and analysis

Expanding the HPSE2 Genotypic Spectrum in Urofacial Syndrome, A Disease Featuring a Peripheral Neuropathy of the Urinary Bladder

Neurogenic defects underlie functional bladder outflow tract obstruction associated with biallelic variants inLRIG2

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