Johanson–Blizzard syndrome: Report of a novel mutation and severe liver involvement

Al‐Dosari, Mohammed S.; Al‐Muhsen, Saleh; Al‐Jazaeri, Ayman; Mayerle, Julia; Zenker, Martin; Alkuraya, Fowzan S.

doi:10.1002/ajmg.a.32401

Cited by 18 publications

(20 citation statements)

References 17 publications

(23 reference statements)

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“…The male twin presented typical clinical features of JBS (listed in order of prevalence in patients with JBS): pancreatic insufficiency (98%), nasal alae hypoplasia (98%), dental hypoplasia/agenesis (96%), short stature (84%), scalp defects (72%), deafness (69%), and mental retardation (69%) (Al-Dosari et al, 2008;Alkhouri et al, 2008;Elting et al, 2008;Almashraki et al, 2011;Fallahi et al, 2011;Hwang et al, 2011).…”

Section: Discussionmentioning

confidence: 99%

Case Report Johanson-Blizzard syndrome: a report of gender-discordant twins with a novel UBR1 mutation

et al. 2014

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ABSTRACT. Johanson-Blizzard syndrome (JBS) is a rare autosomal recessive disorder resulting from loss-of-function mutations in the UBR1 gene. JBS can be easily recognized by its unique clinical presentation (including exocrine pancreatic insufficiency, hypoplasia/ aplasia of the alae nasi, congenital scalp defects, sensorineural hearing loss, growth retardation, psychomotor retardation, and anal and genitourinary anomalies). The objective of this study is to report on the first familial case of gender-discordant twins presenting JBS and a novel mutation in the UBR1 gene. We also review literature describing molecularly confirmed cases of JBS. The female twin developed refractory severe diarrhea after the second month of life and died at the age of 3 months. The male twin also developed diarrhea and failure to thrive after the 3 month of life but improved when nutrition support and pancreatic enzyme replacement was started, and he has survived into adolescence. Both patients presented typical clinical features of JBS. A homozygous nonsense mutation (c.3682C>T; p.Q1228X) in UBR1 was confirmed. Severe presentation of JBS usually involves deleterious (nonsense, frameshift, or splice-site) mutations in the UBR1 gene that are thought to completely abolish the expression of a functional protein product, as in this familial case; however, milder presentation of JBS has occasionally been observed with missense mutations in at least 1 of the 2 copies of UBR1, in which there may be residual activity of the product of this gene. Early diagnosis and adequate treatment are crucial for a favorable outcome.

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Section: Discussionmentioning

confidence: 99%

Case Report Johanson-Blizzard syndrome: a report of gender-discordant twins with a novel UBR1 mutation

et al. 2014

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“…Several nonsense, splice site and frameshift mutations, as well as some missense changes of the UBR1 gene have been described [1,2,8,9,33] since the discovery of this gene defect in JBS. Mutations that lead to premature stop codons are the most prevalent ones.…”

Section: Pathogenesismentioning

confidence: 98%

“…The following anomalies have anecdotally been reported to be associated with JBS: congenital cataracts, sacral hiatus, and neonatal cholestasis [1,7,18]. …”

Section: Clinical Featuresmentioning

confidence: 99%

“…Some patients with JBS suffer from genital malformations (undescended testes, small penis, hypospadias in male infant and duplex of vagina in female infants), ureteral abnormalities (e.g., vesicoureteral reflux, duplex of the uterus), anorectal anomalies (e.g., imperforate anus, rectoureteral and recto-vaginal fistula), and congenital heart defects (e.g., dextrocardia, dilated cardiomyopathy, atrial and ventricular septal defect) [1,2,7,8,10,14,24]. The following anomalies have anecdotally been reported to be associated with JBS: congenital cataracts, sacral hiatus, and neonatal cholestasis [1,7,18].…”

Section: Clinical Featuresmentioning

confidence: 99%

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et al. 2010

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Johanson-Blizzard syndrome is a very rare autosomal recessive disorder caused by mutations in the Ubiquitin-Protein Ligase E3 Component N-Recognin 1 (UBR1) gene. The syndrome is characterized by exocrine pancreatic insufficiency and a wide range of additional clinical features, including aplasia or hypoplasia of the alae nasi, oligodontia, sensorineural hearing loss, hypothyroidism, scalp defects, mental retardation, and developmental delay. Several other abnormalities in different organs, particularly anorectal, urogenital, and cardiac anomalies have been reported since the first description of this syndrome four decades ago. UBR1 gene defects are underlying the disease. Only symptomatic treatment is available. Exocrine pancreas insufficiency plus abnormal alae nasi is pathognomonic for Johanson-Blizzard syndrome.

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“…Fifty-nine different mutations are known (including published mutations [1][2][3][4][5][6][7][8] and unpublished mutations identified in our lab). These include nonsense mutations (15), splice site mutations (14), small deletions and duplications/insertions causing frameshift (9), small inframe deletions (3) and missense mutations (18).…”

Section: Mutational Spectrummentioning

confidence: 99%