Bernard-Soulier syndrome associated with 22q11.2 microdeletion

Nakagawa, Masao; Okuno, Masahiko; Okamoto, Nobuhiko; Fujino, Hidetoshi; Katô, Hirofumi

doi:10.1002/1096-8628(2001)9999:9999<::aid-ajmg1176>3.0.co;2-t

Cited by 29 publications

(13 citation statements)

References 11 publications

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“…The first is the bleeding disorder Bernard‐Soulier syndrome, which is caused by homozygous or compound heterozygous mutations of the GP1BB gene encoding the platelet glycoprotein GPIb/IX receptor. At least four patients have been reported in which the common 22q11.2 deletion served as one of the two mutations [Budarf et al, ; Ludlow et al, ; Lascone et al, ; Nakagawa et al, ].…”

Section: Discussionmentioning

confidence: 99%

Deletion 16p13.11 uncovers NDE1 mutations on the non‐deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption

Paciorkowski

Keppler‐Noreuil

Robinson

et al. 2013

American J of Med Genetics Pt A

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Deletions of 16p13.11 have been associated with a variety of phenotypes, and have also been found in normal individuals. We report on two unrelated patients with severe microcephaly, agenesis of the corpus callosum, scalp rugae, and a fetal brain disruption (FBD)-like phenotype with inherited deletions of 16p13.11. The first patient was subsequently found on whole exome sequencing to have a nonsense mutation (p.R44X) in NDE1 on the non-deleted chromosome 16 homolog. We then undertook copy number studies of 16p13.11 and sequencing of NDE1 in nine additional patients with a similar severe microcephaly, agenesis of the corpus callosum, and FBD-like phenotype. The second patient was found to have an inherited deletion of the entire NDE1 gene combined with a frameshift mutation (c.1020-1021het_delGA) in the non-deleted NDE1. These observations broaden the phenotype seen in NDE1-related microcephaly to include FBD. These data also represent the second described syndrome, after Bernard-Soulier syndrome, where an autosomal recessive condition combines an inherited segmental duplication mediated deletion with a mutation in a gene within the non-deleted homolog. Finally, we performed informatics analysis of the 16p13.11 gene content, and found that there are many genes within the region with evidence for role(s) in brain development. Sequencing of other candidate genes in this region in patients with deletion 16p13.11 and more severe neurophenotypes may be warranted.

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Section: Discussionmentioning

confidence: 99%

Deletion 16p13.11 uncovers NDE1 mutations on the non‐deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption

Paciorkowski

Keppler‐Noreuil

Robinson

et al. 2013

American J of Med Genetics Pt A

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“…In these, there is the combination of haploinsufficiency of the GPIb gene in the deficient chromosome 22 due to a microdeletion and an allelic mutation of the intact chromosome 22. (10,11) …”

Section: Discussionmentioning

confidence: 99%

Hematological abnormalities and 22q11.2 deletion syndrome

Rosa¹,

Rosa²,

Santos³

et al. 2011

Rev. Bras. Hematol. Hemoter.

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The 22q11.2 deletion syndrome (22q11DS) is a common genetic disease characterized by broad phenotypic variability. Despite the small number of studies describing hematological alterations in individuals with 22q11DS, it appears that these abnormalities are more frequent than previously imagined. Thus, the objective of our study was to report on a patient with 22q11DS presenting thrombocytopenia and large platelets and to review the literature. The patient, a 13-year-old boy, was originally evaluated due to craniofacial dysmorphia and speech delay. He also had a history of behavioral changes, neuropsychomotor delay and recurrent otitis/sinusitis. The identification of a 22q11.2 microdeletion by fluorescent in situ hybridization diagnosed the syndrome. Despite his hematological alterations, he only had a history of epistaxis and bruising of the upper and lower limbs. Assessments of the prothrombin time, thrombin time, partial thromboplastin time, bleeding time, fibrinogen levels and platelet aggregation (including the ristocetin induced platelet aggregation test) were all normal. Hematological alterations observed in 22q11DS are directly related to the genetic disorder itself (especially in respect to deletion of the GPIb gene) and secondary to some clinical findings, such as immunodeficiency. Macrothrombocytopenia is increasingly being considered a feature of the broad spectrum of 22q11DS and may potentially be a clinical marker for the syndrome.

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“…The 22q11 deletion syndromes may be associated with a severe Bernard–Soulier syndrome phenotype if the single remaining GPIBB gene contains an independently inherited mutation (Budarf et al , 1995). Children with 22q11 deletions may require major cardiac surgery in infancy and therefore may have a significant bleeding risk (Lascone et al , 2001; Nakagawa et al , 2001)…”

Section: Bernard–soulier Syndrome (Thrombocytopenia With Large Platelmentioning

confidence: 99%

A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO

et al. 2006

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SummaryThe inherited platelet disorders are an uncommon cause of symptomatic bleeding. They may be difficult to diagnose (and are likely to be under-diagnosed) and pose problems in management. This review discusses the inherited platelet disorders summarising the current state of the art with respect to investigation and diagnosis and suggests how to manage bleeding manifestations with particular attention to surgical interventions and the management of pregnancy.

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Bernard-Soulier syndrome associated with 22q11.2 microdeletion

Cited by 29 publications

References 11 publications

Deletion 16p13.11 uncovers NDE1 mutations on the non‐deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption

Deletion 16p13.11 uncovers NDE1 mutations on the non‐deleted homolog and extends the spectrum of severe microcephaly to include fetal brain disruption

Hematological abnormalities and 22q11.2 deletion syndrome

A review of inherited platelet disorders with guidelines for their management on behalf of the UKHCDO

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