Inherited thrombocytopenias in the era of personalized medicine

Noris, Patrizia; Balduini, Carlo L.

doi:10.3324/haematol.2014.122549

Cited by 11 publications

(17 citation statements)

References 20 publications

(23 reference statements)

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“…And indeed, only when coexpressed with GPIbβ can GPIX be detected on the cell surface, again indicating that GPIbβ interacts with and stabilizes GPIX. From these findings, at least 4 homozygous individuals for the p.P27S mutation, most likely with BSS, are expected in Sardinia, but none has been reported: this may suggest that BSS is likely underdiagnosed in Sardinia, consistent with reports from other studies 38 . Clinicians should thus be aware of the novel p.P27S mutation in the molecular characterization of patients born in Sardinia or of Sardinian origin with a clinical picture of platelet macrocytosis and PLT levels <20-100x10 9 /L, and therefore at high-risk of cerebral hemorrhage.…”

Section: Discussionsupporting

confidence: 86%

A Sardinian founder mutation in GP1BB that impacts thrombocytopenia

Busonero

Steri

Orrù

et al. 2020

Preprint

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To investigate the genetic regulation of platelet (PLT) levels we carried out a whole-genome association analysis in 6,528 Sardinians from the general population of the Lanusei valley. We found 6 variants significantly influencing PLT levels, including a novel rare missense mutation (p.Pro27Ser) in the GP1BB protein that is associated with PLT reduction (P=1.17x10-16). This mutation is rare in the SardiNIA population cohort (frequency of 0.45%), even rarer in the rest of the Sardinian island (frequency of 0.16%), and not reported elsewhere. Notably, GP1BB is involved in Bernard-Soulier syndrome (BSS), a rare autosomal recessive bleeding disorder caused by a defect in the platelet GPIb-IX-V protein complex. Consistently, the 57 identified individuals heterozygous for the p.P27S mutation showed mild thrombocytopenia, morphologically enlarged platelets (P=2.13x10-10), and reduced expression of two GPIb-IX-V-complex components: GPIbα (-26.51%, P=3.66x10-8) and GPIX (-24.69%, P=2.66x10-6). Molecular modeling infers a corresponding reduction in the stability of GP1BB. These observations predict that in homozygosity as well as in individuals carrying specific compound heterozygous configurations, this variant likely causes BSS.

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Section: Discussionsupporting

confidence: 86%

A Sardinian founder mutation in GP1BB that impacts thrombocytopenia

Busonero

Steri

Orrù

et al. 2020

Preprint

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“…MYH9-RD is the most prevalent form of inherited thrombocytopenia worldwide [20] . Patients may present with thrombocytopenia and granulocyte inclusions, with or without nephritis or sensorineural hearing loss.…”

Section: Discussionmentioning

confidence: 99%

Identification of a novel <i>MYH9</i> mutation (p. V782Y) in a Chinese patient with thrombocytopenia: a case report

Tian¹,

Zhang²,

Hu³

et al. 2021

Blood and Genomics

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MYH9-related diseases (MYH9-RD) are a group of autosomal dominant diseases caused by mutations in the MYH9 gene, which are featured by thrombocytopenia, giant platelets and granulocyte cytoplasmic inclusion bodies. MYH9-RD patients generally suffer from bleeding syndromes, progressive kidney disease, deafness, or cataracts. Here, we reported on a case of MYH9-RD. A novel heterozygous mutation of MYH9 (c.2344-2345delGTinsTA, p.T782Y) was discovered by targeted sequencing technology. Immunofluorescence analysis of neutrophils confirmed abnormal aggregation of MYH9 protein. The results of this study should expand the MYH9 gene mutation spectrum and provide reference for subsequent researchers and genetic counseling.

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“…A sporadic MYH9-related disease in a Chinese boy with p.A95T mutation Dear editors, MYH9-related disease (MYH9-RD; MIM#160775) is an autosomal dominant disease characterized by thrombocytopaenia, giant platelets and granulocyte cytoplasmic inclusion bodies. Mutation of the MYH9 gene encoding non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein expressed in all eukaryotes, leads to the abnormal process of platelet formation [1][2][3]. Approximately 35% MYH9-RD patients have sporadic mutations [4].…”

Section: Letter To the Editormentioning

confidence: 99%

“…Generally, MYH9-RD is an inherited macrothrombocytopaenia, which presents with or without a mild bleeding tendency and blue inclusion bodies in granulocytes. Moreover, patients with MYH9-RD present with complications at different ages [1,2]. Some patients only have macrothrombocytopaenia and blue inclusion bodies in granulocytes, without obvious bleeding tendencies or signs of infection [3,10,13].…”

Section: Letter To the Editormentioning

confidence: 99%