RGD Reference Report - Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant.

General

Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant.
Authors:	Vettore, S Scandellari, R Moro, S Lombardi, AM Scapin, M Randi, ML Fabris, F
Citation:	Vettore S, etal., Haematologica. 2008 Nov;93(11):1743-7. doi: 10.3324/haematol.12830. Epub 2008 Sep 24.
RGD ID:	10450842
Pubmed:	PMID:18815197 (View Abstract at PubMed)
DOI:	DOI:10.3324/haematol.12830 (Journal Full-text)
In Italy, a significant proportion of patients with autosomal dominant inheritance of macrothrombocytopenia have been recognized as having heterozygous Bernard-Soulier syndrome carrying the Bolzano-type defect. This condition prompted a systematic review of our out-patients with chronic isolated macrothrombocytopenia. We recognized that the affected members of two unrelated families represented a new variant of heterozygous Bernard-Soulier Syndrome with autosomal dominant inheritance. Sequencing analysis of the GPIbalpha gene revealed a novel heterozygous mutation, A169C, resulting in an N41H substitution in the protein. This aminoacid belongs to the first leucine-rich repeat of the chain. The molecular modeling suggests that the replacement of the N41 with a histidine (N41H) drastically disturbs the structure of the first portion of GPIbalpha N-terminal, directly involved in von Willebrand factor binding. As a consequence, platelet aggregation to 1.2 mg/mL of ristocetin is slightly impaired and flow cytometry reveals a reduced binding of monoclonals directed against N-terminal epitopes of the GPIbalpha.

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Term	Qualifier	Evidence	With	Reference	Notes	Source	Original Reference(s)
Bernard-Soulier Syndrome, Autosomal Dominant		IAGP		10450842	DNA:missense mutation: :p.N41H (169A>C) (human)	RGD
Bernard-Soulier Syndrome, Autosomal Dominant		ISO	GP1BA (Homo sapiens)	10450842; 10450842	DNA:missense mutation: :p.N41H (169A>C) (human)	RGD

Objects Annotated

Genes (Rattus norvegicus)

Gp1ba (glycoprotein Ib platelet subunit alpha)

Genes (Mus musculus)

Gp1ba (glycoprotein 1b, alpha polypeptide)

Genes (Homo sapiens)

GP1BA (glycoprotein Ib platelet subunit alpha)

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Novel point mutation in a leucine-rich repeat of the GPIbalpha chain of the platelet von Willebrand factor receptor, GPIb/IX/V, resulting in an inherited dominant form of Bernard-Soulier syndrome affecting two unrelated families: the N41H variant.