Format

Send to

Choose Destination
See comment in PubMed Commons below
Am J Hematol. 2015 Oct;90(10):921-6. doi: 10.1002/ajh.24117.

Novel Gardos channel mutations linked to dehydrated hereditary stomatocytosis (xerocytosis).

Author information

1
Department Of Molecular Medicine And Medical Biotechnologies, "Federico II" University Of Naples, Naples, Italy.
2
Biotecnologie Avanzate, CEINGE, Naples, Italy.
3
Renal Division And Vascular Biology Research Center, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts.
4
Department Of Medicine, Harvard Medical School, Boston, Massachusetts.
5
Medical Genetics Unit, Policlinico Tor Vergata University Hospital, Viale Oxford, Rome, Italy.
6
Department Of Laboratory Medicine, Boston Children's Hospital And Department Of Pathology, Harvard Medical School, Boston, Massachusetts.
7
Dept Of Hospital Laboratories, University Of Massachusetts Medical Center, Worcester, MA.
8
Quest Diagnositics, LLC MA, Marlborough, Massachusetts.

Abstract

Dehydrated hereditary stomatocytosis (DHSt) is an autosomal dominant congenital hemolytic anemia with moderate splenomegaly and often compensated hemolysis. Affected red cells are characterized by a nonspecific cation leak of the red cell membrane, reflected in elevated sodium content, decreased potassium content, elevated MCHC and MCV, and decreased osmotic fragility. The majority of symptomatic DHSt cases reported to date have been associated with gain-of-function mutations in the mechanosensitive cation channel gene, PIEZO1. A recent study has identified two families with DHSt associated with a single mutation in the KCNN4 gene encoding the Gardos channel (KCa3.1), the erythroid Ca(2+) -sensitive K(+) channel of intermediate conductance, also expressed in many other cell types. We present here, in the second report of DHSt associated with KCNN4 mutations, two previously undiagnosed DHSt families. Family NA exhibited the same de novo missense mutation as that recently described, suggesting a hot spot codon for DHSt mutations. Family WO carried a novel, inherited missense mutation in the ion transport domain of the channel. The patients' mild hemolytic anemia did not improve post-splenectomy, but splenectomy led to no serious thromboembolic events. We further characterized the expression of KCNN4 in the mutated patients and during erythroid differentiation of CD34+ cells and K562 cells. We also analyzed KCNN4 expression during mouse embryonic development.

PMID:
26178367
DOI:
10.1002/ajh.24117
[Indexed for MEDLINE]
Free full text
PubMed Commons home

PubMed Commons

0 comments
How to join PubMed Commons

    Supplemental Content

    Full text links

    Icon for Wiley
    Loading ...
    Support Center