scholarly journals Complex Modes of Inheritance in Hereditary Red Blood Cell Disorders: A Case Series Study of 155 Patients

Genes ◽  
2021 ◽  
Vol 12 (7) ◽  
pp. 958
Author(s):  
Immacolata Andolfo ◽  
Stefania Martone ◽  
Barbara Eleni Rosato ◽  
Roberta Marra ◽  
Antonella Gambale ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Diagnostic Yield ◽  
Case Series ◽  
Targeted Next Generation Sequencing ◽  
Complex Modes ◽  
Case Series Study ◽  
Molecular Bases ◽  
Dual Inheritance

Hereditary erythrocytes disorders include a large group of conditions with heterogeneous molecular bases and phenotypes. We analyzed here a case series of 155 consecutive patients with clinical suspicion of hereditary erythrocyte defects referred to the Medical Genetics Unit from 2018 to 2020. All of the cases followed a diagnostic workflow based on a targeted next-generation sequencing panel of 86 genes causative of hereditary red blood cell defects. We obtained an overall diagnostic yield of 84% of the tested patients. Monogenic inheritance was seen for 69% (107/155), and multi-locus inheritance for 15% (23/155). PIEZO1 and SPTA1 were the most mutated loci. Accordingly, 16/23 patients with multi-locus inheritance showed dual molecular diagnosis of dehydrated hereditary stomatocytosis/xerocytosis and hereditary spherocytosis. These dual inheritance cases were fully characterized and were clinically indistinguishable from patients with hereditary spherocytosis. Additionally, their ektacytometry curves highlighted alterations of dual inheritance patients compared to both dehydrated hereditary stomatocytosis and hereditary spherocytosis. Our findings expand the genotypic spectrum of red blood cell disorders and indicate that multi-locus inheritance should be considered for analysis and counseling of these patients. Of note, the genetic testing was crucial for diagnosis of patients with a complex mode of inheritance.

Adjunctive treatment of clinically severe babesiosis with red blood cell exchange: a case series of nineteen patients

Transfusion ◽  
2019 ◽  
Vol 59 (8) ◽  
pp. 2629-2635 ◽  
Author(s):  
Christian P. Nixon ◽  
Sangshin Park ◽  
Christina E. Nixon ◽  
Rebecca M. Reece ◽  
Joseph D. Sweeney
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Case Series ◽  
Adjunctive Treatment

scholarly journals Combined spectrin and ankyrin deficiency is common in autosomal dominant hereditary spherocytosis

Blood ◽  
1993 ◽  
Vol 82 (10) ◽  
pp. 2953-2960 ◽  
Author(s):  
P Savvides ◽  
O Shalev ◽  
KM John ◽  
SE Lux
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Autosomal Dominant ◽  
Hereditary Spherocytosis ◽  
Band 3 ◽  
Normal Range ◽  
Dominant Form ◽  
Autosomal Dominant Form ◽  
The Common ◽  
Ankyrin Deficiency

Abstract The common autosomal dominant form of hereditary spherocytosis (HS) has been genetically linked to defects of the erythroid ankyrin gene in a few families; however, the frequency of ankyrin deficiency and its relationship to red blood cell (RBC) spectrin content are unknown. To test these questions, we measured RBC spectrin and ankyrin by radioimmunoassay in 39 patients from 20 families with dominant HS. Normal RBCs contained 242,000 +/- 20,500 spectrin heterodimers and 124,500 +/- 11,000 ankyrins per cell. In dominant HS, RBC spectrin and ankyrin ranged from about 40% to 100% of normal and were continuously distributed. Measurements in the same patient on different occasions were reproducible (+/- 5% to 10%) and RBCs from affected members of a kindred contained similar amounts of spectrin and ankyrin (+/- 3% to 4%). Spectrin and ankyrin levels were almost always less than the assay controls, but were less than the normal range in only 75% and 80% of kindreds, respectively. Remarkably, the degree of RBC spectrin and ankyrin deficiency was very similar in 19 of 20 HS kindreds. One otherwise typical family differed, with marked ankyrin deficiency (45% of control) and a relatively mild spectrin deficit (81%). We conclude that most patients with dominant HS have combined ankyrin and spectrin deficiency and that the two proteins are usually about equally deficient, suggesting that defects in ankyrin expression, ankyrin stability, or ankyrin band 3 (AE1) interactions may be common in dominant HS.

Red blood cell aquaporin-1 expression is decreased in hereditary spherocytosis

2016 ◽  
Vol 95 (10) ◽  
pp. 1595-1601 ◽  
Author(s):  
Renée L. Crisp ◽  
Romina E. Maltaneri ◽  
Daniela C. Vittori ◽  
Liliana Solari ◽  
Daniel Gammella ◽  
...  
Keyword(s):  
Blood Cell ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Aquaporin 1

Impact of red blood cell alloimmunization on sickle cell disease mortality: a case series

Transfusion ◽  
2015 ◽  
Vol 56 (1) ◽  
pp. 107-114 ◽  
Author(s):  
Robert Sheppard Nickel ◽  
Jeanne E. Hendrickson ◽  
Ross M. Fasano ◽  
Erin K. Meyer ◽  
Anne M. Winkler ◽  
...  
Keyword(s):  
Sickle Cell Disease ◽  
Blood Cell ◽  
Sickle Cell ◽  
Red Blood Cell ◽  
Case Series ◽  
Cell Disease ◽  
Disease Mortality

scholarly journals Case Report: Dacomitinib May Not Benefit Patients Who Develop Rare Compound Mutations After Later-Line Osimertinib Treatment

2021 ◽  
Vol 11 ◽  
Author(s):  
Hong-Shuai Li ◽  
Guang-Jian Yang ◽  
Yan Wang
Keyword(s):  
Case Series ◽  
Targeted Next Generation Sequencing ◽  
Free Dna ◽  
Case Series Study ◽  
Recurrent Mutations ◽  
Primary Drug Resistance ◽  
Potential Impact ◽  
Series Study ◽  
Generation Sequencing ◽  
Primary Drug

The acquired EGFR C797X mutation has been identified as the most notable resistance to osimertinib, and novel secondary mutations of EGFR L718 and L792 residues have also been demonstrated to confer osimertinib resistance, making the choice of medication after osimertinib treatment a quandary. Dacomitinib has been reported to have potential impact on patients acquiring rare compound mutations after osimertinib resistance; however, little evidence is available to date. In five lung adenocarcinoma patients resistant to later-line osimertinib, recurrent mutations at EGFR L792 and/or L718 were identified using targeted next-generation sequencing of tissue or cell-free DNA from plasma or pleural effusion. Dacomitinib was initiated after osimertinib resistance; however, all patients progressed within 2 months. Molecular structural simulation revealed that L792H + T790M and L718Q mutations could interfere with the binding of dacomitinib to EGFR and potentially cause primary drug resistance. Our case series study, to our knowledge, is the first to report the clinical efficacy of dacomitinib in patients harboring rare complex mutations after later-line osimertinib resistance.

Nitric Oxide Scavenging, Abnormal Vasoregulation and Oxidative Damage in sph/sph Mice with Severe Hereditary Spherocytosis: Possible Consequences of Red Blood Cell Hemolysis.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1660-1660
Author(s):  
Anne C. Schraufnagel ◽  
Barb Piknova ◽  
Kirkwood A. Pritchard ◽  
Neil Hogg ◽  
Nancy J. Wandersee
Keyword(s):  
Nitric Oxide ◽  
Blood Cell ◽  
Oxidative Damage ◽  
Xanthine Oxidase ◽  
Red Blood Cell ◽  
Hereditary Spherocytosis ◽  
Membrane Skeleton ◽  
Oxidative Enzymes ◽  
Endothelial Cell Function ◽  
Scavenging Capacity

Abstract The membrane skeleton, a multiprotein complex located just beneath the plasma membrane, provides the red blood cell (RBC) with the mechanical strength and deformability required to withstand high shear forces generated in the microcapillaries. Spectrin, a tetramer composed of a- and b- subunits, is the backbone of the erythroid membrane skeleton. Previously, we have shown that sph/sph mice have severe hereditary spherocytosis (HS) due to a spontaneous single-base deletion in the murine erythroid a-spectrin gene, Spna1. HS mice have severe hemolytic anemia, compensatory reticulocytosis, altered RBC morphology and increased fragility. Vascular dysfunction in sph/sph mice likely plays an important role in the mechanism by which these mice develop a high incidence of cardiac thrombosis and stroke between 6 and 12 weeks of age. We hypothesize that serum free hemoglobin released from intravascular hemolysis of sph/sph RBCs and xanthine oxidase, released from ischemic tissues, impairs endothelial cell function by scavenging nitric oxide (NO) and increasing oxidative damage. To test this hypothesis, we used helium electroparamagnetic resonance (EPR), to quantify plasma free Hb and NO scavenging capacity in the plasma of the mice; immunohistochemistry to determine tissue and vascular levels of xanthine oxidase and 3-nitrotyrosine; and, facialis arteries to measure changes in acetylcholine, endothelium and eNOS-dependent vasodilation. By EPR we found that the plasma free Hb and NO scavenging capacity in the plasma of sph/sph mice is much greater than that of the normal +/+ mice. Immunohistochemistry (IHC) for XO and NTyr revealed XO staining was decreased in livers of sph/sph mice as compared to livers from normal +/+ mice. XO staining was increased in local patches on the endothelium of lungs isolated from sph/sph mice compared to lungs from +/+ mice. NTyr, a marker of peroxynitrite formation was also increased in a focal manner in lungs of sph/sph mice compared to lungs of +/+ mice. Acetylcholine-induced and eNOS-dependent vasodilation in sph/sph mice was significantly impaired compared to vasodilation in normal +/+ mice. Taken together these data suggest the hemoglobin removal system in sph/sph mice is saturated, leading to increased free Hb and nitric oxide scavenging. IHC studies reveal XO is released from liver in sph/sph mice and once released binds the endothelium of lung, quite distal from the original site of injury. Such changes likely contribute to marked increases in NTyr staining and impaired endothelium and eNOS-dependent vasodilation in facialis arteries isolated from sph/sph mice. Taken together, these data indicate that sph/sph mice with severe HS have increased plasma free Hb and NO scavenging capacity as well as increased release of xanthine oxidase and subsequent binding to vascular endothelial cells to locations that are distal the original site of injury. Such plasma and vascular changes in hemoglobin and oxidative enzymes likely play a critical role in the mechanisms contributing to aberrant vasoregulation and initiating the pathways of oxidative damage found in sph/sph mice.

Diagnostic Yield of Cerebral Angiography in Patients With Computed Tomography-Negative, Lumbar Puncture-Positive Subarachnoid Hemorrhage

Neurosurgery ◽  
2013 ◽  
Vol 73 (2) ◽  
pp. 282-288 ◽  
Author(s):  
Nohra Chalouhi ◽  
Samantha Witte ◽  
David L. Penn ◽  
Pranay Soni ◽  
Robert M. Starke ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Subarachnoid Hemorrhage ◽  
Blood Cell ◽  
Lumbar Puncture ◽  
Red Blood Cell ◽  
Cerebral Angiography ◽  
Diagnostic Yield ◽  
Cerebral Aneurysms ◽  
Vascular Abnormality ◽  
Cell Counts

Abstract BACKGROUND: Cerebral angiography is generally recommended in patients with subarachnoid hemorrhage (SAH) by positive lumbar puncture (LP) but negative findings on computed tomography (CT). Existing data on the yield of angiography in these patients are very limited. OBJECTIVE: To retrospectively assess the diagnostic yield of cerebral angiography in patients with CT−/LP+ SAH and to determine the clinical and laboratory predictors of a vascular abnormality on angiography. METHODS: A total of 35 patients with CT−/LP+ SAH underwent cerebral angiography at our institution between 2008 and 2011. Patient clinical characteristics and LP findings were entered into a multivariate logistic regression analysis to identify predictors of vascular abnormalities. RESULTS: Twenty-five patients (71.4%) were female and 10 (28.6%) were male, with a mean age of 53 years. Twenty-six patients (74.3%) had cerebrospinal fluid xanthochromia. Sixteen patients (45.7%) were found to have an aneurysm on cerebral angiography. The median CSF red blood cell count of both the first (7790/mm3 vs 4700/mm3), and last collection tubes (6800/mm3 vs 3219/mm3) were higher in patients with cerebral aneurysms vs those without aneurysms (P = .3). On multivariate analysis, there were no clinical or laboratory parameters that predicted the presence of aneurysm on cerebral angiography. CONCLUSION: The diagnostic yield of cerebral angiography is high (45.7%) in patients with CT−/LP+ SAH. Higher red blood cell counts were noted in patients with cerebral aneurysms but no clinical or laboratory parameter can reliably predict the presence of a vascular anomaly. Thus, it is reasonable to perform cerebral angiography in all patients with CT−/LP+ SAH.

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