Genotype/phenotype correlation in hereditary spherocytosis

Iolascon, Achille; Avvisati, Rosa Anna

doi:10.3324/haematol.13344

Cited by 42 publications

(45 citation statements)

References 24 publications

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“…Ankyrin binds both spectrin and band 3, so ankyrin deficiency can cause a functional decrease in spectrin and band 3 proteins on the RBC membrane. 10 Combined ankyrin and spectrin deficiency was detected in most cases of HS. In these cases the ankyrin defect was the primary molecular defect and spectrin deficiency was secondary to the loss of ankyrin binding region.…”

Section: Discussionmentioning

confidence: 99%

“…For example, mutations of spectrin or ankyrin genes can cause a decrease in spectrin assembly on the RBC membrane. 10 After a large family carrying HS is detected, linkage analysis is the best pre-screening method to initially diagnose the molecular defect. DNA sequence analysis is the following step to detect the mutation in the defined gene.…”

Section: D14s1069mentioning

confidence: 99%

“…In HS, there is increased fragility of the red cell membrane, loss of membrane surface area, and trapping and destruction of the red cells in the spleen. 10 The molecular defect is highly heterogeneous, involving the genes encoding for spectrin, ankyrin, band 3 and protein 4.2.…”

Section: Introductionmentioning

confidence: 99%

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Linkage Analysis of Hereditary Spherocytosis in Four Generations of a Family with SPTB Gene Deficiency

Taşdemir¹

2012

UHOD

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Hereditary Spherocytosis (HS) is an inherited hemolytic anemia caused by the defects on membrane proteins and characterized by icterus, anemia and splenomegaly. Hereditary Spherocytosis clinically and genetically comprises a heterogeneous group of hemolytic anemias. In about 75% of the cases, the inheritance follows an autosomal dominant pattern and about 25% of cases occur sporadically. The aim of this study was to find which gene was responsible for the autosomal dominant HS in a large family of four generations. The linkage to the major HS genes (including SPTA1, SPTB, ANK1 ve SLC4A1) was searched by using LINKAGE and MERLIN analysis and LOD-score statistical calculations. As a result of using these analyses, we confirmed that the HS in this family was an autosomal dominant form of the disease and the incidence was linked to the SPTB gene which maps to chromosome 14. Linkage analysis is an effective prescreening method in genetically heterogeneous diseases and a new mutation analysis study is in the planning stage to detect the mutation in the SPTB gene. Keywords: Gene mapping, Hereditary spherocytosis, Linkage analysis, Spectrin ÖZET SPTB Gen Defekti Olan Dört Kuflakl› Herediter Sferositozlu Bir Ailede Ba¤lant› AnaliziHerediter sferositoz (HS), membran proteinlerinin defektleri nedeniyle oluflan; anemi, sar›l›k ve splenomegali ile karakterize herediter bir hastal›kt›r. HS, klinik ve genetik olarak hem dominant hem de resesif kal›t›mla iliflkili heterojen bir hastal›kt›r. Olgular›n % 75'i otozomal dominantt›r, % 25 olguda ise bir aile hikayesi yoktur. Bu çal›flman›n amac› dört kuflakl› genifl bir ailede rastlanan otozomal dominant geçiflli Herediter sferositoz'da hangi gendeki mutasyonun patolojiden sorumlu oldu¤unu bulmakt›r. Herediter sferositoz'da majör etkili olan SPTA1, SPTB, ANK1 ve SLC4A1 genlerine ba¤lant›n›n varl›¤›; ba¤lant› (LINKAGE) ve MERLIN analizi ayr›ca LOD skor istatistiksel hesaplamalar› kullan›larak araflt›r›lm›flt›r. Sonuç olarak; bu analizlerin kullan›m› ile araflt›rd›¤›m›z ailede görülen Herediter Sferositoz'un otozomal dominant olarak kal›t›ld›¤› ve 14 numaral› kromozomda yerleflik olan SPTB geninin hastal›ktan sorumlu olaca-¤› bulunmufltur. Genetik heterojenite gözlenen hastal›klarda ba¤lant› analizi, etkin bir ön tarama yoludur ve ba¤lant› gözlenen SPTB geninde mutasyon taramas› yap›labilmesi için yeni bir çal›flma planlanacakt›r.

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Section: Discussionmentioning

confidence: 99%

Section: D14s1069mentioning

confidence: 99%

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Linkage Analysis of Hereditary Spherocytosis in Four Generations of a Family with SPTB Gene Deficiency

Taşdemir¹

2012

UHOD

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“…41 Sin embargo, ninguna de estas pruebas puede detectar el 100% de los pacientes. 6,13,50,[55][56][57] La fragilidad osmótica eritrocitaria (FOE), que da resultados positivos en aproximadamente 80% de los pacientes, 8,15,58 es aún considerada el "patrón oro" por algunos autores, 50,55,59 realizada simultáneamente con la autohemólisis (AH), aunque no sirve para diferenciar ESH de la esferocitosis secundaria a otras patologías, como anemia hemolítica autoinmune (AHAI), enfermedad hemolítica del recién nacido por incompatibilidad ABO (EHRN-ABO) o eliptocitosis hereditaria esferocítica. 59,60 Actualmente, se dispone de nuevas pruebas diagnósticas, más específicas y sensibles, que presentan, además, la ventaja de requerir menor cantidad de sangre para el procesamiento.…”

Section: Figura 3 Prevalencia De Deficiencias De Proteínas De Membraunclassified

“…13 La sensibilidad y especificidad de las pruebas arriba descritas varían según los distintos autores. Como ninguna de ellas es positiva en 100% de los casos, 31,[49][50][51]55,62 en la práctica clínica, cada laboratorio estudia al paciente con una pequeña batería de pruebas, de acuerdo con la sensibilidad y especificidad propias alcanzadas con cada una de ellas y con la disponibilidad de equipos y reactivos. Las pruebas más recomendadas actualmente son la 5'EMA-CF y la CH, ya que han demostrado alta sensibilidad y especificidad.…”

Section: Control Normalunclassified

Esferocitosis hereditaria. Revisión. Parte I. Historia, demografía, etiopatogenia y diagnóstico

Hematología¹,

Donato²,

Crisp³

et al. 2015

Arch Argent Pediat

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Neonatal anemia: Revisiting the enigmatic pyknocyte

Nassin

Vergilio²,

Heeney

et al. 2017

American J Hematol

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A 27-day-old, former 31-week, fraternal twin male infant in the neonatal intensive care unit (NICU) was born to a 34-year old gravida 2 para 0 female via cesarean section following spontaneous premature rupture of amniotic membranes. The amniotic fluid was clear and showed no signs of infection or meconium. The mother was blood type O, Rh positive. The patient's Apgar scores at 1 and 5 minutes were 9 and 9 respectively. Physical examination and medical course were unremarkable. Blood cultures were negative and empiric antibiotics were discontinued after 48 hours.On day of life (DOL) 25 the patient's hematocrit (Hct) was 25.5% with an elevated reticulocyte percent (6.4%), unconjugated bilirubin 13.5 mg/dL, and conjugated bilirubin 0.6 mg/dL. Pediatric hematology was consulted on DOL 27 for worsening anemia with increasing reticulocytosis and unconjugated hyperbilirubinemia despite aggressive phototherapy. There was no hematuria, petechiae, ecchymosis, abdominal distention, fever, hematochezia, or cardiorespiratory instability. The patient had not received a red cell transfusion. Parents were nonconsanguineous, Greek Americans without personal or family history of hematologic disorders including cholelithiasis or splenectomy. The patient appeared pale and jaundiced, but in no distress. His exam showed no organomegaly and was overall normal. Laboratory results revealed total bilirubin 9.2 mg/dL, direct bilirubin 0.5 mg/dL, hematocrit 24.8% and reticulocyte count 18.9%. Urinalysis showed 11 blood without formal microscopic analysis. Newborn screen results demonstrated hemoglobin (Hgb) FA by isoelectric focusing. Table 1. Full longitudinal laboratory values are depicted inNeonatal hyperbilirubinemia can be a common and benign problem in full term neonates. 1 Hyperbilirubinemia during the first week of life is more common in premature infants, occurring in up to 80% versus 60% of term infants. 2 However, hyperbilirubinemia in the first 24 hours of life is almost always pathologic. 3 Bilirubin is the product of heme catabolism in the reticuloendothelial system and is cleared via conjugation in the liver followed by secretion in the bile. Transient physiologic hyperbilirubinemia in neonates is commonly the result of increased red blood cell turnover in combination with transient deficiency in uridine diphosphosphate glucuronosyltransferase (UGT)1A1, the enzyme responsible for hepatic bilirubin conjugation. 4 Additionally, neonates have increased enterohepatic circulation compared to children and adults because their gastrointestinal tracts lack bacteria necessary for conversion of bilirubin conjugates into urobilinoids, which are not reabsorbed by the intestine. Therefore, neonates not only have a higher bilirubin burden and decreased ability for conjugation, but they are also more prone to increased enteric reabsorption. 5 Physiologic hyperbilirubinemia can be exacerbated with breastfeeding if the neonate is mildly dehydrated until milk production increases. As a result, infants receive fewer calories, a further stimulu...

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Genotype/phenotype correlation in hereditary spherocytosis

Cited by 42 publications

References 24 publications

Linkage Analysis of Hereditary Spherocytosis in Four Generations of a Family with SPTB Gene Deficiency

Linkage Analysis of Hereditary Spherocytosis in Four Generations of a Family with SPTB Gene Deficiency

Esferocitosis hereditaria. Revisión. Parte I. Historia, demografía, etiopatogenia y diagnóstico

Neonatal anemia: Revisiting the enigmatic pyknocyte

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