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Luigi Laino - One of the best experts on this subject based on the ideXlab platform.
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prenatal diagnosis and post mortem examination in a fetus with thrombocytopenia absent radius tar syndrome due to Compound Heterozygosity for a 1q21 1 microdeletion and a rbm8a hypomorphic allele a case report
BMC Research Notes, 2013Co-Authors: Irene Bottillo, Romano Fabbri, Nicoletta Preziosi, Giovanna Scassellati, Evelina Silvestri, Marco Castori, Carmelilia De Bernardo, Barbara Grammatico, Antonella Spagnuolo, Luigi LainoAbstract:Thrombocytopenia–absent radius syndrome is a rare autosomal recessive disorder characterized by megakaryocytic thrombocytopenia and longitudinal limb deficiencies mostly affecting the radial ray. Most patients are Compound heterozygotes for a 200 kb interstitial microdeletion in 1q21.1 and a hypomorphic allele in RBM8A, mapping in the deleted segment. At the moment, the complete molecular characterization of thrombocytopenia–absent radius syndrome is limited to a handful of patients mostly ascertained in the pediatric age We report on a fetus with bilateral upper limb deficiency found at standard prenatal ultrasound examination. The fetus had bilateral radial agenesis and humeral hypo/aplasia with intact thumbs, micrognathia and urinary anomalies, indicating thrombocytopenia–absent radius syndrome. Molecular studies demonstrated Compound Heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant at the hemizygous state, inherited from the mother and father, respectively The molecular information allowed prenatal diagnosis in the following pregnancy resulting in the birth of a healthy carrier female. A review was carried out with the attempt to the trace the fetal ultrasound presentation of thrombocytopenia–absent radius syndrome and discussing opportunities for second-tier molecular studies within a multidisciplinary setting.
Jean Delaunay - One of the best experts on this subject based on the ideXlab platform.
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molecular analysis of 42 patients with congenital dyserythropoietic anemia type ii new mutations in the sec23b gene and a search for a genotype phenotype relationship
Haematologica, 2010Co-Authors: Achille Iolascon, Roberta Russo, Maria Rosaria Esposito, Silverio Perrotta, Roberta Asci, Carmelo Piscopo, Madeleine Feneantthibault, Loic Garcon, Jean DelaunayAbstract:Background The most frequent form of congenital dyserythropoietic anemia is the type II form. Recently it was shown that the vast majority of patients with congenital dyserythropoietic anemia type II carry mutations in the SEC23B gene. Here we established the molecular basis of 42 cases of congenital dyserythropoietic anemia type II and attempted to define a genotype-phenotype relationship. Design and Methods SEC23B gene sequencing analysis was performed to assess the diversity and incidence of each mutation in 42 patients with congenital dyserythropoietic anemia type II (25 described exclusively in this work), from the Italian and the French Registries, and the relationship of these mutations with the clinical presentation. To this purpose, we divided the patients into two groups: (i) patients with two missense mutations and (ii) patients with one nonsense and one missense mutation. Results We found 22 mutations of uneven frequency, including seven novel mutations. Compound Heterozygosity for a missense and a nonsense mutation tended to produce a more severe clinical presentation, a lower reticulocyte count, a higher serum ferritin level, and, in some cases, more pronounced transfusion needs, than homozygosity or Compound Heterozygosity for two missense mutations. Homozygosity or Compound Heterozygosity for two nonsense mutations was never found. Conclusions This study allowed us to determine the most frequent mutations in patients with congenital dyserythropoietic anemia type II. Correlations between the mutations and various biological parameters suggested that the association of one missense mutation and one nonsense mutation was significantly more deleterious that the association of two missense mutations. However, there was an overlap between the two categories.
Irene Bottillo - One of the best experts on this subject based on the ideXlab platform.
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prenatal diagnosis and post mortem examination in a fetus with thrombocytopenia absent radius tar syndrome due to Compound Heterozygosity for a 1q21 1 microdeletion and a rbm8a hypomorphic allele a case report
BMC Research Notes, 2013Co-Authors: Irene Bottillo, Romano Fabbri, Nicoletta Preziosi, Giovanna Scassellati, Evelina Silvestri, Marco Castori, Carmelilia De Bernardo, Barbara Grammatico, Antonella Spagnuolo, Luigi LainoAbstract:Thrombocytopenia–absent radius syndrome is a rare autosomal recessive disorder characterized by megakaryocytic thrombocytopenia and longitudinal limb deficiencies mostly affecting the radial ray. Most patients are Compound heterozygotes for a 200 kb interstitial microdeletion in 1q21.1 and a hypomorphic allele in RBM8A, mapping in the deleted segment. At the moment, the complete molecular characterization of thrombocytopenia–absent radius syndrome is limited to a handful of patients mostly ascertained in the pediatric age We report on a fetus with bilateral upper limb deficiency found at standard prenatal ultrasound examination. The fetus had bilateral radial agenesis and humeral hypo/aplasia with intact thumbs, micrognathia and urinary anomalies, indicating thrombocytopenia–absent radius syndrome. Molecular studies demonstrated Compound Heterozygosity for the 1q21.1 microdeletion and the RBM8A rs139428292 variant at the hemizygous state, inherited from the mother and father, respectively The molecular information allowed prenatal diagnosis in the following pregnancy resulting in the birth of a healthy carrier female. A review was carried out with the attempt to the trace the fetal ultrasound presentation of thrombocytopenia–absent radius syndrome and discussing opportunities for second-tier molecular studies within a multidisciplinary setting.
Maarten Jansen - One of the best experts on this subject based on the ideXlab platform.
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combined pituitary hormone deficiency caused by Compound Heterozygosity for two novel mutations in the pou domain of the pit1 pou1f1 gene
The Journal of Clinical Endocrinology and Metabolism, 2001Co-Authors: Brenda I Hendriksstegeman, Kevin D Augustijn, Bert Bakker, Pieternella Holthuizen, Peter C Van Der Vliet, Maarten JansenAbstract:The POU homeodomain containing transcriptional activator POU1F1, formerly called Pit1 or GHF-1, is required for the embryological determination and postnatal secretory function of the GH-, PRL-, and TSH-producing cells in the anterior pituitary. Several mutations in the gene encoding POU1F1 have been described, resulting in a syndrome of combined pituitary hormone deficiency involving these three hormones. Most of the patients with this phenotype have either a dominant negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation in the POU1F1 gene; to date only one case has been reported with Compound Heterozygosity for two point mutations. Here, we describe a boy with severe deficiencies of GH, PRL, and TSH who had Compound Heterozygosity for two novel point mutations in the POU1F1 gene: a 1-bp deletion frameshift mutation (747delA), the first one described to date in this gene, which leads to a nonfunctional truncated protein lacking the entire DNA recognition helix of the POU homeo...
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combined pituitary hormone deficiency caused by Compound Heterozygosity for two novel mutations in the pou domain of the pit1 pou1f1 gene
The Journal of Clinical Endocrinology and Metabolism, 2001Co-Authors: Brenda I Hendriksstegeman, Kevin D Augustijn, Bert Bakker, Pieternella Holthuizen, Peter C Van Der Vliet, Maarten JansenAbstract:The POU homeodomain containing transcriptional activator POU1F1, formerly called Pit1 or GHF-1, is required for the embryological determination and postnatal secretory function of the GH-, PRL-, and TSH-producing cells in the anterior pituitary. Several mutations in the gene encoding POU1F1 have been described, resulting in a syndrome of combined pituitary hormone deficiency involving these three hormones. Most of the patients with this phenotype have either a dominant negative mutation in codon 271 (R271W) or are homozygous for a recessive mutation in the POU1F1 gene; to date only one case has been reported with Compound Heterozygosity for two point mutations. Here, we describe a boy with severe deficiencies of GH, PRL, and TSH who had Compound Heterozygosity for two novel point mutations in the POU1F1 gene: a 1-bp deletion frameshift mutation (747delA), the first one described to date in this gene, which leads to a nonfunctional truncated protein lacking the entire DNA recognition helix of the POU homeodomain, and a missense mutation in the C-terminal end of the fourth alpha-helix of the POU-specific domain (W193R),which causes a 500-fold reduction in the ability to bind to DNA and activate transcription.
Guinian Huang - One of the best experts on this subject based on the ideXlab platform.
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Compound Heterozygosity for two novel mutations of the sec23b gene in congenital dyserythropoietic anemia type ii
International Journal of Hematology, 2021Co-Authors: Shanshan Chen, Ziwen Guo, Shanhong Yang, Guinian HuangAbstract:Congenital dyserythropoietic anemia type II (CDA II), a rare genetic disorder, results from SEC23B gene mutations according to previous studies. Here, we present a case of CDA II involving two novel pathogenic mutations of SEC23B that have not previously been reported. The patient suffered from jaundice, tea-colored urine, and weakness. Laboratory data indicated moderately decreased hemoglobin, iron overload, and abnormal erythroblast morphology. Therefore, a diagnosis of CDA II was considered. Peripheral blood samples were used to perform whole exome sequencing, and the results showed Compound Heterozygosity of the SEC23B gene with the following mutations: c.1162T>A (p.F388I) and c.1603delC (p.R535del). The mutant proteins were predicted to be deleterious and resulted in decreased structural stability. PyMOL software was used to analyze the structural change caused by the p.F388I missense mutation, and the results indicated a deficiency in π-π interactions. In conclusion, our report extends the mutation spectrum of SEC23B in the diagnosis of CDA II.