Genotype Phenotype Correlation in Thalassemia Syndromes and Their Correlation with Xmn-1 Polymorphism.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 3845-3845
Author(s):  
Anupam Sachdeva ◽  
Aditya Raina ◽  
Varinder Kumar Khanna ◽  
Subhash Chander Arya ◽  
Satya Prakash Yadav ◽  
...  
Keyword(s):  
Blood Group ◽  
Genetic Diseases ◽  
Clinical Manifestations ◽  
Age At Diagnosis ◽  
Beta Thalassemia ◽  
Clinical Parameters ◽  
Phenotype Correlation ◽  
Inherited Disorders ◽  
Genotype Phenotype Correlation ◽  
High Degree

Abstract Among the inherited disorders of blood, thalassemia constitutes a major bulk of genetic diseases in India. It causes a high degree of morbidity. In a study conducted in India it has been estimated that there is a frequency of 1:2700 at the time of birth. Thus on an average 9000 new thalassemics are born every year in India.. The present study has been aimed at investigating the clinical and hematological spectrum in the above syndrome. It also assessed the prevalence of Xmn -1 polymorphism its relationship with various mutations and its role in modifying the clinical manifestations. The study was conducted on fifty patients representing 49 families and consisting of 33 males and 17 females who were homozygous for beta thalassemia and ranged in age from 3 months to 32 years. The patients were screened for common Indian mutations and their Xmn polymorphism status and this was correlated with their clinical parameters. Apositive correlation in presence of Xmn-1 polymorphism and IVS1-1 mutation was noted. There was also a correlation between age at diagnosis and also the age at first transfusion. There was a correlation between Xmn polymorphism and IVS1-1 mutation. This was found most commonly in the Punjabi Khatri community. None of the patients with blood group O had positivity of Xmn polymorphism. There was no correlation between Xmn and hemoglobin at diagnosis, HbF at diagnosis, MCV at diagnosis, amount of blood in mL/Kg/year and sex and religion.

Genotype–phenotype correlation related to lipid profile in beta-thalassemia major and intermedia in southern Iran

2012 ◽  
Vol 6 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Mohammadreza Bordbar ◽  
Sezaneh Haghpanah ◽  
Abdolreza Afrasiabi ◽  
Javad Dehbozorgian ◽  
Mehran Karimi
Keyword(s):  
Lipid Profile ◽  
Thalassemia Major ◽  
Beta Thalassemia ◽  
Phenotype Correlation ◽  
Beta Thalassemia Major ◽  
Southern Iran ◽  
Genotype Phenotype Correlation

scholarly journals Genotype-Phenotype Correlation in Patients with Congenital Adrenal Hyperplasia due to 21-Hydroxylase Deficiency in Cuba

2021 ◽  
Vol 2021 ◽  
pp. 1-6
Author(s):  
Tania Mayvel Espinosa Reyes ◽  
Teresa Collazo Mesa ◽  
Paulina Arasely Lantigua Cruz ◽  
Adriana Agramonte Machado ◽  
Emma Domínguez Alonso ◽  
...  
Keyword(s):  
Congenital Adrenal Hyperplasia ◽  
Point Mutations ◽  
Clinical Manifestations ◽  
Adrenal Hyperplasia ◽  
Phenotype Correlation ◽  
Hydroxylase Deficiency ◽  
Cyp21a2 Gene ◽  
Genotype Phenotype Correlation ◽  
21 Hydroxylase Deficiency ◽  
Cuban Population

Background. There are several studies that show a good genotype-phenotype correlation in congenital adrenal hyperplasia (CAH) due to 21-hydroxylase deficiency (21OHD). However, there is well-documented evidence of inconsistency in some cases. Objectives. To determine if there is a correlation between the identified mutations and the clinical manifestations of 21OHD in the Cuban population. Methods. A cross-sectional descriptive study of all patients referred for a molecular diagnosis of 21OHD in Cuba from January 2000 to December 2018. The clinical manifestations of each patient were identified and classified according to the phenotype. The CYP21A2 gene was analyzed for the presence of 5 point mutations involved in the pathogenesis of 21OHD (intron 2, deletion of 8bp, I172N, P30L, and Q318X); correlation was sought between the phenotypic characteristics and the frequencies of point mutations in the patients using the Spearman test. Results. A total of 55 patients underwent direct analysis of the CYP21A2 gene in order to determine the presence of the 5 point mutations. Point mutations were identified in 31 patients, which corresponded to 56%. A statistically significant genotype-phenotype correlation was found. Conclusions. The correlation between the detected molecular defect and the clinical expression of 21OHD was reasonable in the Cuban population, which could allow phenotypic predictions to be made from the genotype.

scholarly journals Genetic and clinical characterization of 73 Pigmentary Mosaicism patients: revealing the genetic basis of clinical manifestations

2019 ◽  
Vol 14 (1) ◽  
Author(s):  
C. Salas-Labadía ◽  
S. Gómez-Carmona ◽  
R. Cruz-Alcívar ◽  
D. Martínez-Anaya ◽  
V. Del Castillo-Ruiz ◽  
...  
Keyword(s):  
Snp Array ◽  
Clinical Manifestations ◽  
Frequent Pattern ◽  
Phenotype Correlation ◽  
Molecular Abnormalities ◽  
Genotype Phenotype Correlation ◽  
Analysis Strategy ◽  
Pigmentary Mosaicism ◽  
Different Tissues

Abstract Background Pigmentary mosaicism constitutes a heterogeneous group of skin pigmentation alterations associated with multisystem involvement. The aim of this study was to establish a complete cytogenetic and molecular characterization of PM patients, emphasizing on searching for possible low chromosomal mosaicism and on establishing an accurate genotype-phenotype correlation. Results A total of 73 patients were included (3 months to 18 years of age), 52% male and 48% female. Observed in 69 (95%) patients, the most frequent pattern of pigmentation was fine and whorled BL, which was associated with disseminated skin extent in 41 (59%) patients. Central nervous system (84%) alterations were the most frequent observed in the group of patients, followed by the musculoskeletal (53%) and ophthalmologic (27%) alterations. Considering the pattern of pigmentation, no significant differences in association with skin extent or extracutaneous manifestations were detected. Following a strict cytogenetic analysis strategy, screening metaphases from three different tissues (peripheral blood, hyperpigmented and hypopigmented skin) we found that 23/73 patients had chromosomal abnormalities classified as follows: 1) Mosaic with 2 or more different cell lines with structural alterations n = 19; 2) Polyploidy (mosaic) n = 1 and 3) Alterations in all cells in three different tissues n = 3. SNP array, array CGH and FISH were useful for the complete characterization of the chromosomal aberrations, for the detection of microdeletions in patients with normal karyotype but with strong clinical suspicious of chromosomal alteration, and for a better establishment of genotype-phenotype correlation. In 2 patients we found genes associated with some of the extracutaneous manifestations (SHH, MNX1, PPP2R2C). Conclusions This group of 73 patients finely described is the largest series of patients with pigmentary mosaicism reported worldwide. As we showed in this study, the followed analysis strategy allowed the detection of cytogenetic and molecular abnormalities, and made possible the establishment of genotype-phenotype associations in some patients. An important limitation of our study was the analysis of fibroblasts cultures instead of melanocytes and keratinocytes. In some cases the direct molecular DNA analysis of skin biopsy could be another choice.

scholarly journals MODULATING EFFECT OF THE −158 GΓ (C→T) XMN-1 POLYMORPHISM IN INDIAN SICKLE CELL PATIENTS

2012 ◽  
Vol 4 (1) ◽  
pp. e2012001 ◽  
Author(s):  
Sanjay Pandey ◽  
Sweta Pandey ◽  
Rahasya Mani Mishra ◽  
Renu Saxena
Keyword(s):  
Sickle Cell ◽  
Hematological Parameters ◽  
Genetic Diseases ◽  
Beta Thalassemia ◽  
P Value ◽  
Polymorphism Analysis ◽  
Inherited Disorders ◽  
Pcr Rflp ◽  
Hbf Level

Xmn-1 polymorphism is a known factor, which increases fetal haemoglobin production. Among the inherited disorders of blood, thalassaemia and SCD constitutes a major bulk of genetic diseases in India.  Our aim was to verify the role of the Xmn I polymorphism as a modulating factor in sickle cell patients and frequency of the polymorphism in Indian sickle cell patients. Subjects were 60 sickles homozygous and 75 sickle beta thalassemia patients. 5 ml blood   samples collected from patients. Screening of sickle patients done by HPLC. An automated cell analyzer SYSMEX (K-4500 Model) used to analyze the CBC of patients.Xmn1 polymorphism analysis done by PCR-RFLP and Statistical analysis was performed on GraphPad static’s software. t test applied to compare the means amongst group. Among the sickle homozygous 27 were   heterozygous (+/-) and 19 were   homozygous (+/+) while 30 were heterozygous and 24 were homozygous in sickle β-thalassemia patients. Extremely significant differences (p-value <0.001) of hematological parameters seen among patient with xmn-1 carrier and without the xmn-1 carrier. In our cases the clinical symptom less frequent and higher HbF level with Xmn-1 carriers. Presence of Xmn-1 polymorphism in sickle patients with higher HbF that improve phenotypic presentation in the sickle cell patients. We conclude that the phenotype of Indian sickle cell patients influenced by Xmn-1 polymorphism.

scholarly journals Case Report: Amyloidosis Cutis Dyschromica: Dermoscopy and Reflectance Confocal Microscopy and Gene Mutation Analysis of a Chinese Pedigree

2021 ◽  
Vol 8 ◽  
Author(s):  
Hui Wang ◽  
Zhenyu Zhong ◽  
Xiuli Wang ◽  
Liyun Zheng ◽  
Yifan Wang ◽  
...  
Keyword(s):  
Confocal Microscopy ◽  
Clinical Manifestations ◽  
Gene Mutations ◽  
Reflectance Confocal Microscopy ◽  
Pathological Examination ◽  
Missense Mutations ◽  
Phenotype Correlation ◽  
Rare Type ◽  
Genotype Phenotype Correlation ◽  
Imaging Characteristics

Background: Amyloidosis cutis dyschromica (ACD) is a rare type of primary localized cutaneous amyloidosis. Non-invasive techniques can provide important clues for early diagnosis.Objectives: To highlight the characteristic imaging changes of ACD under dermoscopy and reflectance confocal microscopy (RCM), investigate gene mutations in a Chinese Han pedigree of ACD, and analyze the genotype–phenotype correlation.Methods: Dermoscopy and RCM examinations were completed together for the pedigree, and the imaging characteristics were described. The diagnosis of ACD was confirmed by pathological examination. Sequencing was performed followed by bioinformatics and genotype–phenotype correlation. ACD-related articles published on PubMed between January 1970 and March 2021 were reviewed and summarized.Results: In ACD, dermoscopy showed patchy white hypopigmentation and brownish spots, stripes, or hyperpigmented blotches and patches. RCM showed a highly refractive substance with clumpy, dotted, and linear structures inside the papillary dermis. Sequencing identified glycoprotein non-metastatic melanoma protein B (GPNMB) missense mutations [c.393T&gt;G (p.Y131X; NM_001005340.2)] and a frameshift deletion mutation [c.719_720delTG (p.V240fs; NM_001005340.2)]. The ANNOtate VARiation (ANNOVAR) software predicted that c.393T&gt;G is a pathogenic mutation. The literature review found 14 mutations, namely, 5 (35.7%) frameshift mutations, 4 (28.6%) non-sense mutations, 4 (28.6%) missense mutations, and 1 (7.1%) splice site mutation. Blisters and epidermolysis were observed in several cases, but there was no significant association between clinical manifestations and mutations in ACD.Conclusions: This study was the first to combine dermoscopy and RCM to describe ACD. Two GPNMB gene mutations were reported in a Chinese ACD pedigree. The genotype–phenotype correlation was analyzed for the first time; however, there was no significant correlation.

scholarly journals Hepatocellular carcinoma in adult thalassemia patients: an expert opinion based on current evidence

2020 ◽  
Vol 20 (1) ◽  
Author(s):  
Alessandra Mangia ◽  
Davide Bellini ◽  
Umberto Cillo ◽  
Andrea Laghi ◽  
Giuseppe Pelle ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Genetic Diseases ◽  
Current Evidence ◽  
Beta Thalassemia ◽  
Inherited Disorders ◽  
Modified Delphi ◽  
Expert Opinions ◽  
Delphi Approach ◽  
Randomized Controlled Studies ◽  
Increased Risk

AbstractBeta-thalassemia represents a heterogeneous group of haemoglobin inherited disorders, among the most common genetic diseases in the world, frequent in the Mediterranean basin. As beta-thalassemia patients’ survival has increased over time, previously unknown complications are observed with increasing frequency. Among them, an increased risk of hepatocellular carcinoma (HCC) has been registered. Our aim is to reduce inequalities in diagnosis and treatment and to offer patients univocal recommendations in any institution.The members of the panel - gastroenterologists, radiologists, surgeons and oncologists -were selected on the basis of their publication records and expertise. Thirteen clinical questions, derived from clinical needs, and an integration of all the committee members’ suggestions, were formulated. Modified Delphi approach involving a detailed literature review and the collective judgement of experts, was applied to this work.Thirteen statements were derived from expert opinions’ based on the current literature, on recently developed reviews and on technological advancements. Each statement is discussed in a short paragraph reporting the current key evidence. As this is an emerging issue, the number of papers on HCC in beta-thalassemia patients is limited and based on anecdotal cases rather than on randomized controlled studies. Therefore, the panel has discussed, step by step, the possible differences between beta-thalassemia and non beta-thalassemia patients. Despite the paucity of the literature, practical and concise statements were generated.This paper offers a practical guide organized by statements describing how to manage HCC in patients with beta-thalassemia.

scholarly journals The Prevalence of Clinical Features in Patients with Aarskog–Scott Syndrome and Assessment of Genotype-Phenotype Correlation: A Systematic Review

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Victor Zanetti Drumond ◽  
Lucas Sousa Salgado ◽  
Camila Sousa Salgado ◽  
Vitor Augusto de Lima Oliveira ◽  
Eliene Magda de Assis ◽  
...  
Keyword(s):  
Systematic Review ◽  
Clinical Features ◽  
Clinical Manifestations ◽  
Rare Condition ◽  
Clinical Findings ◽  
Pathogenic Variant ◽  
Genitourinary Tract ◽  
Direct Relation ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation

Aarskog–Scott syndrome is a genetically and clinically heterogeneous rare condition caused by a pathogenic variant in the FGD1 gene. A systematic review was carried out to analyse the prevalence of clinical manifestations found in patients, as well as to evaluate the genotype-phenotype correlation. The results obtained show that clinical findings of the craniofacial, orthopaedic, and genitourinary tract correspond to the highest scores of prevalence. The authors reclassified the primary, secondary, and additional criteria based on their prevalence. Furthermore, it was possible to observe, in accordance with previous reports, that the reported phenotypes do not present a direct relation to the underlying genotypes.

scholarly journals Clinical Manifestations in a Girl with NAA10-Related Syndrome and Genotype–Phenotype Correlation in Females

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 900
Author(s):  
Ilenia Maini ◽  
Stefano G. Caraffi ◽  
Francesca Peluso ◽  
Lara Valeri ◽  
Davide Nicoli ◽  
...  
Keyword(s):  
De Novo ◽  
Clinical Manifestations ◽  
Growth Failure ◽  
Autistic Traits ◽  
Missense Variant ◽  
Postnatal Growth ◽  
Young Female ◽  
Phenotype Correlation ◽  
Genotype Phenotype Correlation ◽  
Clinical Description

Since 2011, eight males with an X-linked recessive disorder (Ogden syndrome, MIM #300855) associated with the same missense variant p.(Ser37Pro) in the NAA10 gene have been described. After the advent of whole exome sequencing, many NAA10 variants have been reported as causative of syndromic or non-syndromic intellectual disability in both males and females. The NAA10 gene lies in the Xq28 region and encodes the catalytic subunit of the major N-terminal acetyltransferase complex NatA, which acetylates almost half the human proteome. Here, we present a young female carrying a de novo NAA10 [NM_003491:c.247C > T, p.(Arg83Cys)] variant. The 18-year-old girl has severely delayed motor and language development, autistic traits, postnatal growth failure, facial dysmorphisms, interventricular septal defect, neuroimaging anomalies and epilepsy. Our attempt is to expand and compare genotype–phenotype correlation in females with NAA10-related syndrome. A detailed clinical description could have relevant consequences for the clinical management of known and newly identified individuals.

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