Biochemical and genetic characterization of 16 patients with propionic acidemia

2021 ◽  
pp. 3-14
Author(s):  
А.С. Галушкин ◽  
Е.Ю. Пыркова ◽  
М.В. Куркина ◽  
С.В. Михайлова ◽  
В.П. Воронцова ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
3D Model ◽  
Genetic Characterization ◽  
Propionic Acidemia ◽  
Medical Genetics ◽  
Organic Acidemia ◽  
Biochemical Tests ◽  
Genetics And Genomics ◽  
Hydroxypropionic Acid

Пропионовая ацидемия (ПА) - редкое наследственное заболевание с аутосомно-рецессивным типом наследования, относится к «классическим», т.е. наиболее часто диагностируемым органическим ацидемиям. В данной работе представлена биохимическая и молекулярно-генетическая характеристика 16 пациентов с ПА, выявленных в Российской Федерации. У большинства обследованных пациентов первые симптомы проявились в первые месяцы жизни, наиболее частые из них: нарушения вскармливания, судороги, мышечная гипотония, угнетение сознания. При биохимическом исследовании (ГХ-МС и МС/МС) у пациентов было выявлено повышение концентрации 3-гидроксипропионой кислоты, метилцитрата, пропионилглицина, C3, глицина, которые являются патогномоничными маркерами этой патологии. В результате молекулярно-генетического анализа в генах PCCA и PCCB было выявлено 6 неописанных ранее вариантов нуклеотидной последовательности (4 варианта в гене PCCA, 2 - в гене PCCB), один из которых (PCCB: c.655-2A>G) имеет высокую частоту (17,2%, 5/29 мутантных аллелей генов PCCA и PCCB) в исследуемой выборке. Локализация миссенс-вариантов и их влияние на структуру белка были продемонстрированы на 3D-модели фермента пропионил-КоА-карбоксилазы. Выявленным вариантам были присвоены критерии патогенности в соответствии с рекомендациями American College of Medical Genetics and Genomics (ACMG). Propionic acidemia is a rare autosomal recessive metabolic disorder, characterized as classic organic acidemia. The article represents biochemical and molecular characterization of 16 patients diagnosed with propionic acidemia in Russia. Symptoms appeared during the first months after birth in most cases. Poor feeding, seizures, hypotonia, lethargy were the most frequent symptoms. Biochemical tests (GC-MS and MS/MS) showed elevated 3-hydroxypropionic acid, methylcitrate, propionylglycine, C3 in patients blood. Six undescribed earlier variants were found as a result of PCCA & PCCB (4 variants - PCCA, 2 - PCCB) genes DNA-tests. Variant c.655-2A>G in PCCB is the most frequent in this group (17.2%). Localization of missense variants and their effect on protein was demonstrated using propionyl-CoA carboxylase 3D model. New variants were classified according to the American College of Medical Genetics and Genomics (ACMG) guidelines.

Clinical and Genetic Characterization of Autosomal Recessive Spinocerebellar Ataxia Type 16 (SCAR16) in Taiwan

2020 ◽  
Vol 19 (4) ◽  
pp. 544-549 ◽  
Author(s):  
Hsu-Huai Chiu ◽  
Cheng-Tsung Hsaio ◽  
Yu-Shuen Tsai ◽  
Yi-Chu Liao ◽  
Yi-Chung Lee ◽  
...  
Keyword(s):  
Spinocerebellar Ataxia ◽  
Autosomal Recessive ◽  
Genetic Characterization ◽  
Spinocerebellar Ataxia Type

scholarly journals 11β-hydroxylase deficiency disorders

2018 ◽  
Vol 15 (2) ◽  
pp. 197-209
Author(s):  
Nguyễn Thị Phương Mai ◽  
Nông Văn Hải ◽  
Nguyễn Huy Hoàng
Keyword(s):  
Autosomal Recessive ◽  
Genetic Characterization ◽  
Hydroxylase Deficiency ◽  
Androgen Excess ◽  
Gene Diagnosis ◽  
Autosomal Recessive Disorders ◽  
Classic Form ◽  
21 Hydroxylase Deficiency ◽  
Recessive Disorders

Congenital adrenal hyperplasia (CAH) is a family of autosomal recessive disorders which is characterized by a deficiency of one of the enzymes involved in the synthesis of cortisol from cholesterol by the adrenal cortex. 90% CAH patients respond to 21-hydroxylase deficiency. Less causes include deficiencies of 11β-hydroxylase (11-OH), 17- hydroxylase (17-OH), 3β- hydroxysteroid dehydrogenase (3β- HSD), 20/22 Desmolase etc.. Because of the blocked enzymatic steps, cortisol precursors usually presents with signs of androgen excess which are secreted and cause in masculinization of female external genital, hyponatremia, hyperkalemia and hypovolemia in the classic form due to 21-hydroxylase deficiency. By the early 1950s, it was recognized that in some CAH patients with hypertension develops. This symptom responds to glucorticoid replacement. Most of these patients have an 11β-hydroxylase deficiency. CAH cases arise from 11β-hydroxylase impaired is the second most common form. Mutations in the CYP11B1 gene are the cause of 11β-hydroxylase deficiency. The incident of 11β-hydroxylase deficiency is about 5% to 8% of cases with CAH, in approximately 1/100,000 live birth. Mutations have been detected from different ethnic backgrounds with the highest incidence in group of Morrocan Jews. This article reviews function of enzyme 11β-hydroxylase in cortisol synthesis of andrenal cortex, structure of CYP11B1 gene, diagnosis and treatment of 11β-hydroxylase deficiency and summarised of researching in Wordwild and in Vietnam. Genetic characterization of CYP11B1 genotype has improved our understanding of the phenotype differences in patients. This could be serve as a the basis for genetic counseling and prenatal diagnosis in the future.

scholarly journals The global carrier frequency and genetic prevalence of Upshaw-Schulman syndrome

2021 ◽  
Author(s):  
Ting Zhao ◽  
Shanghua Fan ◽  
Liu Sun
Keyword(s):  
Data Mining ◽  
Allele Frequency ◽  
Thrombotic Microangiopathy ◽  
Carrier Frequency ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Medical Genetics ◽  
Allele Frequencies ◽  
Pathogenic Variants ◽  
Genetics And Genomics

Purpose: Upshaw-Schulman syndrome (USS) is an autosomal recessive disease of thrombotic microangiopathy, caused by pathogenic variants in ADAMTS13. We aimed to (1) perform data mining pathogenicity of ADAMTS13 variants, (2) estimate carrier frequency and genetic prevalence of USS from gnomAD data, and (3) curated ADAMTS13 gene pathogenic variants database. Methods: PubMed and Scopus were comprehensive retrieved. All previously reported pathogenic ADAMTS13 variants were compiled and annotated with gnomAD allele frequencies. Pooled global and population-specific carrier frequency and genetic prevalence for USS were calculated using Hardy-Weinberg equation. Results: we mined reported disease-causing variants, of these were present in gnomAD exomes v2.1.1, filtering by allele frequency, pathogenicity of variants were classified by American College of Medical Genetics and Genomics criteria. The genetic prevalence and carrier frequency of USS was 0.43 per 1 million (95% CI: [0.36, 0.55]) and 1.31 per thousand, respectively. Combining known with novel pathogenic/likely pathogenic variants, the genetic prevalence and carrier frequency are 1 per 1 million (95% CI: [0.89, 1.37]) and 2.1 per thousand, respectively. Conclusion: the genetic prevalence and carrier frequency of Upshaw-Schulman syndrome are within range of previously rough estimated.

scholarly journals The global carrier frequency and genetic prevalence of Upshaw-Schulman syndrome

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Ting Zhao ◽  
Shanghua Fan ◽  
Liu Sun
Keyword(s):  
Allele Frequency ◽  
Carrier Frequency ◽  
Autosomal Recessive ◽  
Autosomal Recessive Disease ◽  
Medical Genetics ◽  
Allele Frequencies ◽  
The Novel ◽  
Thrombotic Microangiopathies ◽  
Pathogenic Variants ◽  
Genetics And Genomics

Abstract Background Upshaw–Schulman syndrome (USS) is an autosomal recessive disease characterized by thrombotic microangiopathies caused by pathogenic variants in ADAMTS13. We aimed to (1) curate the ADAMTS13 gene pathogenic variant dataset and (2) estimate the carrier frequency and genetic prevalence of USS using Genome Aggregation Database (gnomAD) data. Methods Studies were comprehensively retrieved. All previously reported pathogenic ADAMTS13 variants were compiled and annotated with gnomAD allele frequencies. The pooled global and population-specific carrier frequencies and genetic prevalence of USS were calculated using the Hardy-Weinberg equation. Results We mined reported disease-causing variants that were present in the gnomAD v2.1.1, filtered by allele frequency. The pathogenicity of variants was classified according to the American College of Medical Genetics and Genomics criteria. The genetic prevalence and carrier frequency of USS were 0.43 per 1 million (95% CI: [0.36, 0.55]) and 1.31 per 1 thousand population, respectively. When the novel pathogenic/likely pathogenic variants were included, the genetic prevalence and carrier frequency were 1.1 per 1 million (95% CI: [0.89, 1.37]) and 2.1 per 1 thousand population, respectively. Conclusions The genetic prevalence and carrier frequency of USS were within the ranges of previous estimates.

Histopathological and genetic characterization of colorectal mucinous carcinoma

2001 ◽  
Vol 120 (5) ◽  
pp. A166-A166
Author(s):  
S FUJII ◽  
T KUSAKA ◽  
T KAIHARA ◽  
Y UEDA ◽  
T CHIBA ◽  
...  
Keyword(s):  
Genetic Characterization ◽  
Mucinous Carcinoma

Genetic characterization of high hyperdiploidy in childhood acute lymphoblastic leukemia

2009 ◽  
Vol 221 (03) ◽  
Author(s):  
R Vagkopoulou ◽  
C Eckert ◽  
U Ungethüm ◽  
G Körner ◽  
M Stanulla ◽  
...  
Keyword(s):  
Acute Lymphoblastic Leukemia ◽  
Genetic Characterization ◽  
Lymphoblastic Leukemia ◽  
Childhood Acute Lymphoblastic Leukemia
Sign in / Sign up

Export Citation Format

Share Document