scholarly journals Novel Insights into Selected Disease-Causing Mutations within the SLC35A1 Gene Encoding the CMP-Sialic Acid Transporter

2020 ◽  
Vol 22 (1) ◽  
pp. 304
Author(s):  
Bożena Szulc ◽  
Yelyzaveta Zadorozhna ◽  
Mariusz Olczak ◽  
Wojciech Wiertelak ◽  
Dorota Maszczak-Seneczko
Keyword(s):  
Sialic Acid ◽  
Metabolic Diseases ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Congenital Disorders Of Glycosylation ◽  
Gene Encoding ◽  
Structural Assignment ◽  
Microscopic Studies ◽  
Acid Transporter

Congenital disorders of glycosylation (CDG) are a group of rare genetic and metabolic diseases caused by alterations in glycosylation pathways. Five patients bearing CDG-causing mutations in the SLC35A1 gene encoding the CMP-sialic acid transporter (CST) have been reported to date. In this study we examined how specific mutations in the SLC35A1 gene affect the protein’s properties in two previously described SLC35A1-CDG cases: one caused by a substitution (Q101H) and another involving a compound heterozygous mutation (T156R/E196K). The effects of single mutations and the combination of T156R and E196K mutations on the CST’s functionality was examined separately in CST-deficient HEK293T cells. As shown by microscopic studies, none of the CDG-causing mutations affected the protein’s proper localization in the Golgi apparatus. Cellular glycophenotypes were characterized using lectins, structural assignment of N- and O-glycans and analysis of glycolipids. Single Q101H, T156R and E196K mutants were able to partially restore sialylation in CST-deficient cells, and the deleterious effect of a single T156R or E196K mutation on the CST functionality was strongly enhanced upon their combination. We also revealed differences in the ability of CST variants to form dimers. The results of this study improve our understanding of the molecular background of SLC35A1-CDG cases.

scholarly journals A Novel Compound Heterozygous Mutation in ABCB4 Gene Leading to Cholelithiasis, Progressive Familial Intrahepatic Cholestasis (Type 3), and Cirrhosis in a Child

2020 ◽  
Vol 10 (01) ◽  
pp. e134-e136
Author(s):  
Nida Mirza ◽  
Smita Malhotra ◽  
Anupam Sibal
Keyword(s):  
Intrahepatic Cholestasis ◽  
Gall Stone ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Initial Symptom ◽  
Progressive Familial Intrahepatic Cholestasis ◽  
Presenting Symptoms ◽  
Abcb4 Gene ◽  
Type 3

AbstractProgressive familial intrahepatic cholestasis (PFIC) is a heterogeneous group of autosomal recessive disorders of childhood which presents with intermittent or progressive episodes of cholestasis, with jaundice and pruritus as most common presenting symptoms. PFIC type 3 occurs due to mutations in the ABCB4 gene, mutation in this gene has wide spectrum of features which include intrahepatic stones, cholelithiasis, PFIC type 3, and intrahepatic cholestasis of pregnancy. Here, we are reporting a peculiar case of young male adolescent with novel variant compound heterozygote missense mutation in ABCB4 gene who had gall stone as initial symptom, followed by symptoms of PFIC and eventually decompensated chronic liver disease.

scholarly journals Leptin Receptor Compound Heterozygosity in Humans and Animal Models

2021 ◽  
Vol 22 (9) ◽  
pp. 4475
Author(s):  
Claudia Berger ◽  
Nora Klöting
Keyword(s):  
Food Intake ◽  
Animal Models ◽  
Leptin Receptor ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Compound Heterozygosity ◽  
Therapy Options ◽  
Obese Phenotype ◽  
Deficient Mice

Leptin and its receptor are essential for regulating food intake, energy expenditure, glucose homeostasis and fertility. Mutations within leptin or the leptin receptor cause early-onset obesity and hyperphagia, as described in human and animal models. The effect of both heterozygous and homozygous variants is much more investigated than compound heterozygous ones. Recently, we discovered a spontaneous compound heterozygous mutation within the leptin receptor, resulting in a considerably more obese phenotype than described for the homozygous leptin receptor deficient mice. Accordingly, we focus on compound heterozygous mutations of the leptin receptor and their effects on health, as well as possible therapy options in human and animal models in this review.

scholarly journals Novel compound heterozygous mutation in SACS gene leads to a milder autosomal recessive spastic ataxia of Charlevoix‐Saguenay, ARSACS , in a Finnish family

2016 ◽  
Vol 4 (12) ◽  
pp. 1151-1156 ◽  
Author(s):  
Johanna Palmio ◽  
Mikko Kärppä ◽  
Peter Baumann ◽  
Sini Penttilä ◽  
Jukka Moilanen ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Spastic Ataxia

scholarly journals Paediatric Hypophosphatasia in Real-Life Clinical Practise.

Doctor Ru ◽  
2020 ◽  
Vol 19 (10) ◽  
pp. 57-60
Author(s):  
A.V. Vitebskaya ◽  
◽  
Chernova E.V. Chernova ◽  
Keyword(s):  
Alkaline Phosphatase ◽  
Clinical Case ◽  
Clinical Signs ◽  
Real Life ◽  
Compound Heterozygous Mutation ◽  
Heterozygous Mutation ◽  
Compound Heterozygous ◽  
Milk Teeth ◽  
Motor Retardation ◽  
Gait Disturbances

Objective of the Paper: to describe a clinical case of paediatric hypophosphatasia (HPP) and identify clinical signs, most characteristic of the paediatric HPP form. Key Points. HPP is an congenital rickets-like disease caused by reduced activity of tissue-nonspecific alkaline phosphatase (ALP). According to the time of manifestation, there are perinatal, infant, paediatric, and adult HPPs. The article describes a clinical case of paediatric HPP in a 3.5-year old boy. HPP was diagnosed due to reduced ALP and characteristic X-ray findings. The diagnosis was confirmed with DNA testing: compound heterozygous mutation in с.571 G>A/с.144_148dup of ALPL was found. Conclusion. Typical findings in paediatric HPP are growth retardation and muscular hypotonia, motor retardation; gait disturbances, myalgia, marked fatigue causing limited period of walking; rachitic deformations, premature loss of milk teeth with unchanged roots, respiratory disturbances, and frequent bronchopulmonary disorders. Keywords: hypophosphatasia, children, alkaline phosphatase.

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