scholarly journals A Novel Homozygous ALG12 Mutation in a Patient with CDG Type Ig: New Report of a Case with a Mild Phenotype

2021 ◽  
pp. 1-6
Author(s):  
Antonio Gennaro Nicotera ◽  
Giulia Spoto ◽  
Francesco Calì ◽  
Giusi Romeo ◽  
Antonino Musumeci ◽  
...  
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Genetic Diseases ◽  
Failure To Thrive ◽  
Congenital Disorders ◽  
Homozygous Mutation ◽  
Congenital Disorders Of Glycosylation ◽  
Mild Phenotype ◽  
Dysmorphic Features ◽  
Rare Genetic Diseases

Congenital disorders of glycosylation (CDG) are a group of rare genetic diseases caused by the deficiency of enzymes involved in the biosynthesis or remodeling of the glycan moieties of glycoconjugates. Most of CDG are autosomal recessive; however, few of them show autosomal dominant or X-linked inheritance. ALG12-CDG is an autosomal recessive inherited defect caused by a deficiency in the α-mannosyltransferase, dolichyl-P-mannose: Man7-GlcNAc-2-PP-dolichyl-alpha-6-mannosyltransferase (mannosyltransferase 8), which determines Man7GlcNAc2-PP-dolichol accumulation in tissues including fibroblasts. The clinical features of ALG12-CDG include dysmorphic features, developmental delay, hypotonia, progressive microcephaly, hypogammaglobulinemia, coagulopathies, and failure to thrive. Herein, we describe the case of a Sicilian patient with a milder phenotype bearing an <i>ALG12</i> homozygous mutation. To date, including this patient, only 16 cases have been described with this form of CDG. Furthermore, our study contributes to understanding the milder ALG12-CDG cases and to further expanding the genotype-phenotype spectrum.

scholarly journals Platelets and Defective N-Glycosylation

2020 ◽  
Vol 21 (16) ◽  
pp. 5630 ◽  
Author(s):  
Elmina Mammadova-Bach ◽  
Jaak Jaeken ◽  
Thomas Gudermann ◽  
Attila Braun
Keyword(s):  
Endoplasmic Reticulum ◽  
Thermodynamic Stability ◽  
Metabolic Pathways ◽  
Genetic Diseases ◽  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Abnormal Protein ◽  
Rare Genetic Diseases ◽  
Covalently Linked ◽  
Asparagine Residue

N-glycans are covalently linked to an asparagine residue in a simple acceptor sequence of proteins, called a sequon. This modification is important for protein folding, enhancing thermodynamic stability, and decreasing abnormal protein aggregation within the endoplasmic reticulum (ER), for the lifetime and for the subcellular localization of proteins besides other functions. Hypoglycosylation is the hallmark of a group of rare genetic diseases called congenital disorders of glycosylation (CDG). These diseases are due to defects in glycan synthesis, processing, and attachment to proteins and lipids, thereby modifying signaling functions and metabolic pathways. Defects in N-glycosylation and O-glycosylation constitute the largest CDG groups. Clotting and anticlotting factor defects as well as a tendency to thrombosis or bleeding have been described in CDG patients. However, N-glycosylation of platelet proteins has been poorly investigated in CDG. In this review, we highlight normal and deficient N-glycosylation of platelet-derived molecules and discuss the involvement of platelets in the congenital disorders of N-glycosylation.

Characteristic dysmorphic features in congenital disorders of glycosylation type IIb

2017 ◽  
Vol 63 (3) ◽  
pp. 383-386 ◽  
Author(s):  
Yoon-Myung Kim ◽  
Go Hun Seo ◽  
Euiseok Jung ◽  
Ja-Hyun Jang ◽  
Sook Za Kim ◽  
...  
Keyword(s):  
Congenital Disorders ◽  
Congenital Disorders Of Glycosylation ◽  
Dysmorphic Features

scholarly journals Autosomal Recessive Oculodentodigital Dysplasia: A Case Report and Review of the Literature

2018 ◽  
Vol 154 (4) ◽  
pp. 181-186 ◽  
Author(s):  
Elifcan Taşdelen ◽  
Ceren D. Durmaz ◽  
Halil G. Karabulut
Keyword(s):  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Stop Codon ◽  
Premature Stop Codon ◽  
Rare Condition ◽  
Clinical Findings ◽  
Homozygous Mutation ◽  
Nasal Bridge ◽  
Oculodentodigital Dysplasia ◽  
Autosomal Recessive Manner

Oculodentodigital dysplasia (ODDD) is a rare condition characterized by a typical facial appearance and variable findings of the eyes, teeth, and fingers. ODDD is caused by mutations in the GJA1 gene in chromosome 6q22 and inherited in an autosomal dominant manner in the majority of the patients. However, in recent clinical reports, autosomal recessive ODDD cases due to by GJA1 mutations were also described. Here, we report on a 14-year-old boy with microphthalmia, microcornea, narrow nasal bridge, hypoplastic alae nasi, prominent columnella, hypodontia, dental caries, and partial syndactyly of the 2nd and 3rd toes. These clinical findings were concordant with the diagnosis of ODDD, and a novel homozygous mutation (c.442C>T, p.Arg148Ter) was determined in the GJA1 gene leading to a premature stop codon. His phenotypically normal parents were found to be carriers of the same mutation. This is the third family in the literature in which ODDD segregates in an autosomal recessive manner.

scholarly journals Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up

2020 ◽  
Author(s):  
Anna Bogdańska ◽  
Patryk Lipiński ◽  
Paulina Szymańska-Rożek ◽  
Aleksandra Jezela-Stanek ◽  
Dariusz Rokicki ◽  
...  
Keyword(s):  
Failure To Thrive ◽  
Congenital Disorders ◽  
Type I ◽  
Congenital Disorders Of Glycosylation ◽  
Diagnostic Features ◽  
Strong Negative Correlation ◽  
Single Centre Study ◽  
Long Term Follow Up

Abstract Background: Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and the attachment of glycans to proteins and lipids. Our study aimed to describe the clinical, biochemical and molecular findings of CDG patients, and to present the long-term follow-up. Material and methods: A single-centre study (1995-2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation, diagnosed based on the serum transferrin (Tf) and apolipoprotein C-III (apoC-III) isoforms analysis, and confirmed molecularly, was performed. Results: Among 32 patients included into the study, 24 had type I Tf isoform profile, in 12 of them deficient PMM2 activity was detected. Three patients were diagnosed with ALG13-CDG; serum Tf isoform profile was normal in one of them, in one other was indicative for type I. Four patients had type II Tf isoform profile. The phenotypic and genotypic spectrum of 32 patients with CDG during long-term (in some cases over 20 years) observation was characterised and several measurements of serum Tf isoforms taken. Statistical analysis revealed strong negative correlation between Asialo-Tf and Tetrasialo-Tf, as well as between Disialo-Tf and Tetrasialo-Tf. Positive correlation was shown between Tetrasialo-Tf and Penasialo-Tf. Within type I CDG, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in the such diagnostic features as: cerebellar ataxia, failure to thrive, hypothyroidism, pericardial effusion, cardiomyopathy, inverted nipples, prolonged INR. The effect of treatment with mannose in 2 patients with MPI-CDG were assesed and we found that % of Asialo-Tf, Monosialo-Tf, and Disialo-Tf was significanty lowered, whereas Tetrasialo- Tf and Pentasialo-Tf rose, coming closer or falling into the reference range. Conclusions: The novel finding was an abnormal Tf IEF pattern in two ALG13-CDG patients and normal in one ALG1-CDG patient. Clinical manifestation of presented CDG patients was similar to that reported in the literature. Mannose supplementation in MPI-CDG patients, as well as galactose supplementation in PGM-CDG patient improved patients’ clinical picture and Tf isoform profiles.

scholarly journals A Novel Frameshift Homozygous Mutation in DHCR7 with a Known Missense Homozygous Mutation in the PROC in a 6-Year-Old Boy: A Child with Two Rare Genetic Diseases

2019 ◽  
Vol 08 (03) ◽  
pp. 168-171
Author(s):  
Evren Gumus
Keyword(s):  
Genetic Disorders ◽  
Genetic Diseases ◽  
Laboratory Data ◽  
Valuable Insight ◽  
Homozygous Mutation ◽  
Homozygous Variant ◽  
Whole Exome ◽  
Rare Genetic Diseases ◽  
Proc Gene ◽  
Autosomal Recessive Diseases

AbstractIn the present case report, we described a 6-year-old-boy with developmental delay, mental retardation, lack of speech, skin scars, and 2 to 3 toe syndactyly from healthy consanguineous Turkish parents. The whole exome sequencing (WES) analysis of this patient showed homozygous variant c.418T > C p.(Cys140Arg) in PROC gene and novel homozygous variant c.57dupC p.(Asn20Glnfs*2) in the DHCR7 gene. This finding demonstrated that WES is of great value for the diagnosis of two separate genetic disorders in a patient with multiple dysmorphic and other clinical features. It should also be kept in mind that the coexistence of two autosomal recessive diseases could be observed in highly related consanguineous marriages. The combined evaluation of clinical and laboratory data provided extremely valuable insight into the diagnosis of this unique case.

scholarly journals Prevalence of Congenital Disorders of Glycosylation in Childhood Epilepsy and Effects of Anti-Epileptic Drugs on the Transferrin Isoelectric Focusing Test

Genes ◽  
2021 ◽  
Vol 12 (8) ◽  
pp. 1227
Author(s):  
Grace Silver ◽  
Shalini Bahl ◽  
Dawn Cordeiro ◽  
Abhinav Thakral ◽  
Taryn Athey ◽  
...  
Keyword(s):  
Isoelectric Focusing ◽  
Statistical Tests ◽  
Genetic Diseases ◽  
Cost Effective ◽  
Congenital Disorders ◽  
Childhood Epilepsy ◽  
Congenital Disorders Of Glycosylation ◽  
Exact Test ◽  
Liver Functions ◽  
Effective Diagnosis

Introduction: Childhood epilepsy is one of the most common neurological problems. The transferrin isoelectric focusing (TIEF) test is a screening test for congenital disorders of glycosylation (CDG). We identified abnormal TIEF test in children with epilepsy in our epilepsy genetics clinic. To determine if an abnormal TIEF test is associated with anti-epileptic medications or abnormal liver functions, we performed a retrospective cohort study. Methods: This study was performed between January 2012 and March 2020. Electronic patient charts were reviewed. Standard non-parametric statistical tests were applied using R statistical software. Fischer’s exact test was used for comparisons. Results: There were 206 patients. The TIEF test was abnormal in 11% (23 out of 206) of the patients. Nine patients were diagnosed with CDG: PMM2-CDG (n = 5), ALG3-CDG (n = 1), ALG11-CDG (n = 2), SLC35A2-CDG (n = 1). We report 51 different genetic diseases in 84 patients. Two groups, (1) abnormal TIEF test; (2) normal TIEF test, showed statistically significant differences for abnormal liver functions and for valproic acid treatment. Conclusion: The TIEF test guided CDG diagnosis in 2.9% of the patients. Due to the high prevalence of CDG (4.4%) in childhood epilepsy, the TIEF test might be included into the diagnostic investigations to allow earlier and cost-effective diagnosis.

scholarly journals Clinical, biochemical and molecular phenotype of congenital disorders of glycosylation: long-term follow-up

2021 ◽  
Vol 16 (1) ◽  
Author(s):  
Anna Bogdańska ◽  
Patryk Lipiński ◽  
Paulina Szymańska-Rożek ◽  
Aleksandra Jezela-Stanek ◽  
Dariusz Rokicki ◽  
...  
Keyword(s):  
Failure To Thrive ◽  
Congenital Disorders ◽  
Type I ◽  
Congenital Disorders Of Glycosylation ◽  
Diagnostic Features ◽  
Strong Negative Correlation ◽  
Single Center Study ◽  
Long Term Follow Up

Abstract Background Congenital disorders of glycosylation (CDG) result from defects in the synthesis of glycans and the attachment of glycans to proteins and lipids. Our study aimed to describe the clinical, biochemical, and molecular findings of CDG patients, and to present the long-term follow-up. Material and methods A single-center study (1995–2019 years) of patients with congenital disorders of N-glycosylation and combined N- and O-hypoglycosylation was performed. Results Among 32 patients included into the study, there were 12 PMM2-CDG, 3 ALG13-CDG, 3 ALG1-CDG, 1 ALG3-CDG, 3 MPI-CDG, 1 PGM1-CDG, 4 SRD5A3-CDG, 1 DPAGT1-CDG, 3 ATP6AP1-CDG, 1 ATP6V0A2-CDG. The phenotypic and genotypic spectrum during long-term (in some cases over 20 years) observation was characterised and several measurements of serum Tf isoforms taken. Statistical analysis revealed strong negative correlation between asialo-Tf and tetrasialo-Tf, as well as between disialo-Tf and tetrasialo-Tf. Within CDG type I, no difference in % Tf isoforms was revealed between PMM2-CDG and non-PMM2-CDG patients. However, these two groups differed significantly in such diagnostic features as: cerebellar ataxia, failure to thrive, hypothyroidism, pericardial effusion, cardiomyopathy, inverted nipples, prolonged INR. The effect of treatment with mannose in 2 patients with MPI-CDG was assessed and we found that % of asialo-Tf, monosialo-Tf, and disialo-Tf was significantly lowered, whereas tetrasialo-Tf and pentasialo-Tf rose, coming closer or falling into the reference range. Conclusions The novel finding was an abnormal Tf IEF pattern in two ALG13-CDG patients and normal in one ALG1-CDG patient. Clinical manifestation of presented CDG patients was similar to that reported in the literature. Mannose supplementation in MPI-CDG patients, as well as galactose supplementation in PGM1-CDG patient, improved patients’ clinical picture and Tf isoform profiles.

Can progression of autosomal dominant or autosomal recessive polycystic kidney disease be prevented?

2001 ◽  
Vol 21 (5) ◽  
pp. 430-440 ◽  
Author(s):  
Ira D. Davis ◽  
Katherine MacRae Dell ◽  
William E. Sweeney ◽  
Ellis D. Avner
Keyword(s):  
Kidney Disease ◽  
Polycystic Kidney Disease ◽  
Autosomal Recessive ◽  
Autosomal Dominant ◽  
Polycystic Kidney

A Case of Congenital Glucose Galactose Malabsorption with a New Mutation in the SLC5A1 Gene

2020 ◽  
Author(s):  
Hasan Akduman ◽  
Dilek Dilli ◽  
Serdar Ceylaner
Keyword(s):  
Mutation Analysis ◽  
Autosomal Recessive ◽  
Glucose Transporter ◽  
Neonatal Period ◽  
Autosomal Recessive Disorder ◽  
Homozygous Mutation ◽  
New Mutation ◽  
Early Neonatal Period ◽  
Sodium Dependent ◽  
Hypernatremic Dehydration

AbstractCongenital glucose-galactose malabsorption (CGGM) is an autosomal recessive disorder originating from an abnormal transporter mechanism in the intestines. It was sourced from a mutation in the SLC5A1 gene, which encodes a sodium-dependent glucose transporter. Here we report a 2-day-old girl with CGGM who presented with severe hypernatremic dehydration due to diarrhea beginning in the first hours of life. Mutation analysis revealed a novel homozygous mutation NM_000343.3 c.127G > A (p.Gly43Arg) in the SLC5A1 gene. Since CGGM can cause fatal diarrhea in the early neonatal period, timely diagnosis of the disease seems to be essential.

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