Congenital Disorders
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2021 ◽  
Giovanna L. Gallo ◽  
Ayelen Valko ◽  
Nathalia Herrera Aguilar ◽  
Ariel D. Weisz ◽  
Cecilia D'Alessio

Congenital Disorders of Glycosylation Type I (CDG-I) are inherited human diseases caused by deficiencies in lipid-linked oligosaccharide (LLO) synthesis or the glycan transfer to proteins during N-glycosylation. We constructed a platform of 16 Schizosaccharomyces pombe mutant strains that synthesize all possible theoretical combinations of LLOs containing three to zero Glc and nine to five Man. The occurrence of unexpected LLOs suggested the requirement of specific Man residues for glucosyltransferases activities. We then quantified protein hypoglycosylation in each strain and found that in S. pombe the presence of Glc in the LLO is more relevant to the transfer efficiency than the amount of Man residues. Surprisingly, a decrease in the number of Man in glycans somehow improved the glycan transfer. The most severe hypoglycosylation was produced in cells completely lacking Glc and having a high number of Man. This deficiency could be reverted by expressing a single subunit OST with a broad range of substrate specificity. Our work shows the usefulness of this new S. pombe set of mutants as a platform to model the molecular bases of human CDG-I diseases.

2021 ◽  
Vol 23 (5) ◽  
pp. 441-444
Zhanna I. Glinkina ◽  
Elena V. Kulakova ◽  
Elena G. Lebedeva ◽  
Varvara S. Kuzmicheva ◽  
Nataliya P. Makarova

The frequency of structural chromosomal transpositions can range from 1.8 to 8% among patients with reproductive disorders. There are several types of the rarest chromosomal abnormalities: insertion (insertion of a chromosomal region) and inversion (rotation of a chromosome region). This article describes a clinical case of the infertility treatment using assisted reproductive technologies in a woman with a rare chromosomal abnormality: simultaneous insertion and inversion of chromosomes 46, XX, ins (13;4)(q34;p14p15.3), inv(4)(p14q12). The structure and frequency of chromosomal aberrations were determined by high-throughput sequencing in preimplantation embryos. The result of the sequencing analysis showed that unbalanced variants for a known pathology were detected in 9 (56.3%) out of 16 observations, while in 6 (37%) only for a pathology known in the karyotype and in 3 (19%) they were presented simultaneously with the pathology of other chromosomes or with mosaicism. According to the results of the study, in preimplantation embryos, where one of the parents had chromosomal abnormalities, in addition to unbalanced variants, there is aneuploidy of other chromosomes not involved in the known pathology. They are described in 3 (21%) out of 14 observations of all identified pathology. In this regard, patients with aberrations in the karyotype are recommended, whenever possible, to carry out preimplantation genetic testing of structural rearrangements by methods allowed to analyze all chromosomes simultaneously. For example, high-throughput sequencing on the Illumina platform may become an alternative for prenatal diagnostics, which is performed in fertile couples with high risk of having a child with hereditary or congenital disorders. In the case of detection of chromosomal changes in the fetus, patients are faced with a number of ethical issues related to the necessity for medical abortion, which may contradict their religious and moral convictions.

Uro ◽  
2021 ◽  
Vol 1 (4) ◽  
pp. 238-244
Georgios Zervopoulos ◽  
Filippos Venetsanos

Urolithiasis is a common condition, and it represents a large number of hospital visits. Under the term infundibulopelvic dysgenesis, many conditions amongst a spectrum of congenital disorders of the pelvicalyceal system are described. Retrograde intrarenal surgery (RIRS) is an effective and safe treatment modality in the management of urinary system stone disease. Fluoroscopic imaging is a cornerstone in endourology. Herein, we present a case where we diagnosed an obstructed calyx during RIRS for renal calculi and operated on it. In this extraordinary case, contrast agent was trapped in the calyx mimicking a renal stone and that was the reason that we discovered the infundibular stenosis. The patient, 24 h after the operation, left the hospital without any complications reported.

Cells ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 3275
Zinia D’Souza ◽  
Farhana Taher Sumya ◽  
Amrita Khakurel ◽  
Vladimir Lupashin

The Golgi is the central organelle of the secretory pathway and it houses the majority of the glycosylation machinery, which includes glycosylation enzymes and sugar transporters. Correct compartmentalization of the glycosylation machinery is achieved by retrograde vesicular trafficking as the secretory cargo moves forward by cisternal maturation. The vesicular trafficking machinery which includes vesicular coats, small GTPases, tethers and SNAREs, play a major role in coordinating the Golgi trafficking thereby achieving Golgi homeostasis. Glycosylation is a template-independent process, so its fidelity heavily relies on appropriate localization of the glycosylation machinery and Golgi homeostasis. Mutations in the glycosylation enzymes, sugar transporters, Golgi ion channels and several vesicle tethering factors cause congenital disorders of glycosylation (CDG) which encompass a group of multisystem disorders with varying severities. Here, we focus on the Golgi vesicle tethering and fusion machinery, namely, multisubunit tethering complexes and SNAREs and their role in Golgi trafficking and glycosylation. This review is a comprehensive summary of all the identified CDG causing mutations of the Golgi trafficking machinery in humans.

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3117
Nobuhiko Okamoto ◽  
Tatsuyuki Ohto ◽  
Takashi Enokizono ◽  
Yoshinao Wada ◽  
Tomohiro Kohmoto ◽  

Congenital disorders of glycosylation (CDG), inherited metabolic diseases caused by defects in glycosylation, are characterized by a high frequency of intellectual disability (ID) and various clinical manifestations. Two siblings with ID, dysmorphic features, and epilepsy were examined using mass spectrometry of serum transferrin, which revealed a CDG type 2 pattern. Whole-exome sequencing showed that both patients were homozygous for a novel pathogenic variant of MAN1B1 (NM_016219.4:c.1837del) inherited from their healthy parents. We conducted a HPLC analysis of sialylated N-linked glycans released from total plasma proteins and characterized the α1,2-mannosidase I activity of the lymphocyte microsome fraction. The accumulation of monosialoglycans was observed in MAN1B1-deficient patients, indicating N-glycan-processing defects. The enzymatic activity of MAN1B1 was compromised in patient-derived lymphocytes. The present patients exhibited unique manifestations including early-onset epileptic encephalopathy and cerebral infarction. They also showed coagulation abnormalities and hypertransaminasemia. Neither sibling had truncal obesity, which is one of the characteristic features of MAN1B1-CDG.

2021 ◽  
Vol 1 (4) ◽  
pp. 131-143
Edris Queiroz Lopes ◽  
Tais Elena Caneloi ◽  
Tatiane Gonçalves De Lima ◽  
Drielly Stefany Queiroz de Lucca

Connatural alterations can be deformations or malformations discovered in the embryonic development phase of the animal, which can disguise structures or roles of the systems. Congenital disorders can range from small changes, slight changes, serious adulterations and also genetic inconsistencies. There are no apparent defined reasons, and these changes may be caused by environmental and genetic factors. Pigopagus twins are joined at the back, have a coccyx, the gastrointestinal tract may have a single or separate rectum, a single bladder in some cases and obligatorily separate spinal cord and always with sharing of the pelvic bones. The ischiopagus are united by the ventral region from the navel to the pelvis, two sacrum and two pubic symphysis, in addition to a single gastrointestinal tract and a varied number of limbs. Reporting and discussing the morphological and anatomical deformities presented in a species of Squalus acanthias, recorded by LOPES in 2020, is a big step to better understand the anatomy and physiology of animals, which are considered the top of the food chain in the oceans and are in serious trouble. risk of extinction. RESUMO Alterações conaturais podem ser deformações ou más-formações descobertas na fase de desenvolvimento embrionário do animal, podendo disfarçar estruturas ou papéis dos sistemas. Os distúrbios congênitos podem ocorrer desde pequenas mudanças, alterações leves, adulterações sérias e também incoerências genéticas. Não existem motivos aparentes definidos, podendo estas alterações serem causados por fatores ambientais e genéticos. Os gêmeos Pigopagus são unidos pelo dorso, apresentam um coccix, o trato gastrointestinal pode apresentar reto único ou separado, bexiga única em alguns casos e obrigatoriamente medula espinhal separada e sempre com compartilhamento dos ossos pélvicos. Os isquiópagos apresentam-se unidos pela região ventral do umbigo à pelve, dois sacros e duas sínfises púpicas além de tratos gastrointestinal único e número de membros variados. Relatar e discutir as deformidades morfológicas e anatômicas apresentadas em uma especie de Squalus acanthias, registrada por LOPES em 2020, é um grande passo para entender melhor a anatomia e fisiologia de animais, que são considerados o topo da cadeia alimentar nos oceanos e correm um sério risco de extinção.  

2021 ◽  
Hannes E Bülow ◽  
Maisha Rahman ◽  
Nelson J. Ramirez-Suarez ◽  
Carlos A Diaz-Balzac

N-glycans are molecularly diverse sugars borne by over 70% of proteins transiting the secretory pathway and have been implicated in protein folding, stability, and localization. Mutations in genes important for N-glycosylation result in congenital disorders of glycosylation that are often associated with intellectual disability. Here, we show that structurally distinct N-glycans regulate the activity of an extracellular protein complex involved in patterning of somatosensory dendrites in Caenorhabditis elegans. Specifically, aman-2/Golgi alpha-mannosidase II, a conserved key enzyme in the biosynthesis of specific N-glycans regulates the activity of the Menorin adhesion complex without obviously affecting protein stability and localization of its components. AMAN-2 functions cell-autonomously to ensure decoration of the neuronal transmembrane receptor DMA-1/LRR-TM with high-mannose/hybrid N-glycans. Moreover, distinct types of N-glycans on specific N-glycosylation sites regulate the DMA-1/LRR-TM receptor, which together with three other extracellular proteins forms the Menorin adhesion complex. In summary, specific N-glycan structures regulate dendrite patterning by coordinating the activity of an extracellular adhesion complex suggesting that the molecular diversity of N-glycans can contribute to developmental specificity in the nervous system.

2021 ◽  
Vol 14 (1) ◽  
Chunyan Chen ◽  
Jiong Gao ◽  
Qing Lv ◽  
Chen Xu ◽  
Yu Xia ◽  

Abstract Background Joubert syndrome (JS) is a group of rare congenital disorders characterized by cerebellar vermis dysplasia, developmental delay, and retina dysfunctions. Herein, we reported a Chinese patient carrying a new variant in the AHI1 gene with mild JS, and the 3D structure of the affected Jouberin protein was also predicted. Case presentation The patient was a 31-year-old male, who presented difficulty at finding toys at the age of 2 years, night blindness from age of 5 years, intention tremor and walking imbalance from 29 years of age. Tubular visual field and retina pigmentation were observed on ophthalmology examinations, as well as molar tooth sign on brain magnetic resonance imaging (MRI). Whole exome sequence revealed two compound heterozygous variants at c.2105C>T (p.T702M) and c.1330A>T (p.I444F) in AHI1 gene. The latter one was a novel mutation. The 3D protein structure was predicted using I-TASSER and PyMOL, showing structural changes from functional β-sheet and α-helix to non-functional D-loop, respectively. Conclusions Mild JS due to novel variants at T702M and I444F in the AHI1 gene was reported. The 3D-structural changes in Jouberin protein might underlie the pathogenesis of JS.

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