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Zhonghua Er Ke Za Zhi = Chinese Journal... Dec 2019To investigate the clinical and genetic characteristics of 3 patients with mucolipidosis and to perform literature review. A retrospective analysis was made on the... (Review)
Review
To investigate the clinical and genetic characteristics of 3 patients with mucolipidosis and to perform literature review. A retrospective analysis was made on the clinical data and genetic test results of 3 pedigrees with mucolipidosis. The patients were followed up at the Genetic and Prenatal Diagnosis Center of the First Affiliated Hospital of Zhengzhou University from February 2016 to August 2018. A neonatal inherited metabolic diseases gene panel including GNPTAB, GNPTG, MCOLN1, etc. was used for next-generation sequencing (NGS) based testing. Sanger sequencing was subsequently used to confirm the suspected pathological variants in the patients and their family members. Original papers on mucolipidosis published up to December 2018 were retrieved from PubMed, CNKI and WanFang databases by using the key words "mucolipidosis" AND "Chinese" . The onset ages ranged from (9-90) days. The common clinical characteristics of the 3 patients are developmental delay and skeletal abnormalities. Targeted NGS revealed 5 different variations all in GNPTAB including p.Arg364Ter, p.Ser385Leu, p.Try404Ter, p. Arg587Ter, c.1284+1G>T. Two variants p.Ser385Leu and c.1284+1G>T were novel. Twenty-six cases of mucolipidosis have been reported in Chinese from 8 papers, which included 11 type ML Ⅱα/β, 11 type ML Ⅲ α/β and 4 type ML Ⅲ γ. c.2715+1G>A and p.Arg364Ter variants are likely the hot variants in Chinese ML patients. Mucolipidosis is a rare autosomal recessive disorder characterized by developmental delay and skeletal abnormalities. NGS plus Sanger sequencing detection is effective and accurate for making genetic diagnosis. p.Ser385Leu and c.1284+1G>T of GNPTAB gene are identified as novel pathogenic variants. GNPTAB gene is the main disease causing gene among Chinese ML patients, and c.2715+1G>A and p.Arg364Ter are the most common variants.
Topics: Female; Genetic Testing; Humans; Infant; Infant, Newborn; Mucolipidoses; Mutation; Pedigree; Pregnancy; Retrospective Studies; Transferases (Other Substituted Phosphate Groups)
PubMed: 31795562
DOI: 10.3760/cma.j.issn.0578-1310.2019.12.010 -
American Journal of Medical Genetics.... Jul 2019Mucolipidosis (ML) is a rare lysosomal storage disorder with a wide spectrum of disease severity according to the type. Sleep-disordered breathing is recognized as a...
Mucolipidosis (ML) is a rare lysosomal storage disorder with a wide spectrum of disease severity according to the type. Sleep-disordered breathing is recognized as a characteristic feature of ML but objective data are scarce. The aim of the study was to describe sleep data and medical management in children with ML α/β. All patients with ML α/β followed at a national reference center of ML were included. Five patients had ML II, one patient had ML III and one patient had ML II-III. One patient was started on noninvasive ventilation (NIV) to allow extubation after prolonged invasive mechanical ventilation. The six other patients underwent sleep study at a median age of 1.8 years (range 4 months-17.4 years). Obstructive sleep apnea (OSA) was observed in all patients with a median apnea-hypopnea index (AHI) of 36 events/hr (range 5-52) requiring continuous positive airway pressure (CPAP) or NIV. CPAP/NIV resulted in an improvement of nocturnal gas exchange and was continued in all patients with an excellent compliance. Two patients died. Systematic sleep studies are recommended at time of diagnosis in ML. CPAP or NIV are effective treatments of OSA, well tolerated, and may contribute to improve the quality of life of patients and caregivers.
Topics: Adolescent; Child; Child, Preschool; Continuous Positive Airway Pressure; Disease Management; Female; Gene Expression; Humans; Infant; Male; Mucolipidoses; Mutation; Noninvasive Ventilation; Patient Compliance; Polysomnography; Quality of Life; Severity of Illness Index; Sleep Apnea, Obstructive; Transferases (Other Substituted Phosphate Groups); Treatment Outcome
PubMed: 31038846
DOI: 10.1002/ajmg.a.61167 -
Journal of Midwifery & Women's Health 2004Mucolipidosis type IV (MLIV) is a rare genetic disorder that primarily affects persons of Ashkenazi Jewish descent. Current information available about testing options... (Review)
Review
Mucolipidosis type IV (MLIV) is a rare genetic disorder that primarily affects persons of Ashkenazi Jewish descent. Current information available about testing options and the Ashkenazi Jewish Screening panel, including the addition of screening for MLIV, is presented. The importance of genetic screening and counseling is emphasized.
Topics: Founder Effect; Gene Frequency; Genetic Predisposition to Disease; Genetic Testing; Humans; Jews; Mucolipidoses; New York City; United States
PubMed: 15236718
DOI: 10.1016/j.jmwh.2004.04.009 -
Biochemical Society Transactions Dec 2010MLIV (mucolipidosis type IV) is a neurodegenerative lysosomal storage disorder caused by mutations in MCOLN1, a gene that encodes TRPML1 (mucolipin-1), a member of the...
MLIV (mucolipidosis type IV) is a neurodegenerative lysosomal storage disorder caused by mutations in MCOLN1, a gene that encodes TRPML1 (mucolipin-1), a member of the TRPML (transient receptor potential mucolipin) cation channels. Two additional homologues are TRPML2 and TRPML3 comprising the TRPML subgroup in the TRP superfamily. The three proteins play apparently key roles along the endocytosis process, and thus their cellular localization varies among the different group members. Thus TRPML1 is localized exclusively to late endosomes and lysosomes, TRPML2 is primarily located in the recycling clathrin-independent GPI (glycosylphosphatidylinositol)-anchored proteins and early endosomes, and TRPML3 is primarily located in early endosomes. Apparently, all three proteins' main physiological function underlies Ca(2+) channelling, regulating the endocytosis process. Recent findings also indicate that the three TRPML proteins form heteromeric complexes at least in some of their cellular content. The physiological role of these complexes in lysosomal function remains to be elucidated, as well as their effect on the pathophysiology of MLIV. Another open question is whether any one of the TRPMLs bears additional function in channel activity.
Topics: Humans; Mucolipidoses; Mutation; Protein Isoforms; TRPM Cation Channels
PubMed: 21118102
DOI: 10.1042/BST0381432 -
Pflugers Archiv : European Journal of... Oct 2005Mucolipidosis type IV (MLIV) is a rare, neurogenetic disorder characterized by developmental abnormalities of the brain, and impaired neurological, ophthalmological, and... (Review)
Review
Mucolipidosis type IV (MLIV) is a rare, neurogenetic disorder characterized by developmental abnormalities of the brain, and impaired neurological, ophthalmological, and gastric function. Considered a lysosomal disease, MLIV is characterized by the accumulation of large vacuoles in various cell types. Recent evidence indicates that MLIV is caused by mutations in MCOLN1, the gene that encodes mucolipin-1 (ML1), a 65-kDa protein showing sequence homology and topological similarities with polycystin-2 and other transient receptor potential (TRP) channels. In this report, our observations on the channel properties of ML1, and molecular pathophysiology of MLIV are reviewed and expanded. Our studies have shown that ML1 is a multiple sub-conductance, non-selective cation channel. MLIV-causing mutations result in functional differences in the channel protein. In particular, the V446L and DeltaF408 mutations retain channel function but have interesting functional differences with regards to pH dependence and Ca(2+) transport. While the wild-type protein is inhibited by Ca(2+) transport, mutant ML1 is not. Atomic force microscopy imaging of ML1 channels shows that changes in pH modify the aggregation and size of the ML1 channels, which has an impact on vesicular fusogenesis. The new evidence provides support for a novel role of ML1 cation channels in vesicular acidification and normal endosomal function.
Topics: Amino Acid Sequence; Calcium; Humans; Hydrogen-Ion Concentration; Microscopy, Atomic Force; Molecular Sequence Data; Mucolipidoses; Sequence Alignment; TRPM Cation Channels; Transient Receptor Potential Channels
PubMed: 16133264
DOI: 10.1007/s00424-005-1448-9 -
Cardiology in the Young May 2021Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with... (Review)
Review
Sialidosis, a rare autosomal recessive disorder, is caused by a deficiency of NEU1 encoded enzyme alpha-N-acetyl neuraminidase. We report a premature male with neonatal-onset type II sialidosis which was associated with left ventricular dysfunction. The clinical presentation and subsequent progression which culminated in his untimely death at 16 months of age are succinctly described. Early-onset cardiovascular involvement as noted in this patient is not well characterised. The case report is supplemented by a comprehensive review of the determinants, characteristics, and the clinical course of cardiovascular involvement in this rare condition.
Topics: Humans; Infant, Newborn; Male; Mucolipidoses; Neuraminidase; Syndrome
PubMed: 33507140
DOI: 10.1017/S1047951120004953 -
Neurology Jun 2014To identify the genetic cause of a familial form of late-onset action myoclonus in 2 unrelated patients. Both probands had 2 siblings displaying a similar disorder.... (Review)
Review
OBJECTIVE
To identify the genetic cause of a familial form of late-onset action myoclonus in 2 unrelated patients. Both probands had 2 siblings displaying a similar disorder. Extensive laboratory examinations, including biochemical assessment for urine sialic acid in the 2 probands, were negative.
METHODS
Exome sequencing was performed in the probands using an Illumina platform. Segregation analysis of putative mutations was performed in all family members by standard Sanger sequencing protocols.
RESULTS
NEU1 mutations were detected in 3 siblings of each family with prominent cortical myoclonus presenting in the third decade of life and having a mild and slowly progressive course. They did not have macular cherry-red spot and their urinary sialic acid excretion was within normal values. Genetic analysis demonstrated a homozygous mutation in family 1 (c.200G>T, p.S67I) and 2 compound heterozygous mutations in family 2 (c.679G>A, p.G227R; c.913C>T, p.R305C).
CONCLUSIONS
Our observation indicates that sialidosis should be suspected and the NEU1 gene analyzed in patients with isolated action myoclonus presenting in adulthood in the absence of other typical clinical and laboratory findings.
Topics: Adult; Age of Onset; Diagnosis, Differential; Exome; Female; Genome-Wide Association Study; Humans; Male; Mucolipidoses; Mutation; Myoclonus; Neuraminidase; Pedigree
PubMed: 24808020
DOI: 10.1212/WNL.0000000000000482 -
Cells Feb 2022Mucolipidosis IV (MLIV) is an autosomal recessive pediatric disease that leads to motor and cognitive deficits and loss of vision. It is caused by a loss of function of...
BACKGROUND
Mucolipidosis IV (MLIV) is an autosomal recessive pediatric disease that leads to motor and cognitive deficits and loss of vision. It is caused by a loss of function of the lysosomal channel transient receptor potential mucolipin-1 and is associated with an early pro-inflammatory brain phenotype, including increased cytokine expression. The goal of the current study was to determine whether blood cytokines are linked to motor dysfunction in patients with MLIV and reflect brain inflammatory changes observed in an MLIV mouse model.
METHODS
To determine the relationship between blood cytokines and motor function, we collected plasma from MLIV patients and parental controls concomitantly with assessment of motor function using the Brief Assessment of Motor Function and Modified Ashworth scales. We then compared these profiles with cytokine profiles in brain and plasma samples collected from the mouse model of MLIV.
RESULTS
We found that MLIV patients had prominently increased cytokine levels compared to familial controls and identified profiles of cytokines correlated with motor dysfunction, including IFN-γ, IFN-α2, and IP-10. We found that IP-10 was a key differentiating factor separating MLIV cases from controls based on data from human plasma, mouse plasma, and mouse brain.
CONCLUSIONS
Our data indicate that MLIV is characterized by increased blood cytokines, which are strongly related to underlying neurological and functional deficits in MLIV patients. Moreover, our data identify the interferon pro-inflammatory axis in both human and mouse signatures, suggesting that interferon signaling is an important aspect of MLIV pathology.
Topics: Animals; Chemokine CXCL10; Cytokines; Disease Models, Animal; Humans; Interferons; Mice; Mucolipidoses; Transient Receptor Potential Channels
PubMed: 35159355
DOI: 10.3390/cells11030546 -
Pediatric Radiology 1985Nine of 56 patients with mucopolysaccharidoses (MPS) showed small tracheal diameters on their frontal chest radiographs. Autopsy of an MPS I-H (Hurler disease) patient...
Nine of 56 patients with mucopolysaccharidoses (MPS) showed small tracheal diameters on their frontal chest radiographs. Autopsy of an MPS I-H (Hurler disease) patient demonstrated that the small calibre was secondary to deposition of glycosaminoglycan (mucopolysaccharide). Autopsies of two patients with other storage diseases, one with geleophysic dysplasia and one with mucolipidosis II, also exhibited compromise of their airways because of storage material accumulation.
Topics: Adolescent; Child; Child, Preschool; Humans; Mucolipidoses; Mucopolysaccharidoses; Radiography; Trachea; Tracheal Diseases
PubMed: 3923421
DOI: 10.1007/BF02388760 -
Pediatric Neurology Jul 2007
Topics: Diagnosis, Differential; Humans; Mucolipidoses; Papilledema; Tay-Sachs Disease
PubMed: 17628229
DOI: 10.1016/j.pediatrneurol.2007.04.011