Faculty Opinions recommendation of Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic.

2021 ◽  
Author(s):  
Y Peng Loh ◽  
Ashley Xiao
Keyword(s):  
Lysosomal Storage Disorder ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Storage Disorder

Rescue of a lysosomal storage disorder caused by Grn loss of function with a brain penetrant progranulin biologic

Cell ◽  
2021 ◽  
Vol 184 (18) ◽  
pp. 4651-4668.e25 ◽  
Author(s):  
Todd Logan ◽  
Matthew J. Simon ◽  
Anil Rana ◽  
Gerald M. Cherf ◽  
Ankita Srivastava ◽  
...  
Keyword(s):  
Lysosomal Storage Disorder ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Storage Disorder

scholarly journals Identification of a novel homozygous loss-of-function mutation in FUCA1 gene causing severe fucosidosis: A case report

2021 ◽  
Vol 49 (4) ◽  
pp. 030006052110059
Author(s):  
Xinwen Zhang ◽  
Shaozhi Zhao ◽  
Hongwei Liu ◽  
Xiaoyan Wang ◽  
Xiaolei Wang ◽  
...  
Keyword(s):  
Amino Acids ◽  
Lysosomal Storage Disorder ◽  
Autosomal Recessive ◽  
Signs And Symptoms ◽  
Lysosomal Storage ◽  
Loss Of Function ◽  
Wild Type ◽  
Single Nucleotide ◽  
Whole Exome ◽  
Exon 1

Fucosidosis is a rare lysosomal storage disorder characterized by deficiency of α-L-fucosidase with an autosomal recessive mode of inheritance. Here, we describe a 4-year-old Chinese boy with signs and symptoms of fucosidosis but his parents were phenotypically normal. Whole exome sequencing (WES) identified a novel homozygous single nucleotide deletion (c.82delG) in the exon 1 of the FUCA1 gene. This mutation will lead to a frameshift which will result in the formation of a truncated FUCA1 protein (p.Val28Cysfs*105) of 132 amino acids approximately one-third the size of the wild type FUCA1 protein (466 amino acids). Both parents were carrying the mutation in a heterozygous state. This study expands the mutational spectrum of the FUCA1 gene associated with fucosidosis and emphasises the benefits of WES for accurate and timely clinical diagnosis of this rare disease.

A lysosomal storage disorder in mice: A model of Niemann-Pick disease

1982 ◽  
Vol 5 (4) ◽  
pp. 239-240 ◽  
Author(s):  
T. Sakiyama ◽  
M. Tsuda ◽  
T. Kitagawa ◽  
R. Fujita ◽  
S. Miyawaki
Keyword(s):  
Lysosomal Storage Disorder ◽  
Lysosomal Storage ◽  
Niemann Pick Disease ◽  
Storage Disorder ◽  
Niemann Pick ◽  
Pick Disease

scholarly journals The Association Between Lysosomal Storage Disorder Genes and Parkinson’s Disease: A Large Cohort Study in Chinese Mainland Population

2021 ◽  
Vol 13 ◽  
Author(s):  
Yu-wen Zhao ◽  
Hong-xu Pan ◽  
Zhenhua Liu ◽  
Yige Wang ◽  
Qian Zeng ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Onset ◽  
Lysosomal Storage Disorder ◽  
Rare Variants ◽  
Late Onset ◽  
Chinese Mainland ◽  
Lysosomal Storage ◽  
Post Translational Modification ◽  
Storage Disorder

Background: Recent years have witnessed an increasing number of studies indicating an essential role of the lysosomal dysfunction in Parkinson’s disease (PD) at the genetic, biochemical, and cellular pathway levels. In this study, we investigated the association between rare variants in lysosomal storage disorder (LSD) genes and Chinese mainland PD.Methods: We explored the association between rare variants of 69 LSD genes and PD in 3,879 patients and 2,931 controls from Parkinson’s Disease & Movement Disorders Multicenter Database and Collaborative Network in China (PD-MDCNC) using next-generation sequencing, which were analyzed by using the optimized sequence kernel association test.Results: We identified the significant burden of rare putative LSD gene variants in Chinese mainland patients with PD. This association was robust in familial or sporadic early-onset patients after excluding the GBA variants but not in sporadic late-onset patients. The burden analysis of variant sets in genes of LSD subgroups revealed a suggestive significant association between variant sets in genes of sphingolipidosis deficiency disorders and familial or sporadic early-onset patients. In contrast, variant sets in genes of sphingolipidoses, mucopolysaccharidoses, and post-translational modification defect disorders were suggestively associated with sporadic late-onset patients. Then, SMPD1 and other four novel genes (i.e., GUSB, CLN6, PPT1, and SCARB2) were suggestively associated with sporadic early-onset or familial patients, whereas GALNS and NAGA were suggestively associated with late-onset patients.Conclusion: Our findings supported the association between LSD genes and PD and revealed several novel risk genes in Chinese mainland patients with PD, which confirmed the importance of lysosomal mechanisms in PD pathogenesis. Moreover, we identified the genetic heterogeneity in early-onset and late-onset of patients with PD, which may provide valuable suggestions for the treatment.

scholarly journals Hyo-Mental Angle and Distance: An Important Adjunct in Airway Assessment of Adult Mucopolysaccharidosis

2021 ◽  
Vol 10 (21) ◽  
pp. 4924
Author(s):  
Chaitanya Gadepalli ◽  
Karolina M. Stepien ◽  
Govind Tol
Keyword(s):  
Lysosomal Storage Disorder ◽  
Hyoid Bone ◽  
Horizontal Axis ◽  
Moderate Correlation ◽  
Lysosomal Storage ◽  
Airway Assessment ◽  
Storage Disorder ◽  
Age Range ◽  
Mps I ◽  
Simpler Method

Background: Mucopolysaccharidosis (MPS) is a rare congenital lysosomal storage disorder with complex airways. High anterior larynx is assessed by thyromental distance (TMD) nasendoscopy. A simpler method to assess this hyoid bone is described. The distance between the central-hyoid and symphysis of the mandible (hyo-mental distance; HMD) and inclination of this line to the horizontal axis (hyo-mental angle; HMA) in neutrally positioned patients is investigated. Methods: HMA, HMD in MPS, and non-MPS were compared, and their correlation with height and weight were assessed. Results: 50 adult MPS patients (M = 32, F = 18, age range = 19–66 years; mean BMI = 26.8 kg/m2) of MPS I, II, III, IV, and VI were compared with 50 non-MPS (M = 25, F = 25; age range = 22–84 years; mean BMI = 26.5 kg/m2). Mean HMA in MPS was 25.72° (−10 to +50) versus 2.42° (−35 to +28) in non-MPS. Mean HMD was 46.5 (25.7–66) millimeters in MPS versus 41.8 (27–60.3) in non-MPS. HMA versus height and weight showed a moderate correlation (r = −0.4, p < 0.05) in MPS and no significant correlation (r < 0.4, p > 0.05) in non-MPS. HMD versus height and weight showed no correlation (r < 0.4, p > 0.05) in both groups. Conclusions: HMA seems more acute in MPS despite nearly the same HMD as non-MPS, signifying a high larynx, which may be missed by TMD.

scholarly journals Association of luteal cell degeneration and progesterone deficiency with lysosomal storage disorder mucolipidosis type IV in Mcoln1−/− mouse model†

2019 ◽  
Vol 101 (4) ◽  
pp. 782-790 ◽  
Author(s):  
Zidao Wang ◽  
Ahmed E El Zowalaty ◽  
Yuehuan Li ◽  
Christian L Andersen ◽  
Xiaoqin Ye
Keyword(s):  
Corpus Luteum ◽  
Lysosomal Storage Disorder ◽  
Luteal Cell ◽  
Lysosomal Storage ◽  
Cell Degeneration ◽  
Mucolipidosis Type Iv ◽  
Type Iv ◽  
Mitochondrial Functions ◽  
Storage Disorder ◽  
Mucolipidosis Type

Abstract Transient receptor potential cation channel, mucolipin subfamily, member 1 (TRPML1) (MCOLN1/Mcoln1) is a lysosomal counter ion channel. Mutations in MCOLN1 cause mucolipidosis type IV (MLIV), a progressive and severe lysosomal storage disorder with a slow onset. Mcoln1−/− mice recapitulate typical MLIV phenotypes but roles of TRPML1 in female reproduction are unknown. Despite normal mating activities, Mcoln1−/− female mice had reduced fertility at 2 months old and quickly became infertile at 5 months old. Progesterone deficiency was detected on 4.5 days post coitum/gestation day 4.5 (D4.5). Immunohistochemistry revealed TRPML1 expression in luteal cells of wild type corpus luteum (CL). Corpus luteum formation was not impaired in 5–6 months old Mcoln1−/− females indicated by comparable CL numbers in control and Mcoln1−/− ovaries on both D1.5 and D4.5. In the 5–6 months old Mcoln1−/− ovaries, histology revealed less defined corpus luteal cord formation, extensive luteal cell vacuolization and degeneration; immunofluorescence revealed disorganized staining of collagen IV, a basal lamina marker for endothelial cells; Nile Red staining detected lipid droplet accumulation, a typical phenotype of MLIV; immunofluorescence of heat shock protein 60 (HSP60, a mitochondrial marker) and in situ hybridization of steroidogenic acute regulatory protein (StAR, for the rate-limiting step of steroidogenesis) showed reduced expression of HSP60 and StAR, indicating impaired mitochondrial functions. Luteal cell degeneration and impaired mitochondrial functions can both contribute to progesterone deficiency in the Mcoln1−/− mice. This study demonstrates a novel function of TRPML1 in maintaining CL luteal cell integrity and function.

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