Novel mutations in theTCIRG1gene encoding the a3 subunit of the vacuolar proton pump in patients affected by infantile malignant osteopetrosis

2003 ◽  
Vol 21 (2) ◽  
pp. 151-157 ◽  
Author(s):  
Jean-Claude Scimeca ◽  
Danielle Quincey ◽  
Hugues Parrinello ◽  
Delphine Romatet ◽  
Josiane Grosgeorge ◽  
...  
Keyword(s):  
Proton Pump ◽  
Novel Mutations ◽  
Malignant Osteopetrosis ◽  
A3 Subunit ◽  
Infantile Malignant Osteopetrosis ◽  
Vacuolar Proton Pump

scholarly journals Two novel mutations in TCIRG1 induced infantile malignant osteopetrosis: a case report

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Ping Wu ◽  
Zhe Cai ◽  
Wen-Hui Jiang ◽  
Gen Lu ◽  
Pei-Qiong Wu ◽  
...  
Keyword(s):  
Bone Density ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
High Precision ◽  
Radiographic Examination ◽  
Mineral Density ◽  
Novel Mutations ◽  
Whole Exome ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis

Abstract Background Infantile malignant osteopetrosis (IMO) is a rare autosomal recessive disease characterized by a higher bone density in bone marrow caused by the dysfunction of bone resorption. Clinically, IMO can be diagnosed with medical examination, bone mineral density test and whole genome sequencing. Case presentation We present the case of a 4-month-old male infant with abnormal skull development, hypocalcemia and premature closure of the cranial sutures. Due to the hyper bone density showed by his radiographic examination, which are characteristic patterns of IMO, we speculated that he might be an IMO patient. In order to confirm this diagnosis, a high-precision whole exome sequencing of the infant and his parents was performed. The analysis of high-precision whole exome sequencing results lead to the identification of two novel heterozygous mutations c.504-1G > C (a splicing site mutation) and c.1371delC (p.G458Afs*70, a frameshift mutation) in gene TCIRG1 derived from his parents. Therefore, we propose that there is a close association between these two mutations and the onset of IMO. Conclusions To date, these two novel mutations in gene TCIRG1 have not been reported in the reference gene database of Chinese population. These variants have likewise not been reported outside of China in the Genome Aggregation Database (gnomAD). Our case suggests that the use of whole exome sequencing to detect these two mutations will improve the identification and early diagnosis of IMO, and more specifically, the identification of homozygous individuals with TCIRG1 gene mutation. We propose that these mutations in gene TCIRG1 could be a novel therapeutic target for the IMO in the future.

scholarly journals Regulatory assembly of the vacuolar proton pump V o V 1 -ATPase in yeast cells by FLIM-FRET

2010 ◽  
Author(s):  
Stefan Ernst ◽  
Claire Batisse ◽  
Nawid Zarrabi ◽  
Bettina Böttcher ◽  
Michael Börsch
Keyword(s):  
Proton Pump ◽  
Yeast Cells ◽  
Vacuolar Proton Pump

scholarly journals Osteopetro-Rickets: A Rare Paradoxical Association in an Infant

2012 ◽  
Vol 32 (1) ◽  
pp. 88-89
Author(s):  
MB Patil
Keyword(s):  
Case Report ◽  
Key Words ◽  
Bone Disease ◽  
Clinical Signs ◽  
Severe Anaemia ◽  
Management Options ◽  
Positive Balance ◽  
Malignant Osteopetrosis ◽  
Infantile Malignant Osteopetrosis ◽  
Key Words Osteopetrosis

Infantile malignant osteopetrosis is a hereditary bone disease with intense positive balance of body calcium. Osteopetro-rickets is a very rare paradoxical association of infantile osteopetrosis and rickets. This is a case report of an infant with osteopetro- rickets. He presented with severe anaemia, splenomegaly, hepatomegaly and clinical signs of rickets. The clinical, biochemical and skeletal survey showed osteopetrosis and rickets. We also describe the pathophysiologic mechanism and various management options. Key words: Osteopetrosis; Osteopetro-rickets; Rickets DOI: http://dx.doi.org/10.3126/jnps.v32i1.5292 J. Nepal Paediatr. Soc. Vol.32(1) 2012 88-89

The COOH termini of NBC3 and the 56-kDa H+-ATPase subunit are PDZ motifs involved in their interaction

2003 ◽  
Vol 284 (3) ◽  
pp. C667-C673 ◽  
Author(s):  
Alexander Pushkin ◽  
Natalia Abuladze ◽  
Debra Newman ◽  
Vladimir Muronets ◽  
Pejvak Sassani ◽  
...  
Keyword(s):  
Amino Acid ◽  
Proton Pump ◽  
Rat Kidney ◽  
Pdz Domain ◽  
Intercalated Cells ◽  
Regulatory Factor ◽  
Atpase Subunit ◽  
Sodium Bicarbonate Cotransporter ◽  
Terminal Amino ◽  
Vacuolar Proton Pump

The electroneutral sodium bicarbonate cotransporter 3 (NBC3) coimmunoprecipitates from renal lysates with the vacuolar H+-ATPase. In renal type A and B intercalated cells, NBC3 colocalizes with the vacuolar H+-ATPase. The involvement of the COOH termini of NBC3 and the 56-kDa subunit of the proton pump in the interaction of these proteins was investigated. The intact and modified COOH termini of NBC3 and the 56-kDa subunit of the proton pump were synthesized, coupled to Sepharose beads, and used to pull down kidney membrane proteins. Both the 56- and the 70-kDa subunits of the proton pump, as well as a PDZ domain containing protein Na+/H+ exchanger regulatory factor 1 (NHERF-1), were bound to the intact 18 amino acid NBC3 COOH terminus. A peptide truncated by five COOH-terminal amino acids did not bind these proteins. Replacement of the COOH-terminal leucine with glycine blocked binding of both the proton pump subunits but did not affect binding of NHERF-1. The 18 amino acid COOH terminus of the 56-kDa subunit of the proton pump bound NHERF-1 and NBC3, but the truncated and modified peptide did not. A complex of NBC3, the 56-kDa subunit of the proton pump, and NHERF-1 was identified in rat kidney. The data indicate that the COOH termini of NBC3 and the 56-kDa subunit of the vacuolar proton pump are PDZ-interacting motifs that are necessary for the interaction of these proteins. NHERF-1 is involved in the interaction of NBC3 and the vacuolar proton pump.

scholarly journals Effects of inhibitors of the vacuolar proton pump on hepatic heterophagy and autophagy

2001 ◽  
Vol 1510 (1-2) ◽  
pp. 243-257 ◽  
Author(s):  
Seyed Ali Mousavi ◽  
Rune Kjeken ◽  
Trond Olav Berg ◽  
Per Ottar Seglen ◽  
Trond Berg ◽  
...  
Keyword(s):  
Proton Pump ◽  
Vacuolar Proton Pump

scholarly journals Association of the 16-kDa Subunit c of Vacuolar Proton Pump with the Ileal Na+-dependent Bile Acid Transporter

2004 ◽  
Vol 279 (16) ◽  
pp. 16295-16300 ◽  
Author(s):  
An-Qiang Sun ◽  
Natarajan Balasubramaniyan ◽  
Chuan-Ju Liu ◽  
Mohammad Shahid ◽  
Frederick J. Suchy
Keyword(s):  
Bile Acid ◽  
Proton Pump ◽  
Subunit C ◽  
Bile Acid Transporter ◽  
Acid Transporter ◽  
Vacuolar Proton Pump
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