scholarly journals Phenotypic Characterization of Intellectual Disability Caused by MBOAT7 Mutation in Two Consanguineous Pakistani Families

2020 ◽  
Vol 8 ◽  
Author(s):  
Liwei Sun ◽  
Amjad Khan ◽  
Han Zhang ◽  
Shirui Han ◽  
Xiaerbati Habulieti ◽  
...  

A homozygous in-frame deletion (c. 758_778del; p. Glu253_Ala259del) in membrane-bound O-acyltransferase family member 7 (MBOAT7), also known as lysophosphatidylinositol acyltransferase (LPIAT1), was previously reported to be the genetic cause of intellectual disability (ID) in consanguineous families from Pakistan. Here, we identified two additional Pakistani consanguineous families with severe ID individuals sharing the same homozygous variant. Thus, we provide further evidence to support this MBOAT7 mutation as a potential founder variant. To understand the genotype-phenotype relationships of the in-frame deletion in the MBOAT7 gene, we located the variant in the fifth transmembrane domain of the protein and determined that it causes steric hindrance to the formation of an α-helix and hydrogen bond, possibly influencing its effectiveness as a functional transmembrane protein. Moreover, extensive neuropsychological observations, clinical interviews and genetic analysis were performed on 6 patients from the 2 families. We characterized the phenotype of the patients and noted the serious outcome of severe paraplegia. Thus, optimal management for symptom alleviation and appropriate screening in these patients are crucial.

1990 ◽  
Vol 10 (9) ◽  
pp. 4658-4666
Author(s):  
A M Buchberg ◽  
H G Bedigian ◽  
N A Jenkins ◽  
N G Copeland

BXH-2 mice have the highest incidence of spontaneous retrovirally induced myeloid leukemia of any known inbred strain and, as such, represent a valuable model system for identifying cellular proto-oncogenes involved in myeloid disease. Chronic murine leukemia viruses often induce disease by insertional activation or mutation of cellular proto-oncogenes. These loci are identified as common viral integration sites in tumor DNAs. Here we report on the characterization of a novel common viral integration site in BXH-2 myeloid leukemias, designated Evi-2. Within the cluster of viral integration sites that define Evi-2, we identified a gene that has the potential for encoding a novel protein of 223 amino acids. This putative proto-oncogene possesses all of the structural features of a transmembrane protein. Within the transmembrane domain is a "leucine zipper," suggesting that Evi-2 is involved in either homopolymer or heteropolymer formation, which may play an important role in the normal functioning of Evi-2. Interestingly, the human homolog of Evi-2 has recently been shown to be tightly linked to the von Recklinghausen neurofibromatosis locus, suggesting a role for Evi-2 in human disease as well.


Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1686-1694 ◽  
Author(s):  
AJ Verhoeven ◽  
BG Bolscher ◽  
LJ Meerhof ◽  
R van Zwieten ◽  
J Keijer ◽  
...  

Abstract Monoclonal antibodies (MoAbs) were raised against cytochrome b558, a membrane-bound component of the NADPH:O2 oxidoreductase in human neutrophils. This cytochrome consists of a low-molecular-weight (low- mol-wt) subunit of 22 to 23 Kd, probably encoded by an autosomal gene, and a high-mol-wt subunit of 75 to 90 Kd, encoded on the X-chromosome. MoAb 449 reacts with the low-mol-wt subunit and MoAb 48 with the high- mol-wt subunit on Western blots of purified cytochrome b558 and on blots of whole neutrophil extracts. In extracts of neutrophils from patients with chronic granulomatous disease (CGD) in which cytochrome b558 is not detectable by spectrophotometric methods, the low-mol-wt subunit is present, albeit in a much smaller amount. The high-mol-wt subunit is not detected by MoAb 48 in neutrophils of patients with X- linked CGD and in neutrophils of patients with the autosomal, cytochrome-b558-negative form of the disease. These results can be explained by a marked instability of these subunits when the synthesis of either of the two is disturbed. In differentiated HL-60 cells, the high-mol-wt subunit appears to be present in a different form. Cloning of the low-mol-wt subunit with the help of MoAb 449 suggests the presence of a heme-binding site on this subunit. By comparison of the binding characteristics of MoAb 449 to intact and permeabilized neutrophils with those of MoAb 7D5, recently isolated by Nakamura et al (Blood 69:1404, 1987), the low-mol-wt subunit was established as a transmembrane protein.


Agronomy ◽  
2021 ◽  
Vol 11 (12) ◽  
pp. 2454
Author(s):  
Zhanyu Chen ◽  
Yushuang Wang ◽  
Yanbo Chen ◽  
Xiaoqin Yang ◽  
Shuang Wang ◽  
...  

Phospholipid N-methyltransferase (PLMT) plays an important role in the synthesis of phosphatidylcholine (PtdCho). The aim of this study was to characterize the molecular properties of GmPLMT and the expression of soybean GmPLMT and its effects on the production of lipid metabolites. Results showed that GmPLMT composed of mainly α-helix was a hydrophobic and transmembrane protein. In soybean leaves, GmPLMT was highly expressed during seedling and flowering stages. In transgenic Arabidopsis thaliana, the highest and lowest expression levels of GmPLMT were detected at flowering and maturity stages, respectively. The total phospholipid contents in soybean grains were decreased from 7.2% (35 days after flowering) to 4.8% (55 days after flowering) and then increased to 7.0% (75 days after flowering). The contents of PtdCho showed a similar pattern to that of total phospholipids. In transgenic A. thaliana seeds, the contents of total phospholipids and PtdCho were significantly increased. Significantly positive correlations were revealed between expression of GmPLMT and contents of both PtdCho and crude fats, and between the contents of PtdCho and both linoleic acid and linolenic acid, suggesting that increased expression of GmPLMT improved the production of lipid metabolites. This study provided solid experimental evidence for further improvement of soybean quality based on GmPLMT in the molecular breeding of soybeans.


Blood ◽  
1989 ◽  
Vol 73 (6) ◽  
pp. 1686-1694 ◽  
Author(s):  
AJ Verhoeven ◽  
BG Bolscher ◽  
LJ Meerhof ◽  
R van Zwieten ◽  
J Keijer ◽  
...  

Monoclonal antibodies (MoAbs) were raised against cytochrome b558, a membrane-bound component of the NADPH:O2 oxidoreductase in human neutrophils. This cytochrome consists of a low-molecular-weight (low- mol-wt) subunit of 22 to 23 Kd, probably encoded by an autosomal gene, and a high-mol-wt subunit of 75 to 90 Kd, encoded on the X-chromosome. MoAb 449 reacts with the low-mol-wt subunit and MoAb 48 with the high- mol-wt subunit on Western blots of purified cytochrome b558 and on blots of whole neutrophil extracts. In extracts of neutrophils from patients with chronic granulomatous disease (CGD) in which cytochrome b558 is not detectable by spectrophotometric methods, the low-mol-wt subunit is present, albeit in a much smaller amount. The high-mol-wt subunit is not detected by MoAb 48 in neutrophils of patients with X- linked CGD and in neutrophils of patients with the autosomal, cytochrome-b558-negative form of the disease. These results can be explained by a marked instability of these subunits when the synthesis of either of the two is disturbed. In differentiated HL-60 cells, the high-mol-wt subunit appears to be present in a different form. Cloning of the low-mol-wt subunit with the help of MoAb 449 suggests the presence of a heme-binding site on this subunit. By comparison of the binding characteristics of MoAb 449 to intact and permeabilized neutrophils with those of MoAb 7D5, recently isolated by Nakamura et al (Blood 69:1404, 1987), the low-mol-wt subunit was established as a transmembrane protein.


1990 ◽  
Vol 10 (9) ◽  
pp. 4658-4666 ◽  
Author(s):  
A M Buchberg ◽  
H G Bedigian ◽  
N A Jenkins ◽  
N G Copeland

BXH-2 mice have the highest incidence of spontaneous retrovirally induced myeloid leukemia of any known inbred strain and, as such, represent a valuable model system for identifying cellular proto-oncogenes involved in myeloid disease. Chronic murine leukemia viruses often induce disease by insertional activation or mutation of cellular proto-oncogenes. These loci are identified as common viral integration sites in tumor DNAs. Here we report on the characterization of a novel common viral integration site in BXH-2 myeloid leukemias, designated Evi-2. Within the cluster of viral integration sites that define Evi-2, we identified a gene that has the potential for encoding a novel protein of 223 amino acids. This putative proto-oncogene possesses all of the structural features of a transmembrane protein. Within the transmembrane domain is a "leucine zipper," suggesting that Evi-2 is involved in either homopolymer or heteropolymer formation, which may play an important role in the normal functioning of Evi-2. Interestingly, the human homolog of Evi-2 has recently been shown to be tightly linked to the von Recklinghausen neurofibromatosis locus, suggesting a role for Evi-2 in human disease as well.


2021 ◽  
Vol 132 ◽  
pp. S282
Author(s):  
Maxime Cadieux-Dion ◽  
Emily Farrow ◽  
Holly Welsh ◽  
Lauren Bartik ◽  
Caitlin Schwager ◽  
...  

2009 ◽  
Vol 47 (01) ◽  
Author(s):  
K Hochrath ◽  
S Hillebrandt ◽  
F Lammert ◽  
B Rathkolb ◽  
H Fuchs ◽  
...  

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