Random X inactivation resulting in mosaic nullisomy of region Xp21.1→p21.3 associated with heterozygosity for ornithine transcarbamylase deficiency and for chronic granulomatous disease

1984 ◽  
Vol 38 (4) ◽  
pp. 298-307 ◽  
Author(s):  
U. Francke
Keyword(s):  
Chronic Granulomatous Disease ◽  
Ornithine Transcarbamylase ◽  
X Inactivation ◽  
Granulomatous Disease ◽  
Ornithine Transcarbamylase Deficiency

scholarly journals Origin of mutations in two families with X-linked chronic granulomatous disease

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 602-606 ◽  
Author(s):  
U Francke ◽  
HD Ochs ◽  
BT Darras ◽  
A Swaroop
Keyword(s):  
Chronic Granulomatous Disease ◽  
X Chromosome ◽  
Small Chromosome ◽  
X Inactivation ◽  
Complete Agreement ◽  
Polymorphism Analysis ◽  
Variant Form ◽  
Granulomatous Disease ◽  
Cytochrome B558 ◽  
Fetal Blood Sampling

Abstract The most common X-linked recessive form of chronic granulomatous disease (X-CGD) is characterized by the absence of cytochrome b558 in neutrophils. In a rare variant form of X-CGD, cytochrome b558 is present but not functional. The gene (locus symbol CYBB) was localized to band Xp21 by studies of patients with small chromosome deletions. The gene was cloned based on its location and found to encode the 91-Kd subunit of the cytochrome b558 complex. Most female carriers for X-CGD can be identified by their X-inactivation mosaicism; on average 50% of their neutrophils express the mutant phenotype and fail to reduce nitroblue tetrazolium (NBT). In 2 of 4 families studied, the maternal grandmothers had normal NBT tests, suggesting either nonrandom X- inactivation or new mutations. Restriction fragment length polymorphism analysis using closely linked flanking markers or the NsiI polymorphism detected by the CYBB probe itself, allowed us to identify the X chromosome carrying the mutation as derived from a healthy NBT-positive maternal grandfather. The mothers of the affected boys must have received a paternal X chromosome carrying a new mutation, consistent with the maternal grandmothers' normal NBT tests. In all of eight potential carriers studied, the results of the NBT and DNA marker testing were in complete agreement. Prenatal diagnosis by DNA testing can be performed in early gestation obviating the need for fetal blood sampling.

scholarly journals Origin of mutations in two families with X-linked chronic granulomatous disease

Blood ◽  
1990 ◽  
Vol 76 (3) ◽  
pp. 602-606
Author(s):  
U Francke ◽  
HD Ochs ◽  
BT Darras ◽  
A Swaroop
Keyword(s):  
Chronic Granulomatous Disease ◽  
X Chromosome ◽  
Small Chromosome ◽  
X Inactivation ◽  
Complete Agreement ◽  
Polymorphism Analysis ◽  
Variant Form ◽  
Granulomatous Disease ◽  
Cytochrome B558 ◽  
Fetal Blood Sampling

The most common X-linked recessive form of chronic granulomatous disease (X-CGD) is characterized by the absence of cytochrome b558 in neutrophils. In a rare variant form of X-CGD, cytochrome b558 is present but not functional. The gene (locus symbol CYBB) was localized to band Xp21 by studies of patients with small chromosome deletions. The gene was cloned based on its location and found to encode the 91-Kd subunit of the cytochrome b558 complex. Most female carriers for X-CGD can be identified by their X-inactivation mosaicism; on average 50% of their neutrophils express the mutant phenotype and fail to reduce nitroblue tetrazolium (NBT). In 2 of 4 families studied, the maternal grandmothers had normal NBT tests, suggesting either nonrandom X- inactivation or new mutations. Restriction fragment length polymorphism analysis using closely linked flanking markers or the NsiI polymorphism detected by the CYBB probe itself, allowed us to identify the X chromosome carrying the mutation as derived from a healthy NBT-positive maternal grandfather. The mothers of the affected boys must have received a paternal X chromosome carrying a new mutation, consistent with the maternal grandmothers' normal NBT tests. In all of eight potential carriers studied, the results of the NBT and DNA marker testing were in complete agreement. Prenatal diagnosis by DNA testing can be performed in early gestation obviating the need for fetal blood sampling.

scholarly journals Skewed X-inactivation in a Female Carrier with X-linked Chronic Granulomatous Disease

2019 ◽  
Author(s):  
Itzel López-Hernández ◽  
Caroline Deswarte ◽  
Miguel Ángel Alcantara-Ortigoza ◽  
María del Mar Saez-de-Ocariz ◽  
Marco Antonio Yamazaki-Nakashimada ◽  
...  
Keyword(s):  
Chronic Granulomatous Disease ◽  
De Novo ◽  
X Inactivation ◽  
De Novo Mutation ◽  
Female Carrier ◽  
Reactive Oxygen Metabolites ◽  
Granulomatous Disease ◽  
Oxygen Metabolites ◽  
Skewed X Inactivation ◽  
Skewed X Chromosome Inactivation

Chronic granulomatous disease (CGD) is a primary immunodeficiency caused by defective phagocytic NADPH oxidase, causing a complete lack or significant decrease in the production of microbicidal reactive oxygen metabolites. It mainly affects male children; however, there are scarce reports of adult females diagnosed with X-linked-CGD attributed to an extremely skewed X-chromosome inactivation. This condition is characterized by severe and recurrent infections that usually develop after childhood. In clinical practice, physicians who usually confront these patients should suspect this entity and differentiate it from a secondary immunodeficiency. Here, we report a 38-year-old Mexican female with juvenile-onset X linked-CGD, caused by a de novo mutation and extremely skewed X-inactivation, whose clinical features were similar to those in patients with classic X-linked-CDG.

X-linked chronic granulomatous disease in a female carrier with novel pathogenic mutation and skewed X-inactivation

2018 ◽  
Vol 120 (3) ◽  
pp. 328-329
Author(s):  
Joana Barroso Amaral ◽  
Artur Augusto Paiva ◽  
Fabiana Viana Ramos ◽  
Marie José Stasia ◽  
Sónia Gaspar Lemos
Keyword(s):  
Chronic Granulomatous Disease ◽  
Pathogenic Mutation ◽  
X Inactivation ◽  
Female Carrier ◽  
Granulomatous Disease ◽  
Skewed X Inactivation
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