Molecular analysis of the CHD7 gene in CHARGE syndrome: identification of 22 novel mutations and evidence for a low contribution of large CHD7 deletions

Abstract The CHARGE (coloboma, heart defects, atresia, retardation, genital, ear) syndrome is a genetic disease characterized by ocular coloboma, choanal atresia or stenosis and semicircular canal abnormalities. Most of the patients clinically diagnosed with CHARGE syndrome have mutations in chromodomain helicase DNA-binding protein 7 (CHD7) gene. The CHD7 gene is located on chromosome 8q12.1, and up to now, there are more than 500 pathogenic mutations identified in the literature. We report two patients diagnosed with CHARGE syndrome with two novel mutations in the CHD7 gene: the first patient has double consecutive novel mutations in three adjacent codons, and the other has a novel insertion.

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Identification of three novel mutations in the CHD7 gene in patients with clinical signs of typical or atypical CHARGE syndrome

International Journal of Pediatric Otorhinolaryngology ◽

10.1016/j.ijporl.2010.09.006 ◽

2010 ◽

Vol 74 (12) ◽

pp. 1441-1444 ◽

Cited By ~ 4

Author(s):

Angela Michelucci ◽

Paolo Ghirri ◽

Paola Iacopetti ◽

Maria Elena Conidi ◽

Antonella Fogli ◽

...

Keyword(s):

Clinical Signs ◽

Charge Syndrome ◽

Novel Mutations ◽

Chd7 Gene

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Molecular Analysis of Factor VIII and Factor IX Genes in Hemophilia Patients: Identification of Novel Mutations and Molecular Dynamics Studies

Journal of Clinical Medicine Research ◽

10.14740/jocmr2876w ◽

2017 ◽

Vol 9 (4) ◽

pp. 317-331

Author(s):

Faisal A. Al-Allaf ◽

Mohiuddin M. Taher ◽

Zainularifeen Abduljaleel ◽

Abdellatif Bouazzaoui ◽

Mohammed Athar ◽

...

Keyword(s):

Molecular Dynamics ◽

Factor Viii ◽

Molecular Analysis ◽

Factor Ix ◽

Novel Mutations

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Novel pathogenic XK mutations in McLeod syndrome and interaction between XK protein and chorein

Neurology Genetics ◽

10.1212/nxg.0000000000000328 ◽

2019 ◽

Vol 5 (3) ◽

pp. e328 ◽

Cited By ~ 2

Author(s):

Yuka Urata ◽

Masayuki Nakamura ◽

Natsuki Sasaki ◽

Nari Shiokawa ◽

Yoshiaki Nishida ◽

...

Keyword(s):

Membrane Proteins ◽

Erythrocyte Membrane ◽

Molecular Analysis ◽

Cultured Cells ◽

Immunoblot Analysis ◽

Erythrocyte Membranes ◽

Onset Age ◽

Novel Mutations ◽

Erythrocyte Membrane Proteins ◽

Normal Controls

ObjectiveTo identify XK pathologic mutations in 6 patients with suspected McLeod syndrome (MLS) and a possible interaction between the chorea-acanthocytosis (ChAc)- and MLS-responsible proteins: chorein and XK protein.MethodsErythrocyte membrane proteins from patients with suspected MLS and patients with ChAc, ChAc mutant carriers, and normal controls were analyzed by XK and chorein immunoblotting. We performed mutation analysis and XK immunoblotting to molecularly diagnose the patients with suspected MLS. Lysates of cultured cells were co-immunoprecipitated with anti-XK and anti-chorein antibodies.ResultsAll suspected MLS cases were molecularly diagnosed with MLS, and novel mutations were identified. The average onset age was 46.8 ± 8 years, which was older than that of the patients with ChAc. The immunoblot analysis revealed remarkably reduced chorein immunoreactivity in all patients with MLS. The immunoprecipitation analysis indicated a direct or indirect chorein-XK interaction.ConclusionsIn this study, XK pathogenic mutations were identified in all 6 MLS cases, including novel mutations. Chorein immunoreactions were significantly reduced in MLS erythrocyte membranes. In addition, we demonstrated a possible interaction between the chorein and XK protein via molecular analysis. The reduction in chorein expression is similar to that between Kell antigens and XK protein, although the chorein-XK interaction is a possibly noncovalent binding unlike the covalent Kell-XK complex. Our results suggest that reduced chorein levels following lack of XK protein are possibly associated with molecular pathogenesis in MLS.

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De Novo Duplication in the CHD7 Gene Associated With Severe CHARGE Syndrome

Genomics Insights ◽

10.1177/1178631019839010 ◽

2019 ◽

Vol 12 ◽

pp. 117863101983901 ◽

Cited By ~ 1

Author(s):

Laura Pranckėnienė ◽

Eglė Preikšaitienė ◽

Lucie Gueneau ◽

Alexandre Reymond ◽

Vaidutis Kučinskas

Keyword(s):

Umbilical Hernia ◽

Developmental Disorder ◽

Autosomal Dominant ◽

De Novo ◽

Choanal Atresia ◽

Sensory System ◽

Charge Syndrome ◽

Linea Alba ◽

Congenital Hernia ◽

Chd7 Gene

CHARGE syndrome is an autosomal dominant developmental disorder associated with a constellation of traits involving almost every organ and sensory system, in particular congenital anomalies, including choanal atresia and malformations of the heart, inner ear, and retina. Variants in CHD7 have been shown to cause CHARGE syndrome. Here, we report the identification of a novel de novo p.Asp2119_Pro2120ins6 duplication variant in a conserved region of CHD7 in a severely affected boy presenting with 3 and 5 of the CHARGE cardinal major and minor signs, respectively, combined with congenital umbilical hernia, congenital hernia at the linea alba, mildly hypoplastic inferior vermis, slight dilatation of the lateral ventricles, prominent metopic ridge, and hypoglycemic episodes.

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