Clinical and molecular analysis of 6 Chinese patients with isoleucine metabolism defects: identification of 3 novel mutations in the HSD17B10 and ACAT1 gene

Neuronal ceroid lipofuscinosis is a hereditary disease, and ceroid-lipofuscinosis neuronal protein 5 (CLN5) has been proved to be associated with neuronal ceroid lipofuscinosis. Here we report 3 patients from 2 families diagnosed with CLN5 neuronal ceroid lipofuscinosis. Whole genome sequencing of DNAs from 3 patients and their families revealed 3 novel homozygous mutations, including 1 deletion CLN5.c718 719delAT and 2 missense mutations c.1082T>C and c.623G>A. We reviewed 278 papers about neuronal ceroid lipofuscinosis resulting from CLN5 mutations and compared Chinese cases with 27 European and American cases. The overall age of onset of European and American patients occur mainly at 3 to 6 years (66%, 18/27), 100% (27/27) of patients had psychomotor regression, 99% (26/27) patients presented vision decline, and 70% (19/27) of patients suffered seizures. In China, the age of onset in 3 patients was 5 years, but for 1 patient it was at 17 months. Four Chinese patients presented psychomotor deterioration and seizures; only 1 had visual problems.

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Identification of eight novel mutations in 11 Chinese patients with maple syrup urine disease

World Journal of Pediatrics ◽

10.1007/s12519-020-00349-1 ◽

2020 ◽

Vol 16 (4) ◽

pp. 401-410 ◽

Cited By ~ 1

Author(s):

Wei-Hua Sun ◽

Bing-Bing Wu ◽

Ya-Qiong Wang ◽

Meng-Yuan Wu ◽

Xin-Ran Dong ◽

...

Keyword(s):

Maple Syrup Urine Disease ◽

Chinese Patients ◽

Novel Mutations ◽

Maple Syrup ◽

Urine Disease

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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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