[Clinical features and genetic analysis of a Chinese pedigree affected with X-linked adrenoleukodystrophy].

OBJECTIVE: To analyze the clinical features and variants of ABCD1 gene in a Chinese pedigree affected with X-linked adrenoleukodystrophy. METHODS: Clinical data of the proband were collected and analyzed. Potential variant of the ABCD1 gene were analyzed by PCR and Sanger sequencing of the proband, his parents and 100 unrelated healthy individuals. RESULTS: The prominent features of the proband included cerebellar and brainstem lesions, along with increased serum level of very-long chain fatty acids. He was found to harbor a hemizygous c.1509delG (p.L504Sfs*54) variant of the ABCD1 gene, for which his mother was heterozygous. The same variant was not detected in his father and 100 healthy controls. CONCLUSION: X-linked adrenoleukodystrophy has a variety of clinical manifestations. Discovery of the c.1509delG (p.L504Sfs*54), as a novel pathogenic variant of the ABCD1 gene, has enabled diagnosis and genetic counseling for this pedigree.

GALC mutations in Chinese patients with late-onset Krabbe disease: a case report.

BACKGROUND: Krabbe disease (also known as globoid cell leukodystrophy) cause by a deficiency of the enzyme ß-galactocerebrosidase (galactosylceramidase, GALC). The deficiency of GALC leads to accumulation of galactosylceramide and psychosine, the latter GALC substrate having a potential role in triggering demyelination. Typically, the disease has an infantile onset, with rapid deterioration in the first few months, leading to death before the age of 2 years. The late onset forms (late-infantile, juvenile, and adult forms) are rare with variable clinical outcomes, presenting spastic paraplegia as the main symptom. CASE PRESENTATION: We recruited a family with two affected individuals. The proband (Patient 1), a 25-year-old male, was presented with slow progressive symptoms, including spastic gait disturbance and vision loss since the 5th year of life. His elder sister (Patient 2), became wheelchair-bound and demented at the age of 22 years. Brain magnetic resonance imaging (MRI) showed increased signal intensity in the white matter along with the involvement of the bilateral corticospinal tracts. GALC deficiency was confirmed by biochemical analysis. DNA sequencing revealed two mutations (c.865G > C: p. G289R and c.136G > T: p. D46Y) in GALC. The clinical characteristics, brain MRI, biochemical and molecular findings led to the diagnosis of Krabbe disease. CONCLUSION: Clinical and neuroimaged signs, positive enzymatic analysis and molecular data converged to definite diagnosis in this neurodegenerative disease.

[High expression of hepatoma associated antigen HAb18G in prokaryotic cells and study on its function in vitro].

AIM: To construct prokaryotic expression vector of HAb18G, and express high level of this fusion protein in E. coli and to identify its function and immunogenicity. METHODS: The HAb18G full length cDNA from pBluescript/HAb18G was obtained by PCR and cloned into prokaryotic expression vector pRSET-C and then transformed into E. coli BL21(DE3) to induce its expression. Expressed products were analyzed by SDS-PAGE and laser thin layer scan. The purified HAb18G protein was identified by gelatin enzymogram and ELISA. RESULTS: Endonuclease digestion and DNA sequencing proved that HAb18G cDNA was cloned correctly into the expression vector. Result of SDS-PAGE showed that the relative molecular mass of the expressed product HAb18G fusion protein was 34,600, which was in accordance with predicted relative molecular mass value. Laser thin layer scan showed that the expressed product accounted for 33% of the total bacteria protein. Result of enzymogram was negative whereas the result of ELISA was positive. CONCLUSION: It was testified that the protein HAb18G has immunogenicity but no bioactivity. The high level prokaryotic expression of HAb18G lay the foundation for manufacturing the HAb18G protein in great quantities and proceeding to its relative research.