Genome-wide linkage, exome sequencing and functional analyses identify ABCB6 as the pathogenic gene of dyschromatosis universalis hereditaria.

BACKGROUND: As a genetic disorder of abnormal pigmentation, the molecular basis of dyschromatosis universalis hereditaria (DUH) had remained unclear until recently when ABCB6 was reported as a causative gene of DUH. METHODOLOGY: We performed genome-wide linkage scan using Illumina Human 660W-Quad BeadChip and exome sequencing analyses using Agilent SureSelect Human All Exon Kits in a multiplex Chinese DUH family to identify the pathogenic mutations and verified the candidate mutations using Sanger sequencing. Quantitative RT-PCR and Immunohistochemistry was performed to verify the expression of the pathogenic gene, Zebrafish was also used to confirm the functional role of ABCB6 in melanocytes and pigmentation. RESULTS: Genome-wide linkage (assuming autosomal dominant inheritance mode) and exome sequencing analyses identified ABCB6 as the disease candidate gene by discovering a coding mutation (c.1358C>T; p.Ala453Val) that co-segregates with the disease phenotype. Further mutation analysis of ABCB6 in four other DUH families and two sporadic cases by Sanger sequencing confirmed the mutation (c.1358C>T; p.Ala453Val) and discovered a second, co-segregating coding mutation (c.964A>C; p.Ser322Lys) in one of the four families. Both mutations were heterozygous in DUH patients and not present in the 1000 Genome Project and dbSNP database as well as 1,516 unrelated Chinese healthy controls. Expression analysis in human skin and mutagenesis interrogation in zebrafish confirmed the functional role of ABCB6 in melanocytes and pigmentation. Given the involvement of ABCB6 mutations in coloboma, we performed ophthalmological examination of the DUH carriers of ABCB6 mutations and found ocular abnormalities in them. CONCLUSION: Our study has advanced our understanding of DUH pathogenesis and revealed the shared pathological mechanism between pigmentary DUH and ocular coloboma.

Eruptive microvenular hemangiomas in 4 Chinese patients: clinicopathologic correlation and review of the literature.

Microvenular hemangioma (MVH) is an uncommon benign vascular neoplasm that usually occurs as a solitary asymptomatic red or purple papule, nodule, or plaque with a predilection for the upper extremities. Patients with more than 1 lesion, that is, multiple MVHs, are extremely rare. We describe the clinicopathologic features of 4 Chinese patients who had a rapidly progressive abrupt onset of numerous MVHs numbering in the tens to hundreds. Clinically, the correct diagnosis of MVH could not be made in any of our patients; however, histologic examination revealed the characteristic features of MVH. Immunohistochemical stains were performed in all cases and showed the vessel lining cells to be positive for CD34, CD31, and factor VIII-related antigen. Polymerase chain reaction for human herpesvirus-8 was negative in all cases. The differential diagnosis and review of the literature of patients with multiple MVHs are presented.

One novel homozygous mutation of SLC39A4 gene in a Chinese patient with acrodermatitis enteropathica.

Acrodermatitis enteropathica, a rare autosomal recessive disease, manifests as periorificial and symmetrical acral dermatitis, alopecia, and diarrhea due to insufficient zinc uptake by the intestine. Recent research revealed that mutations in the SLC39A4 gene are responsible for acrodermatitis enteropathica. This gene encodes one member of a human zinc transporter-like protein, also known as ZIP4. We detected one novel homozygous mutation c.1115T > G in the human SLC39A4 gene in one Chinese patient, which leading to p.L372R of the ZIP4. Homology analysis shows Leu372 in ZIP4 is conserved in Eutheria.

[The methylation locus and frequency pattern on p16 INK4a gene promoter CpG in epidermis of patients with psoriasis].

OBJECTIVE: To investigate the CpG methylation locus and frequency pattern on p16 INK4a gene promoter in epidermis of p16 INK4a methylated patients with psoriasis vulgaris. METHODS: The DNA specimens were obtained from epidermal lesion of 50 plaque psoriatic patients. Methylation specific PCR and DNA sequencing were used to detect the frequency and locus of methylation in p16 INK4a gene promoter region. RESULTS: Approximately 50% CpG was methylated in p16 INK4a methylated patients, methylation was found in specifical locus of p16 INK4a gene promoter. CONCLUSION: The distinct methylation pattern is showed on the p16 INK4a gene promoter region in patients with psoriasis.

[Comparative proteome analysis of human papillomavirus-infected cervical specimens and the difference between the high- and low-risk genotypes of human papillomavirus].

OBJECTIVE: To perform an comparative proteome analysis of human papillomavirus-infected cervical specimens and to investigate different expressions between high- and low-risk genotypes. METHODS: The cervical specimens were divided into two groups (cervical intraepithelial neoplasia group and condyloma acuminatum group) according to their genotypes. Using comparative proteome technology, high-risk human papillomavirus-infected cervical intraepithelial neoplasia, low-risk human papillomavirus-infected condyloma acuminatum, and normal cervical intraepithelial tissue were compared. The differential expression protein spots were identified by mass spectrometry. RESULTS: Totally 26 differential spots were selected and analyzed, and 22 peptide mass fingerprints (PMF) maps were obtained by MALDI-TOF-MS. Eighteen proteins were preliminarily identified after searching the NCBInr database. The function information of these 18 proteins mainly involved cell metabolism, signal transduction, cell secretion, cell cytoskeleton construction, cell proliferation, and apoptosis. CONCLUSION: The proteomic expressions after the cervical infection of high- or low-risk genotype of human papillomavirus are obviously different.