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OBJECTIVE@#To analyze the clinical presentation and gene of 2 pedigrees with suspected oculocutaneous albinism(OCA), and provide basis for clinical classification, genetic counseling and prenatal diagnosis.@*METHODS@#Variants were identified using next-generation sequencing(NGS) and confirmed by Sanger sequencing in 2 pedigrees with suspected OCA. The pathogenicity of the variants was analyzed according to the American College of Medical Genetics and Genomics (ACMG) standard.@*RESULTS@#Two compound heterozygous mutations of TYR and OCA2 genes were identified respectively in 2 pedigrees with suspected OCA. The mutation of c.819+3insATATGCC in TYR and the mutation of c.1870G>C in OCA2 are first reported in this study. The pathogenicity analysis shows that two novel mutations are likely pathogenic by combination of prediction of SIFT, Polyphen-2 and Human Splicing Finder.@*CONCLUSION@#The findings of this study expand the mutational spectrum of OCA. Compound heterozygous mutations in the TYR and OCA2 gene may be responsible for clinical manifestations of 2 pedigrees with suspected OCA.
Subject(s)
Female , Humans , Pregnancy , Albinism, Oculocutaneous , DNA Mutational Analysis , High-Throughput Nucleotide Sequencing , Membrane Transport Proteins , Monophenol Monooxygenase , Mutation , PedigreeABSTRACT
Objective To explore the pathogenesis of Russell-Silver syndrome (RSS). Methods Two milliliter peripheral blood samples were collected from 6 male patients aged 6 to 8 years with suspected RSS phenotype, the parents of 2 patients and 5 healthy boys. Mononuclear cells were isolated and genomic DNA was extracted. The methylation level of the H19 imprinting control region(ICR)1 on chromosome 11p15.5 was detected by pyrosequencing.The methylation status and the copy number variation in the corresponding region of one RSS patient with positive results by pyrosequencing were analysed by methylation-specific multiplex-ligation-dependent probe amplification assay (MS-MLPA). Results Pyrosequencing analysis revealed that the methylation rates on the 6 CpG targeting sites in H19 differentially methylated region(DMR)in the 6 RSS patients were about 11%~29%, which were significantly lower than those in their parents and normal controls (44%~59%). The MS-MLPA results of one patient with positive pyrosequencing showed that the methylation rates of 4 sites in H19-DMR were about 10%,which was obviously lower than the normal level.The methylation rates of the 4 sites in KCNQ1OT1 gene were about 50%, which was in the normal range. The copy number variations from all samples detected were in the normal range. Conclusion There is methylation aberration of H19-DMR in ICR1 in children with RSS.
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Objective To explore the clinical manifestation, imaging examination, treatment and prognosis of Alagille syndrome in a child combined with hepatocellular carcinoma. Method The clinical manifestation, assistant examination and diagnosis of Alagille syndrome combined with hepatocellular carcinoma were analyzed in the child, and the pertinent literature were reviewed. Results The 6-year-old girl was admitted to hospital for repeated jaundice, and had a history of cardiac surgery. After admission, the patient was found to have a typical face look such as frontal bossing, sunken eyes, pointed chin and hypertrophy of nasal tip. Blood biochemistry showed intrahepatic cholestasis and increased alpha-fetoprotein. Abdominal ultrasonography revealed diffuse multiple solid lesions in the liver. And magnetic resonance imaging of the liver indicated that the liver was enlarged and multiple solid space occupying masses. Jagged 1 gene detection showed heterozygosis mutation of c.1205delC. Conclusion Alagllie syndrome complicated with hepatocellular carcinoma in childhood is extremely rare, and early diagnosis and long-term follow-up are of positive significance for its treatment and prognosis.