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Conclusions: The mutation c.508_511dup in GJB2 gene has been incorrectly named as other mutations. It is essential to standardize mutation nomenclature to describe complex mutations., Objectives: This paper aimed to verify a series of patients with the frame-shift mutation c.508_511dup in the GJB2 gene and review the literature on related mutations., Methods: All the included patients with non-syndromic hearing loss (NSHL) carried the 504insAACG or c.508_511dup mutation of the GJB2 gene in the present study. Their parents were encouraged to participate. After written informed consent and clinic data had been obtained, genomic DNA was extracted from venous blood of participants. The target fragments were amplified by polymerase chain reaction (PCR) and subjected to bidirectional sequencing to identify sequence variations., Results: A total of 14 patients with prelingual NSHL and 6 normal parents were recruited. Genotyping revealed that one mutation, c.508_511dup (not 504insAACG), was homozygous in 1 patient, heterozygous in 2 patients and 3 parents, and compound heterozygous in 11 patients. Twelve patients had hearing loss caused by c.508_511dup in a homozygous or compound heterozygous form, and further study showed that it was wrongly named as 504insAACG. Additionally, according to the standard nomenclature, the previously reported mutations with distinct names from the literature review may be replaced by c.508_511dup.

Angiomyolipoma (AML) is a rare tumor mainly arising in the kidney. Here we report the case of a 55-year-old woman with malignant epithelioid angiomyolipoma with p53 gene mutation. After 7 years from radical nephrectomy of the left kidney, the patient developed multiple lung metastases that showed morphologic features overlapping those of the previously lesion, which was misdiagnosed as renal cell carcinoma. Both renal and pulmonary tumors were reevaluated by immunohistochemical assay, which were showed positive for HMB-45 and p53 protein (95%), but negative for epithelial markers and S-100 protein. A correct diagnosis of malignant epithelioid angiomyolipoma was made on the basis of those results. Meanwhile exon 8 mutation of p53 gene was detected in the renal tumor by microdissection-PCR-SSCP and sequencing technique indicating that p53 gene mutation may play an important role in malignant transformation. The patient was died of respiratory failure after 15 years' follow-up. This is the second report of renal malignant angiomyolipoma with p53 gene mutation.

It is known that enlarged vestibular aqueduct syndrome is closely related to the SLC26A4 mutation. Up to date, more than 200 of SLC26A4 mutations have been described, and novel mutations are being continually identified in different countries and ethnic groups. In this study, two novel variations were identified in a Chinese family associated with enlarged vestibular aqueduct. The two novel substitutions, c.232T>C and c.2006A>T, were detected in exon 3 and exon 17 of the pendrin encoding gene, respectively. The T/C transversion at 232 nucleotide caused p.Y78H mutation while the A/T transversion at 2006 nucleotide caused p.D669V mutation., (Copyright 2010 Elsevier Ireland Ltd. All rights reserved.)

Objective: To study the clinicopathologic features of gastrointestinal stromal tumor (GIST) of small intestine with lymph node metastasis and evaluate the respond to imatinib mesylate (Glivec) therapy., Methods: Two cases of GIST of small intestine associated with lymph node metastasis were collected and investigated by light microscopy and immunohistochemistry. Mutation in exon 9, 11 and of c-kit gene were analyzed by polymerase chain reaction and DNA sequencing., Results: The cases presented as small intestinal mass of irregular shape. Histologically, the tumors consisted of epithelioid and spindled cells, with areas of coagulative necrosis and hemorrhage. The mitotic count measured about 2 per 50 high-power fields. Immunohistochemical study showed that the tumor cells were diffusely distributed and strongly positive for CD117. Mutation analysis revealed that case 1 had an in-frame deletion of 11 amino-acid residues corresponding to 559-569 and carried two missense mutations involving codons 570, 571 in exon 11 of c-kit gene. Case 2 revealed an in-frame deletion involved condons 559-565 in exon 11 of c-kit gene. These two cases were all underwent primary chemotherapy with imatinib mesylate and without new tumor was found during follow-up periods (18, 26 months) after operation., Conclusions: GIST with nodal metastasis is very rare and needs to be distinguished from other soft tissue sarcomas occurring in this site. The responsiveness to imatinib mesylate therapy correlates with the mutation status of c-kit gene.

Objective: The aim of this study was to investigate the effect of mutations of the forkhead transcription factor 2 (FOXL2) gene on the primary and secondary structure of the coded protein and seek for the molecular mechanism of blepharophimosis-ptosis-epicanthus inversus syndrome (BPES)., Methods: The genomic DNA was extracted from peripheral blood of 7 clinically diagnosed BPES patients, PCR amplification of FOXL2 coding region and 5' untranslated region were performed. Sequence analysis was performed using the PCR or cloning products. The structure of the protein was predicted with PDH and ExPASy software, and the difference between the normal and the mutational protein was analyzed., Results: A 901- 930 dup 30 mutation of FOXL2 was found in two patients from a BPES family of type II and a sporadic case, and no any mutations were detected in normal control. Analysis of the primary structure displayed that the molecular weight of the protein coded by the mutated gene was greater than the normal, but both have the same isoelectric point. Analysis of the secondary structure showed that FOXL2 was a transmembrane protein with a polyalanine tract which contained a alpha-helix. When the polyalanine tract expanded, the helix region extended, as a result, the proportion of alpha-helix increased by 4.1%, but the proportions of beta-pleated sheet and random coil decreased correspondingly., Conclusion: Our results suggest that the 901 - 930 dup 30 mutation of FOXL2 is a novel finding. Moreover, this mutation causes great changes in the primary and secondary structure of the coded protein, which may be the molecular pathogenesis of BPES.

Objective: We have studied 4 generations 12 patients in a family which has blepharophimosis-ptosis-epicanthus-inversus syndrome (BPES) for the gene, FOXL2, the group also have 12 normal members in this family and other 80 normal individuals for contrast., Methods: The FOXL2 gene was amplified by polymerase chain reaction and then analyzed by direct genomic sequencing., Results: A 892C > T at nucleotides in FOXL2 was found in the twelve affected patients. No mutations was found in any of the health members in the family., Conclusions: FOXL2 may be a important pathogenesis for the disease in this Chinese family.

Objective: To screen mutations in the forkhead transcriptional factor 2 gene (FOXL2) in six Chinese families with blepharophimosis, ptosis, and epicanthus inversus syndrome(BPES)., Methods: PCR amplification and direct sequencing of the FOXL2 coding region in genomic DNA were performed in affected patients and 80 healthy controls. BLAST analysis of the sequence was made on Internet., Results: A novel 951-953(delC) was found in the two affected patients of a Chinese family with BPES. No mutations were found in the healthy controls. The 951-953(delC) may cause a frameshift mutation after codon 238 that exists downstream of the forkhead domain, resulting in the production of truncated proteins., Conclusion: These findings indicated that the 951-953(delC) deletion mutation in the two patients resulted in truncated proteins and hence led to their BPES. To the authors' knowledge, the 951-953(delC) in FOXL2 has not been previously reported.

Objective To report 2 pedigrees of early⁃onset familial Alzheimer's disease (EOFAD) caused by PSEN1 gene mutation, review previous studies and summarize the PSEN1 gene mutation sites, clinical presentation and genotype characteristics of EOFAD in China. Methods and Results The clinical data of 2 pedigrees with EOFAD from Beijing Tiantan Hospital, Capital Medical University were collected. Genomic DNA from peripheral venous blood of the proband was screened. Search the reported Chinese cases of EOFAD caused by PSEN1 gene mutation. In the Case 1 family, there were 3 members with memory loss, including the proband, onset at the age of 45. His head MRI showed mild atrophy of the cerebral cortex and bilateral hippocampus. A c.488A＞G (p.His163Arg) pathogenic mutation in the exon 6 of PSEN1 gene was found, proving the diagnosis. In the Case 2 family, there were 6 members with memory and working competence loss, including the proband, onset at the age of 42. Head MRI showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. A c.344A＞G (p.Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis. A total of 40 cases (including this 2 cases) of EOFAD patients caused by PSEN1 gene mutation in China were enrolled. Thirty⁃eight pathogenic mutation sites were reported. The age of onset ranged from 21 to 62 years old, and the course of disease ranged from 4 to 10 years. About 87.50% (35/40) of the patients' onset manifestation was progressive memory loss and then rapidly with multiple cognitive domains involved. Some patients manifested with extrapyramidal symptoms, epilepsy or ear symptoms. Conclusions c.488A＞G and c.344A＞G mutations in the PSEN1 gene were identified to cause EOFAD, and c.344A＞G mutation is the first report in China. EOFAD occurs early and progresses rapidly, and sometimes the initial symptoms may be atypical. Therefore, gene detection plays an important role in the diagnosis of the disease.

Objective To report 2 pedigrees of early - onset familial Alzheimer's disease (EOFAD) caused by PSEN1 gene mutation, review previous studies and summarize the PSEN1 gene mutation sites, clinical presentation and genotype characteristics of EOFAD in China. Methods and Results The clinical data of 2 pedigrees with EOFAD from Beijing Tiantan Hospital, Capital Medical University were collected. Genomic DNA from peripheral venous blood of the proband was screened. Search the reported Chinese cases of EOFAD caused by PSEN1 gene mutation. In the Case 1 family, there were 3 members with memory loss, including the proband, onset at the age of 45. His head MRI showed mild atrophy of the cerebral cortex and bilateral hippocampus. A c.488A > G (p.His163Arg) pathogenic mutation in the exon 6 of PSEN1 gene was found, proving the diagnosis. In the Case 2 family, there were 6 members with memory and working competence loss, including the proband, onset at the age of 42. Head MRI showed whole cerebral cortical atrophy and bilateral hippocampal atrophy, obviously on the left side. A c. 344A > G (p. Tyr115Cys) pathogenic mutation in the exon 5 of PSEN1 gene was found, proving the diagnosis. A total of 40 cases (including this 2 cases) of EOFAD patients caused by PSEN1 gene mutation in China were enrolled. Thirty-eight pathogenic mutation sites were reported. The age of onset ranged from 21 to 62 years old, and the course of disease ranged from 4 to 10 years. About 87.50% (35/40) of the patients' onset manifestation was progressive memory loss and then rapidly with multiple cognitive domains involved. Some patients manifested with extrapyramidal symptoms, epilepsy or ear symptoms. Conclusions c.488A > G and c.344A > G mutations in the PSEN1 gene were identified to cause EOFAD, and c.344A > G mutation is the first report in China. EOFAD occurs early and progresses rapidly, and sometimes the initial symptoms may be atypical. Therefore, gene detection plays an important role in the diagnosis of the disease. [ABSTRACT FROM AUTHOR]

Conclusions: The GJB2 gene mutation characteristic of Dongxiang was the interaction result of ethnic background and geographical environment, and Yugur exhibited the typical founder effect. The SLC26A4 gene mutation characteristic of Dongxiang was related to caucasian backgrounds and selection of purpose exons, i.e. ethnic background and the penetrance of ethnic specificity caused the low mtDNA1555A>G mutation frequency in Dongxiang. Objectives: To determine the prevalence of GJB2 and SLC26A4 genes and mtDNA1555A>G mutations and analyze the ethnic specificity in the non-syndromic sensorineural hearing loss (NSHL) of unique ethnic groups in Gansu Province. Methods: Peripheral blood samples were obtained from Dongxiang, Yugur, Bonan, and ethnic Han groups with moderately severe to profound NSHL in Gansu Province. Bidirectional sequencing (or enzyme digestion) was applied to identify the sequence variations. Results: The pathogenic allele frequency of the three gene mutations was different. The frequency of the GJB2 gene among the Dongxiang, Yugur, Bonan, and ethnic Han groups was 9.03%, 12.5%, 5.88%, and 12.17%, respectively. No difference was found between the ethnic groups. The frequencies of the SLC26A4 genes were 3.23%, 8.33%, 0%, and 9.81%, respectively. The mutation frequency of mtDNA1555A>G was 0%, 0%, 0%, and 6.03%, respectively. No difference was found between the ethnic groups, except for the Dongxiang and ethnic Han groups, both in SLC26A4 gene and mtDNA1555A>G. [ABSTRACT FROM AUTHOR]