Screening for EXT1 and EXT2 gene mutations in a ethnic Han Chinese family from Shanxi with hereditary multiple exostoses / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for potential mutations in an ethnic Han Chinese family from Shanxi with hereditary multiple exostoses.</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to screen potential mutations in EXT1 and EXT2 genes.</p><p><b>RESULTS</b>For EXT1 gene, two synonymous mutations (P477P and E587E), three intronic mutations (c.1537 -48A>G, c.1721 +203A>G and c.1722 -103C>G) were detected. For EXT2 gene, five intronic mutations (c.-29 -148A>T, c.1080 -18T>A, c.1336 -93C>T, c.1526 -166C>T, and c.1526 -195C>T) were identified. Among these, EXT1 P477P, EXT1 E587E and EXT2 c.1080 -18T>A are polymorphisms listed by Multiple Osteochondroma Mutation Database, whilst the other 7 sites have not been reported.</p><p><b>CONCLUSION</b>No mutations have been found among all exons of the EXT1 and EXT2 genes in this family. Linkage analysis is necessary for identifying the cause of this disease.</p>

Study on three common mitochondrial DNA mutations in Leber's hereditary optic neuropathy / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To screen for genetic mutations in 35 patients with Leber's hereditary optic neuropathy (LHON).</p><p><b>METHODS</b>Polymerase chain reaction and DNA sequencing were used to screen for the presence of mitochondrial DNA mutations.</p><p><b>RESULTS</b>The total detection rate of top 3 common LHON mutations were 20.0%, which included 6 cases of ND4 11778 G to A, 1 case of ND1 3460 G to A. No ND6 14484 T to C mutation was detected. A ND4 G11719A synonymous mutation was found in all patients. In addition, 21 other mutations were discovered among 23 patients, among which 13 had a single mutation, 8 had a second mutations, and 2 had a third mutation. Among the 21 mutations, ND4 11778 G to A had a frequency of 28.6%(6/21). ND1 3552 T to A, ND6 14470 T to C, ND4 11794 T to C, ND1 3497 C to T and 3644 T to C respectively had a frequency of 19.0% (4/21), 19.0%(4/21), 14.3%(3/21), 9.5%(2/21) and 9.5%(2/21). Among the 3 patients who harbored a ND4 11794 T to C mutation, 2 were heteroplasmic and one was homoplasmic in nature.</p><p><b>CONCLUSION</b>The ND4 11778 G to A mutation is common in the Top "3" primary mutations of patients with LHON. Candidate LHON mutation ND1 3552 T to A or ND1 3644 T to C resulted in LHON pathogenesis as single or synergistic effect. The visual impairment at onset of the disease with candidate mutation were better than the eyes with the ND4 11778 G to A mutation.</p>

Detection of exon 7 mutations of PAH gene in classical phenylketonuria by high-resolution melting analysis / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To establish a simple, rapid, inexpensive and sensitive method for detecting hot region for mutations in exon 7 of PAH gene.</p><p><b>METHODS</b>High-resolution melting (HRM) technology was used to detect a c.728G>A mutation in exon 7 in 88 patients with classical type phenylketonuria. Suspected mutations were validated by direct DNA sequencing.</p><p><b>RESULTS</b>The results detected by HRM are in good agreement with the results obtained by direct sequencing.</p><p><b>CONCLUSION</b>HRM analysis is a simple, rapid, inexpensive and sensitive method for detecting hot mutational region in exon 7 of PAH gene.</p>

Study on the mutations of phenylalanine hydroxylase gene in patients with phenylketonuria in Shanxi province / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To study the mutations in exons 3, 6, 7, 11 and 12 of the phenylalanine hydroxylase gene (PAH) in Shanxi population.</p><p><b>METHODS</b>The mutations in exons 3, 6, 7, 11 and 12 and flanking sequences of PAH gene were detected by PCR-DNA sequencing, in 59 patients with phynelketonuria(PKU) and 100 healthy children from Shanxi province.</p><p><b>RESULTS</b>By sequence analysis, three single nucleotide polymorphism (SNP) Q232Q (CAA>CAG), V245V (GTG>GTA) and L385L (CTG>CTC) were detected in both the patients and healthy children, with the frequencies of nt 696, 735 and 1155 of the PAH cDNA up to 96.2%, 76.1% and 7.6% in patients respectively, and 97.0%, 77.3% and 8.3% respectively in the healthy controls. In addition, 72 different mutations accounting for 61.0% of mutant alleles were identified in the patients only. In exon 3, R111X, H64>TfsX9 and S70 del were found accounting for 5.1%, 0.8% and 0.8%; EX6-96A>G in exon 6 was found accounting for 10.2%. In exon 7, R243Q was the highest incidence accounting for 12.7%, followed by Ivs7+2 T>A(5.1%) and T278I(2.5%); the lowest incidences were G247V, R252Q, L255S, R261Q and E280K accounting for 0.8 %, respectively. In exon 11, Y356X (5.9%) and V399V (5.1%) were found; in exon 12, R413P and A434D were found accounting for 5.9% and 2.5%. In total, 9 missense mutations, 3 splice site mutations, 2 nonsense mutations and 2 deletions were included in 16 kinds of different mutations.</p><p><b>CONCLUSION</b>The mutation characteristics and distribution in exons 3, 6, 7, 11 and 12 of the PAH gene have been identified, and it suggested that the EX6-96A>G and R243Q were the hot spots of PAH gene mutations in Shanxi PKU population.</p>

Swallowing and laryngeal function preserving in surgical treatment of the head and neck tumors involving the tongue root / 中华耳鼻咽喉头颈外科杂志

<p><b>OBJECTIVE</b>To investigate the surgical technique which could preserve the swallowing and laryngeal function effectively in the malignant head and neck tumors involving the tongue root.</p><p><b>METHODS</b>From January 2003 to December 2008, 31 cases of malignant head and neck tumors involving the tongue base had been treated in this hospital were retrospectively analyzed. There were 27 males and 4 females in which 9 cases of primary malignant tumor were from the base of tongue; 3 cases were from the tonsil, 11 cases were from supraglottic laryngeal carcinoma and 8 cases were from hypopharyngeal carcinoma. Preserved the lingual artery of the reserved side and the normal tissue of the root of tongue according to the clinical anatomy of lingual artery during the operation. If preoperative CT had indicated that bilateral lingual arteries were involved, total glossectomy should have been done. The epiglottis, vocal cords and the ventricular band of larynx was preserved as much as possible for the mechanisms of laryngeal function.</p><p><b>RESULTS</b>In this group, residual tongue necrosis did not occurred. One case with total glossectomy didn't remove the trachea cannula. Five had total laryngectomy. The other 25 cases decannulated from 14th days to 90th days postoperatively. The time of oral feeding was started from 10th days to 31st days postoperatively. Two cases with hypopharyngeal carcinoma developed fistula, which were cured by dressing change. Two with root of tongue cancer and 1 with tonsil cancer had postoperative infection and healed in 2 weeks. The median follow-up time was 36 months, and the Kaplan-Meier 3-years and 5-years survival rates were 79.5% and 69.6% respectively.</p><p><b>CONCLUSIONS</b>In the surgical treatments of the malignant head and neck tumors involving the base of tongue, the excisions and reconstructions of the primary tumor and the involved tongue base according to the clinical anatomy of lingual artery and the protection mechanisms of laryngeal function during the operation was one of the most effective technique to preserve the swallowing and laryngeal function.</p>