Syndromic Hirschsprung′s disease and its mode of inheritance / 中国当代儿科杂志

Hirschsprung′s disease (HSCR) is one of the major causes of chronic incomplete intestinal obstruction in children. HSCR is considered a type of neurocristopathy caused by no colonization of ganglion cells on some parts of the bowel wall due to abnormal termination of the migration of vagal neural cells during embryonic development. This disease can be classified into different types according to the length of the affected intestinal canal. Most HSCR patients present with single deformity, but some HSCR patients are affected by other deformities, which constitutes syndromic HSCR, such as congenital central hypoventilation syndrome, Fryns syndrome, and cartilage-hair hypoplasia syndrome. Most syndromes have abnormal genetic material. An adequate knowledge of syndromic HSCR is of vital importance for accurate diagnosis and prognostic evaluation. This article reviews the clinical manifestations, genetic basis, and genetic modes of different types of syndromic HSCR.

Mutation analysis of methyl CpG-binding protein 2 gene(exon 3) in Hirschsprung disease and anorectal malformations / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To explore the relationship between exon 3 mutation in the methyl CpG-binding protein 2 (MeCP2-E3) gene and Hirschsprung disease (HSCR) and anorectal malformations (ARMs).</p><p><b>METHODS</b>PCR and DNA sequencing were used to detect the mutation of MeCP2-E3 in 120 healthy controls, 120 HSCR, and 50 ARMs.</p><p><b>RESULTS</b>On sequencing, 45(37.5%) children with HSCR had basic replacement in MeCP2-E3, 12(10.0%) of them were homozygous mutation. Fourteen(28.0%) children with ARMs had basic replacement in MeCP2-E3, 4(8%) of them were homozygous mutation. There were no mutation in the control group.</p><p><b>CONCLUSIONS</b>Mutation of MeCP2-E3 is present in the peripheral blood of children with HSCR or ARMs, which may contribute to the development of Hirschsprung disease or anorectal malformations.</p>

Mutation and expression of WNT8b gene and SHH gene in Hirschsprung disease / 中华胃肠外科杂志

<p><b>OBJECTIVE</b>To investigate the relationship of WNT8b and SHH genes mutation and Hirschsprung disease(HSCR) in Chinese children.</p><p><b>METHODS</b>Preoperative whole blood preparations in 72 children with sporadic HSCR from northeast China were collected(study group). Seventy-two healthy children were used as controls(matched for sex and age). Genomic DNA was obtained from peripheral blood. Exon 1 of WNT8b gene and the exon 1 of SHH gene were analyzed for gene mutation. The mutation products were automatically sequenced. The levels of WNT8b and SHH mRNA were detected by quantitative real-time PCR(qRT-PCR) in blood samples.</p><p><b>RESULTS</b>On sequencing, 13 out of 72 children with HSCR had WNT8b gene mutation in the coding area, including heterozygosity deletion in 8 cases (11.1%) and base replacement in 5(6.9%). Eleven children with HSCR had SHH gene mutation in the coding area including heterozygosity deletion in 7 cases(9.7%) and base replacement in 4(5.6%). No mutations in WNT8b and SHH genes were found in the control group. The WNT8b and SHH mRNA levels were different between the study group and the control group(30.01±1.13 vs. 17.33±0.62, and 28.25±1.27 vs. 18.94±0.31, P<0.05).</p><p><b>CONCLUSIONS</b>WNT8b and SHH mutations and abnormal expressions are present in the peripheral blood of children with sporadic HSCR. These two genes may be related to the development of sporadic HSCR in children in the northeastern China.</p>

Cell apoptosis during the cloacal embryonic development in rats with anorectal malformations / 中国当代儿科杂志

<p><b>OBJECTIVE</b>In the normal embryonic development of anorectum, apoptosis plays an important role. To explore the role of apoptosis in anorectal malformations (ARM), this study investigated cell apoptosis during the cloacal embryonic development in ARM embryos.</p><p><b>METHODS</b>ARM embryos were induced by intragastric administration of ethylenethiourea (125 mg/kg) for pregnant rats on embryonic day 10 (E10). The distribution of apoptotic cells in the cloaca was ascertained by hematoxylin and eosin and TUNEL staining in the normal control embryos (n=102) and ARM embryos (n=147) on E13, E13.5, E14, E15 and E16.</p><p><b>RESULTS</b>On E13, apoptotic cells were detected in the urorectal septum of rat embryos in the control group. With the development of embryos, the number of apoptotic cells in the mesenchyme of urorectal septum gradually increased and a large number of apoptotic cells were seen in the dorsal rectal mesenchyme. On E14, apoptotic cells appeared at the terminal rectum and the dorsal cloacal membrane. On E15, the urorectal septum fused with the cloacal membrane and apoptotic cells in the urorectal septum mesenchyme continuously extended down to the fusion region. Compared with the control group, apoptotic cells in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane of the ARM rat embryos were significantly reduced during the embryonic development. The development of the urorectal septum was delayed and it did not fuse with the cloacal membrane in ARM embryos.</p><p><b>CONCLUSIONS</b>During the embryonic development of cloaca, abnormal apoptosis in the urorectal septum, the dorsal rectal mesenchyme and the cloacal membrane may be one of the reasons for anorectal malformations. The proper regulation of cell apoptosis may be one of the key mechanisms for normal development of anorectum in the embryonic stage.</p>

Coding-sequence point mutation and polymorphism analyses of SIP1 gene in Hirschsprung disease / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the point mutations and polymorphisms of SIP1 gene in Hirschsprung disease(HSCR) and discuss the relationship between the feature of gene mutations and single nucleotide polymorphisms of SIP1 gene and HSCR.</p><p><b>METHODS</b>Polymerase chain reaction-single strand conformation polymorphism(PCR-SSCP)and DNA direct sequencing were performed in 50 HSCR cases and 30 normal controls. All 10 exons of SIP1 gene were analyzed for point mutations and single nucleotide polymorphisms (SNPs).</p><p><b>RESULTS</b>Loss of heterozygosity was observed in exon 7 in one patient. This variation leads to a nonsense mutation (L157L) and is an SNP. A missense mutation was detected in exon 8 in four patients, the frequency was 8%(4/50). PCR-SSCP was analyzed by silver staining. Identical patterns were observed in exon 2 for two cases, exon 7 for three cases, and exon 8 in seven patients.</p><p><b>CONCLUSION</b>The mutations of SIP1 gene were detected in HSCR. The results suggest that SIP1 gene might play an important role in the pathogenesis of HSCR.</p>

Expression of fusion gene PAX3/PAX7-FKHR and chromosomal aberration in rhabdomyosarcoma / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the PAX3/PAX7-FKHR fusion transcripts to identify genetic alteration in embryonal rhabdomyosarcoma (ERMS) and alveolar rhabdomyosarcoma (ARMS) tissues.</p><p><b>METHODS</b>One-step reverse transcription- polymerase chain reaction (RT-PCR) were used to detect the expression of the PAX3/PAX7-FKHR fusion transcrips in 16 cases of rhabdomyosarcoma (7 cases of ARMS, 9 cases of ERMS) and 16 specimens were compared to the surrounding normal tissue. Comparative genomic hybridization (CGH) was employed to detect the genomic imbalance (DNA loss or amplification) in 16 RMS cases.</p><p><b>RESULTS</b>PAX3-FKHR fusion transcripts were positive in 3/7 and PAX 7-FKHR fusion transcripts were positive in 2/7 of ARMS patients, respectively, and were all negative in ERMS and Control tumors. There were different chromosome variations for each RMS, chromosome amplification was frequently seen in 1p36 (69%), 5q32 (56%), 8q21 (63%), 13q14 (69%), 19q (63%), 20q (56%). Chromosome loss was frequently seen in 3p21-pter (56%), 9p23-pter (50%), 10q (69%), 16/16q24 (56%).</p><p><b>CONCLUSION</b>One-step RT-PCR assay for detection specific fusion gene provides a useful tool for confirmation of the diagnosis of RMS in diagnostically difficult cases and in retrospective studies. Chimeric gene transcript resulting from specific chromosomal translocations is a reliable index for the molecular diagnosis of RMS.</p>

Genomic imbalance and chromosome disorders in hepatoblastoma / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To establish stable techniques of comparative genomic hybridization (CGH) and apply them to elucidate the genetic characteristics of hepatoblastoma (HB), and to explore the characteristics and clinical significance of loss of heterozygosity (LOH) at 1p36 in HB.</p><p><b>METHODS</b>CGH was employed to detect the genomic imbalance (DNA loss or amplification) in 20 cases of HB, and PCR-simple repeated sequence polymorphism was employed in 30 cases of HB to detect the loss of heterozygosity for 6 satellites at chromosome 1p36.</p><p><b>RESULTS</b>There were different chromosome variations for each HB. chromosome amplification was frequently seen in 1q, 2q,2p, 8q, 8p, 12q and 22q. Chromosome loss was often seen in 1p, 4q, 4p, 16q, 17p and 18q. The frequency of LOH at 6 loci on chromosome 1 was 63.3% totally (19/30), with the highest D1S199 (66.7%) and D1S450 next to it (46.7%).</p><p><b>CONCLUSION</b>There were chromosome zones with DNA amplification or loss in hepatoblastoma. There are extensive LOH at 1p36 in hepatoblastoma. The corresponding amplification of oncogene and loss of antioncogene may take part in the development of hepatoblastoma.</p>

Speech therapy and occupational therapy on Broca aphasia with bucco-facial-apraxia following hemiplegia after stroke / 中国康复理论与实践

@#ObjectiveTo study the method about language rehabilitation for Broca aphasis with bucco-facial apraxia in hemiplebies after stroke.Methods55 patients in hemiplegies after stroke who were diagnoised Broca aphasia with bucco-facial-apraxia by Chinese standard language test of aphasia and apraxia test,were randomly divided into two groups:treatment group(30 cases) and control group(25 cases). The trainning about language rehabilitation and occupational therapy(OT)to bucco-facial-apraxia were given in the treatment group, while in the control group the language rehabilitation training were given only. Evaluation was done in pre-treatment and post-treatment respectively.ResultsThe improvement of bucco-facial-apraxia and language expression function(repetition,speech and speech-reading) of treatment group were significant than that of control group (P<0.05).Conclusions The OT for bucco-facial-apraxia may obviously improved bucco-facial-apraxia and language expression function on training of language rehabilitation for Broca aphasia with bucco-facial-apraxia.