Genetic analysis of a case of mild epilepsy due to variant of SCN9A gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic etiology of a patient with epilepsy and provide genetic counseling.@*METHODS@#A patient who had visited the Center for Reproductive Medicine of Shandong University on November 11, 2020 was selected as the study subject, and her clinic information was collected. Candidate variant was identified through whole exome sequencing (WES), and Sanger sequencing was used for validation. Possible transcriptional changes caused by the variant was detected by reverse transcription-PCR and Sanger sequencing.@*RESULTS@#The patient was a 35-year-old female with no fever at the onset, loss of consciousness and abnormal firing in the temporal lobe, manifesting predominantly as convulsions and fainting. WES revealed that she had harbored a heterozygous c.2841+5G>A variant of the SCN9A gene, which was verified by Sanger sequencing. cDNA sequencing confirmed that 154 bases were inserted between exons 16 and 17 of the SCN9A gene, which probably produced a truncated protein and affected the normal function of the SCN9A protein. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.2841+5G>A variant was classified as likely pathogenic (PVS1_Strong+PM2_Supporting).@*CONCLUSION@#The c.2841+5G>A variant of the SCN9A gene probably underlay the epilepsy in this patient. Above finding has enriched the variant spectrum of the SCN9A gene and provided a basis for the prenatal diagnosis and preimplantation genetic testing for this patient.

Identification of a novel variant of NHS gene underlying Nance-Horan syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Nance-Horan syndrome.@*METHODS@#Clinical manifestation of the patients was analyzed. Genomic DNA was extracted from peripheral blood samples of the pedigree members and 100 unrelated healthy controls. A panel of genes for congenital cataract was subjected to next-generation sequencing (NGS), and candidate variant was verified by Sanger sequencing and bioinformatic analysis based on guidelines of American College of Medical Genetics and Genomics (ACMG). mRNA expression was determined by reverse transcriptase-PCR (RT-PCR). Linkage analysis based on short tandem repeats was carried out to confirm the consanguinity.@*RESULTS@#A small insertional variant c.766dupC (p.Leu256Profs*21) of the NHS gene was identified in the proband and his affected mother, but not among unaffected members and the 100 healthy controls. The variant was unreported in Human Gene Mutation Database (HGMD) and other databases. Based on the ACMG guideline, the variant is predicted to be pathogenic (PVS1+PM2+PM6+PP4).@*CONCLUSION@#The novel variant c.766dupC of the NHS gene probably underlay the X-linked dominant Nance-Horan syndrome in this pedigree.

A case of tuberous sclerosis complex due to a novel splicing variant of TSC2 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a patient with tuberous sclerosis complex.@*METHODS@#Genomic DNA was extracted from peripheral blood samples from members of his family and 100 unrelated healthy controls. The proband was subjected to next-generation sequencing, and candidate variant was confirmed by multiple ligation-dependent probe amplification (MLPA) and Sanger sequencing. Reverse transcription-PCR (RT-PCR) was carried out to determine the relative mRNA expression in the proband.@*RESULTS@#The patient was found to harbor a c.2355+1G>C splicing variant of the TSC2 gene. Sequencing of cDNA confirmed that 62 bases have been inserted into the 3' end of exon 21, which has caused a frameshift producing a truncated protein.@*CONCLUSION@#The novel splicing variant c.2355+1G>C of the TSC2 gene probably underlay the TSC in the proband. Above finding has expanded the variant spectrum of TSC2 and provided a basis for preimplantation genetic testing and/or prenatal diagnosis.

Analysis of MECP2 gene variants in three pedigrees affected with Rett syndrome / 中华医学遗传学杂志

OBJECTIVE@#To detect potential variants of MECP2 gene in three pedigrees affected with Rett syndrome (RTT).@*METHODS@#All exons and their flanking regions of the MECP2 gene were subjected to Sanger sequencing and multiplex ligation-dependent probe amplification assay.@*RESULTS@#The probands of pedigrees 1 and 2 have respectively carried a c.965C>G and a c.1157_1197del41 variant of the MECP2 gene, while the proband of pedigree 3 carried a heterozygous deletional variant in exon 4 of the MECP2 gene.@*CONCLUSION@#Variants of the MECP2 gene probably underlay the RTT in the three pedigrees. Above finding has enriched the spectrum of MECP2 gene variants, and provided a guidance for the patients upon preimplantation genetic testing and prenatal diagnosis.

Identification of a novel splicing variant of IDS gene in a pedigree affected with type II glycosaminoglycan product storage disease / 中华医学遗传学杂志

OBJECTIVE@#To analyze variant of IDS gene in a pedigree affected with mucopolysaccharidosis type II (MPS II).@*METHODS@#The proband was subjected to next generation sequencing and Sanger sequencing to identify potential variants. Suspected variant was analyzed by its co-segregation with the disease in the pedigree. Its impact on mRNA splicing was analyzed by using reverse transcription PCR (RT-PCR).@*RESULTS@#A hemizygous IVS1-3T>G variant was found in the IDS gene in the proband. RT-PCR results revealed two abnormal cDNA fragments of 600 bp and 300 bp. The 600 bp fragment had inserted 216 nucleotides at the 3' end of intron 1, while the 300 bp fragment had lost 109 nucleotides at the 5' end of exon 2, which resulted in two truncated proteins comprising 38 and 92 amino acids, respectively, instead of the normal product (550 amino acids). The proband and his mother were respectively hemizygous and heterozygous for the variant. The same variant was not found among 100 normal controls.@*CONCLUSION@#The IVS1-3T>G variant of the IDS gene probably underlies the MPS II in this pedigree by causing reduction or elimination of the IDS protein.

Identification of a novel variant of COL4A5 gene in a pedigree affected with Alport syndrome / 中华医学遗传学杂志

OBJECTIVE@#To explore the genetic basis for a pedigree affected with Alport syndrome.@*METHODS@#Next generation sequencing and Sanger sequencing was carried out to detect potential variant of the COL4A5 gene among members from the pedigree and 100 unrelated healthy controls.@*RESULTS@#A novel missense c.3293G>T (p.Gly1098Val) variant was found in the COL4A5 gene among 6 affected members but not the unaffected members of the pedigree or the 100 healthy controls. According to the American College of Medical Genetics and Genomics standards and guidelines, the c.3293G>T variant was classified as pathogenic (PP1-strong+PM1+PM2+PP3+PP4).@*CONCLUSION@#By destructing the Gly-X-Y structure of its protein product, the c.3293G>T variant of the COL4A5 gene probably underlies the Alport syndrome in this pedigree. Above finding has enriched the spectrum of COL4A5 variants.

Novel mutations of XPC gene detected in a family affected with xeroderma pigmentosum group C / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect mutations of the XPC (XPC complex subunit, DNA damage recognition and repair factor) gene in a family affected with xeroderma pigmentosum group C (XP-C).</p><p><b>METHODS</b>The patient was subjected to next-generation sequencing and Sanger sequencing. Suspected mutations were validated by Sanger sequencing. Effect of splicing mutation was confirmed by reverse transcription-PCR (RT-PCR).</p><p><b>RESULTS</b>Compound heterozygous mutations of c.2098G to T and c.2034-7_2040del were found in the XPC gene in the proband. Among these, c.2098G to T (p.G700X) is a nonsense mutation resulting in a truncated XPC protein. C.2034-7_2040del involves the -1 position, which may alter the splice donor site of the intron 11 of XPC and result in a truncated XPC protein with loss of amino acids from 940 to 679 positions. The two mutations were not detected among 100 unrelated healthy controls.</p><p><b>CONCLUSION</b>Mutations of c.2098 G to T and c.2034-7_2040del of the XPC gene may lead to abnormal XPC expression and reduction or elimination of normal XPC functions, which may underlie the disease in this family.</p>

Observation on curative effects of astragalus injection(黄芪注射液) and Shenmai injection(参麦注射液) added during fever stage on hemorrhagic fever with renal syndrome / 中国中西医结合急救杂志

Objective:To study the influence of astragalus injection(黄芪注射液) plus Shenmai injection(参麦注射液) on each stage of hemorrhagic fever with renal syndrome(HFRS).Methods:Thirty-six cases with HFRS were randomly divided into treated group(n=19) which was treated with western medicine and traditional Chinese medicine (astragalus injection and Shenmai injection) and control group (n=17) which was treated with western medicine alone during fever stage.The curative effects were compared.Results:In treated group the rates of over hypotensive shock stage and over oliguria stage were both 94.74％ ,they were significantly heigher than those in control group(both P<0.05).The prolonged times of polyguria,increased blood urea nitrogen(BUN),and proteinuria in treated group were significantly shorter than those in control group (all P<0.01).Conclusions:The astragalus injection and Shenmai injection possess the ability to enhance the antidisease capability in patient with HFRS and are able to shorten the shock stage,to reduce the occurance rate of oliguria,to shorten the duration of each stage,and finally to shorten ill course and promote the patients to recovery as early as possible.