Glaucoma and amyotrophic lateral sclerosis,two kindred diseases?

Amyotrophic lateral sclerosis （ALS）, a predominantly sporadic disease with unknown etiology and pathogeny, is a member of a group known as motor neuron diseases （MND）. The heterogeneity of the clinical presentation of the disease is a fundamental aspect of ALS and is de- termined by the variable engagement of its upper motor neuron （UMN） and lower motor neuron （LMN） components （Ravits and La Spada, 2009）.

A novel nonsense mutation of GPR143 gene in a Korean kindred with X-linked congenital nystagmus

Dear Editor,I am Dr.Ungsoo Samuel Kim.from Kim＇s Eye Hospital,Konyang University,Seoul,Korea.I write to present a novel mutation of GPR143 in Korean patients with X-linked congenital nystagmus by using exome sequencing.Congenital nystagmus is an inherited ocular disorder that can occur as an X-linked condition.

Screening analysis of candidate gene mutations in a kindred with polycystic liver disease

AIM:To find potential mutable sites by detecting mutations of the candidate gene in a kindred with polycystic liver disease(PCLD).METHODS:First,we chose a kindred with PCLD and obtained five venous blood samples of this kindred after the family members signed the informed consent form.In the kindred two cases were diagnosed with PCLD,and the left three cases were normal individuals.All the blood samples were preserved at-85?℃.Second,we extracted the genomic DNA from the venous blood samples of the kindred using a QIAamp DNA Mini Kit and then performed long-range polymerase chain reaction(PCR)with different primers.The exons of PKD1 were all sequenced with the forward and reverse primers to ensure the accuracy of the results.Next,we purified the PCR products and directly sequenced them using Big Dye Terminator Chemistry version 3.1.The sequencing reaction was conducted with Biomek FX(Beckman).Finally,we analyzed the results.RESULTS:A total of 42 normal exons were identified in detecting mutations of the PKD1 gene.A synonymous mutation occurred in exon 5.The mutation was a homozygous T in the proband and was C in the reference sequence.This mutation was located in the third codon and did not change the amino acid encoded by the codon.Missense mutations occurred in exons 11 and 35.These mutations were located in the second codon;they changed the amino acid sequence and existed in the db SNP library.A nonsense mutation occurred in exon 15.The mutation was a heterozygous CT in the proband and was C in the referencesequence.This mutation was located in the first codon and resulted in a termination codon.This mutation had an obvious influence on the encoded protein and changed the length of the protein from 4303 to 2246amino acids.This was a new mutation that was not present in the db SNP library.CONCLUSION:The nonsense mutation of exon 15existed in the proband and in the third individual.Additionally,the proband was heterozygous for this mutation,so the mutable site was a pathogenic mutation.

HMLH1 gene mutation in gastric cancer patients and their kindred

AIM: To study the status of hMLH1 gene point mutations of gastric cancer kindreds and gastric cancer patients from northern China, and to find out gene mutation status in the population susceptible to gastric cancer. METHODS: Blood samples of 120 members from five gastric cancer families, 56 sporadic gastric cancer patients and control individuals were collected. After DNA extraction,the mutations of exon 8 and exon 12 of hMLH1 gene were investigated by PCR-SSCP-CE, followed by DNA sequencing.RESULTS: In the five kindreds, the mutation frequency was 25% (5/16) for the probands and 18% (19/104) for the non-cancerous members, which were significantly higher than the controls (P＜0.01 x2 = 7.71, P＜0.01 x2 = 8.65, respectively). In the sporadic gastric cancer, the mutation frequency was 7% (4/56), which was similar to that (5/100) in the healthy controls. The mutation point of exon 8 was at 219 codon of hMLH1 gene (A-G), resulting in a substitution of Ile-Val (ATC-GTC), whereas the mutation of exon 12 was at 384 codon of hMLH1 gene (T-A) resulting in a substitution of Asp-Val (GTT-GAT), which were the same as previously found in hereditary nonpolyposis colorectal carcinoma.CONCLUSION: The members of gastric cancer families from northern China may have similar genetic background of hMLH1 gene mutation as those of hereditary nonpolyposis colorectal carcinoma.