hMLH1 Gene Mutations Research Articles

Biography: Mutated hMLH1 Gene in Bangladeshi Gastric Cancer Patients: Its Relevance to Clinicopathological Factors

Like all cancers, Gastric cancer (GC) is also known to be of genetic origin. Genes are mutated in every steps of cell division, among them hMLH1 is a DNA mismatch gene which plays important role during carcinogenesis. This study was chalked out to find out the status of mutated hMLH1 Gene and its clinicopathological relevance among Bangladeshi gastric cancer patients. It was a cross sectional study conducted during January 2015 to April 2016. Tissue extracted from gastrectomy specimen of carcinoma stomach patients sent to specified laboratory. In the laboratory after DNA extraction, PCR, sequencing and analysis was done. In this study out of 19, exons 7 and 8 and introns 8 and 9 were studied after primer designing for hMLH1 gene mutation. After analysis, mutated gene were matched with clinicopathological parameters like age, sex, location of tumour, types and grade of tumour to see their relevance. Out of 45 patients, mutation was found in 15 patients (33.3%). Most gene alteration was found in elderly patients, more in male. Antral growth had more (80.0%) mutation and in ulceroproliferative type (66.7%) (p < .005). Mutation was common in intestinal type (73.3%) of GC. hMLH1 gene mutation found more in the moderately differentiated carcinoma patients. Factors like age, sex, morphology, Lauren’s type, grading, personal habits etc. might play pivotal role in the development of gene mutation. Multi-centre large study are required to extract more relevant information in this regard.

Pushing the haystack aside for efficient gene targeting in human cells.

Gene targeting, i.e., the disruption of a specific gene via homologous recombination, is one of the key techniques to study gene function. However, researchers have faced the difficulty that, in human cells, the frequency of correct targeted integration is quite low compared to non-targeted (or random) integration. Adachi and colleagues investigated the factors that influence the ratio of targeted integration to non-targeted integration.

Double heterozygosity for BRCA1 and hMLH1 gene mutations in a 46-year-old woman with five primary tumors

Germline mutations in BRCA1 and BRCA2 genes predispose to hereditary breast cancer, whereas carriers of mutations in any of the mismatch repair genes (MMR; hMLH1, hMSH2, hMSH6, hPMS2) are highly susceptible to Lynch syndrome. In the present study, we describe a woman affected by unilateral breast cancer at the age of 35years. After 4years, during the follow-up she developed synchronous (and asymptomatic) endometrial cancer, ovarian carcinoma and renal clear cell carcinoma. After 7years (at age 46), the patient developed an infiltrating carcinoma of the contralateral breast and died in a few months of metastatic disease. Initial investigations led to the detection of a constitutional mutation in the BRCA1 gene. The extended genealogical tree disclosed a suspected history of colorectal carcinoma in the maternal branch. Endometrial cancer of the proband was investigated for microsatellite instability (MSI) and immunohistochemical expression of MLH1, MSH2 and MSH6 proteins. An high MSI status and lack of expression of MLH1 protein were detected. hMLH1 gene sequencing revealed the presence of a constitutional mutation, which was also found in the mother of the proband. Loss of the wild-type hMLH1 allele was detected in both breast tumors, thus suggesting that the MMR defect contributed to the development of the breast cancer.

Two novel mutations in hMLH1 gene in Iranian hereditary non-polyposis colorectal cancer patients

Hereditary non-polyposis colorectal cancer (HNPCC) is one of the most common forms of hereditary colorectal cancer. It is an autosomal dominant disorder resulting from germline mutations in DNA mismatch repair genes. In this study, we screened hMLH1 gene in a group of Iranian HNPCC patients using polymerase chain reaction-single strand conformational polymorphism and direct sequencing methods. Here we report two novel frameshift mutations in this gene in our studied population. One of them results from a deletion of "T" at codon 36, exon 1 which causes premature stop codon and a truncated protein. The other results from a deletion of "T" at codon 753, exon 19 causing a delayed stop codon. There are a variety of the reported novel mutations in hMLH1 gene studies. Identification of these mutations is necessary in different populations and can help the management of colorectal cancer in these populations by screening, by prevention strategies, and by following up the suspected HNPCC families.

The relationship between human muth homolog 1 gene mutation at site 415 and sporadic colon cancers in Chinese Han population

Abstract Background: The genetic factors of colon cancer play an important role in the tumor development and growth. The incidence of colon cancers has greatly increased in China. However, few data is available for the relationship between human muth homolog 1 (hMLH1) gene mutation at site 415 and sporadic colon cancers in Chinese population. Objective: Investigate the relationship between G→C mutation in hMLH1 gene at site 415 and sporadic colon cancers in Chinese Han population. Methods: Using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and DNA sequencing techniques, the genotype of the hMLH1 gene was analyzed at site 415 in 97 cases of sporadic colon cancer patients and 138 controls. Reverse-transcription (RT)-PCR was used to determine the level of hMLH1 mRNA expression in normal colonic mucosa of patients with different genotype. Results: The frequency of genotype C/C at the 415 site of the hMLH1 gene was significantly higher in colon cancer patients than in controls. The expression levels of hMLH1 mRNA in normal colonic mucosa were similar in colon cancer patients with different genotypes. Conclusion: G’!C mutation in hMLH1 gene at site 415 may represent a genetic factor that is associated with sporadic colon cancer in a small group of Chinese Han population.

HMLH1 and hMSH2 gene mutations in a population susceptible to gastric cancer

hMLH1 and hMSH2 gene mutations in a population susceptible to gastric cancer

Serous oligocystic adenoma (SOIA) of the pancreas – first reported case of a genetically fixed association in a patient with hereditary non-polyposis colorectal cancer (HNPCC)

Cystic tumor lesions of the pancreas are relatively uncommon. Advances in imaging and pathohistology, including immunohistochemistry, have led to the detection and classification of novel tumor entities. A promoting aspect is the extended indication profile in pancreatic surgery, in particular, because of lower perioperative morbidity and mortality. One of these classified cystic neoplasms of the pancreas is serous oligocystic adenoma (SOIA), a rare and benign tumor lesion. We report on a 41-year-old man with a cystic lesion within the pancreatic head. Therefore, he underwent pylorus-preserving cephal duodenopancreatectomy. Pathohistologic investigation revealed a SOIA. He had a medical history significant for subtotal colectomy because of a synchronous double colonic carcinoma. Both tumor tissue specimens had been characterized for a high level of microsatellite instability (MSI) and loss of hMLH1, as well as for a corresponding germ line mutation in hMLH1 gene, leading to the diagnosis of hereditary non-polyposis associated colon cancer (HNPCC). The case is remarkable since the SOIA revealed MSI and loss of hMLH1 protein in the tumor cells that has never been reported for this tumor type. In addition, there is a rare and extraordinary association between SOIA and HNPCC, which has never been published before, since SOIA, in this case, could have been developed in the setting of HNPCC syndrome.

Analysis of a correlation between the BRAF V600E mutation and abnormal DNA mismatch repair in patients with sporadic endometrial cancer

Point mutations of KRAS and BRAF genes are thought to be important in carcinogenesis of colon cancer. In particular, gene instability caused by decreased expression of the hMLH1 gene, a DNA mismatch repair (MMR) gene, may be linked to the activating BRAF V600E point mutation in sporadic colon cancer. However, a consensus has not been established regarding the correlation between point mutations of KRAS or BRAF and carcinogenesis in patients with endometrial cancer, which is closely related to colon cancer. Therefore, we analyzed aberrant hypermethylation of the hMLH1 gene, microsatellite instability (MSI), and point mutations of KRAS and BRAF in 44 samples of sporadic endo-metrial cancer, with the aim of examining the mechanism of carcinogenesis in patients with endometrial cancer. Aberrant hMLH1 hypermethylation was found in 17 of the 44 cases (38.6%) and showed a significant positive correlation with MSI (p=0.02). This suggests that an abnormal MMR mechanism plays an important role in carcinogenesis of sporadic endometrial cancer. Point mutation of KRAS was found in 6 of the 44 cases (13.6%), but no BRAF V600E mutation was detected. These data suggest that the BRAF V600E mutation is not the target gene for abnormal MMR in carcinogenesis in patients with sporadic endometrial cancer, unlike in colon cancer. This is supported by the relatively few previous reports indicating a correlation between endometrial cancer and the BRAF V600E mutation. Identification of new candidates for the target gene for abnormal MMR in endometrial cancer requires further work.

Comparison of the sensibility and specificity between single-stranded conformation polymorphism and denaturing high-performance liquid chromatography in screening hMSH2 and hMLH1 gene mutations in hereditary non-polyposis colorectal cancer

To compare the sensibility and specificity between single-stranded conformation polymorphism (SSCP) and denaturing high-performance liquid chromatography (DHPLC) in screening hMSH2 and hMLH1 gene mutations for the diagnosis of hereditary non-polyposis colorectal cancer (HNPCC). Seven Chinese HNPCC kindreds were collected. PCR-SSCP and DHPLC were used to screen the coding regions of hMSH2 and hMLH1 genes and the abnormal profiles were sequenced by a 377 DNA sequencer. Seven gene sequence variations of hMSH2 or hMLH1 were found. Among them, 4 variations were not found by SSCP, but by DHPLC. The sensibility of SSCP and DHPLC were 51.6% and 100% respectively, and the specificity were 66.6% and 93.3% respectively. DHPLC has better sensibility and specificity in screening hMSH2 and hMLH1 gene mutation as compared to SSCP. DHPLC is an ideal method in the diagnosis of HNPCC.

Clinical features and hMSH2/hMLH1 germ-line mutations in Chinese patients with hereditary nonpolyposis colorectal cancer

At least five mismatch repair (MMR) genes, including hMSH2, hMLH1, hPMS, hPMS2, and hMSH6/GTBP, are associated with hereditary nonpolyposis colorectal cancer (HNPCC). More than 90% of families with HNPCC harbor the hMSH2 and hMLH1 gene mutations. We have analyzed the clinical features of HNPCC among Chinese patients and report the results of screening for mutations in the hMSH2 and hMLH1 genes. The data concerning gender, site of colorectal cancer (CRC), age at diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors for 126 patients from 28 independent families with HNPCC were collected. Fifteen of the families met the Amsterdam I criteria, and 13 met the Japanese clinical criteria for diagnosis. Genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of the hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced. One hundred and seventy malignant neoplasms were found in the 126 patients, of whom 23 had multiple cancers. Ninety-eight of the patients (77.8%) had colorectal cancers, with an average age at onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germ-line G204X nonsense mutation in the third exon of hMSH2 was found, representing the first mutation in an MMR gene ever found in people of Chinese Mongolian ethnicity. HNPCC is a typical autosomally dominant hereditary disease, characterized by early onset, a predominance of proximal colorectal cancer, and multiple synchronous and metachronous colorectal cancers. DHPLC is a powerful tool for detecting mutations in the hMSH2 and hMLH1 genes. Mutations in the first nine exons of the hMLH1 gene were more common in Chinese patients.

A novel mutation in hMLH1 gene in a Uruguayan Hereditary non-polyposis colorectal cancer (HNPCC-Lynch syndrome) family

22203 Background: HNPCC is the most common colorectal cancer syndrome and is associated with germ-line mutations in DNA mismatch repair genes (MMR). To date, more than 700 MMR gene mutations have been identified. The MMR gene mutation spectrum may vary across different populations and be influenced by founder mutations that prevail in specific ethnic groups. Uruguay is a small country without considerable genetic diversity and whose population is mainly originated from Southern Europe. We have previously reported an unexpectedly low frequency of molecularly defined HNPCC cases despite advanced methodology used for mutation detection, which may suggest the involvement of novel susceptibility genes. Methods: Ten Amsterdam positive families, seven of them without microsatellite instability (MSI) in their proband´s tumours, where thoroughly evaluated for mutations in hMLH1 and hMSH2 by Single-Strand Conformation Polymorphism (SSCP) and direct sequencing of genomic DNA from peripheral blood performed in the proband. Results: We identified a novel hMLH1 mutation (c.289T>G - Y97D) in a 37 year-old colorectal cancer patient from a family with eleven affected members, Amsterdam I positive criteria and without MSI. The affected family members are descendant of a Spanish family and the mean colon cancer diagnosis was 54 years old. This mutation has not been reported to the available databases (InSiGHT or the Newfoundland database). Conclusions: We identified a novel punctual germ-line mutation in hMLH1 in an HNPCC patient with microsatellite stable colorectal cancer. Absence of MSI in HNPCC patients is found only in 10–15% of cases. Southern Europe people represent mixed populations in which no particular mutation has been enriched and therefore it is not surprising that Uruguayan mutations differ from those found in Southern Europeans. However, novel mutations and the reported unexpectedly low frequency of molecularly defined HNPCC cases can be explained by a different mutational spectrum in the Uruguayan population which should be further investigated. No significant financial relationships to disclose.

Novel hMSH2, hMSH6 and hMLH1 gene mutations and microsatellite instability in sporadic colorectal cancer

To detect the hMSH2, hMSH6 and hMLH1 DNA mismatch repair gene mutations and microsatellite instability in somatic colorectal cancer. The mutations of hMSH2, hMSH6, and hMLH1 genes, including microsatellite instability of BAT-26, BAT-40, D2S123, D5S346 and D17S250 were analyzed in 31 patients with colorectal. The results revealed that eight cases (25.8%) harbored mutations in DNA mismatch repair genes. Of these, five novel mutations including I237V in exon 4 of hMSH2, ins T at codon 1196 in exon 7 of hMSH6, and ins G at codon 154 in exon 6, N158H in exon 6, and del A at codon 257 in exon 9 of hMLH1 were identified. Moreover, several intronic polymorphisms, including c-g transversion at IVS-1 nt211 + 9 of hMSH2, del T in poly T track at IVS-6 nt3559-5, ATCT duplicate in IVS-7 nt 3642 + 35 and t-g transversion at IVS-10 nt4080 + 185 of hMSH6 were demonstrated in these patients. In addition, seven cases (22.5%) exhibited microsatellite instability (MSI). These results suggested that the inactivation of DNA mismatch repair genes and microsatellite instability may play a minor role in somatic colorectal cancer development.

HMLH1 gene mutation in gastric cancer patients and their kindred

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. 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. 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 chi2 = 7.71, P<0.01 chi2 = 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. 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.

Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients

To analyze the clinical features of hereditary nonpolyposis colorectal cancer (HNPCC) among Chinese and report the results of screening of hMSH2 and hMLH1 gene mutations. The data concerning sex, site of colorectal cancer (CRC), age of diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors of 126 patients from 28 independent families of HNPCC in China were collected, of which 15 met the Amsterdam criteriaI and 13 met the Japanese clinical diagnosis criteria. The genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer. One hundred and seventy malignant neoplasms were found in the 126 patients, in which 23 of multiple cancers were found. Ninety-eight of the 126 patients (77.8%) had colorectal cancers, with an average age of onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germline G204X nonsense mutation in the third exon of hMSH2 was found for the first time, the first mismatch repair gene (MMR) mutation ever found in Chinese Mongolian people. HNPCC is a typical auto-dominant hereditary disease, characterized by early onset, proximal predominance of colorectal cancer, multiple synchronous and metachronous colorectal cancers, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous colorectal cancers are notable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening. Three novel mutations have been found. hMLH1 gene mutations, especially those of the first nine exons, are more common than hMSH2 gene mutations in Chinese patients.

Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma.

Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly-inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations. Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC), age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer. One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twenty-seven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had metachronous CRCs within 10 years after operation. Eight hMSH2 or hMLH1 gene sequence variations were found in twelve families, including the first Mongolian kindred with a hMSH2 gene mutation. HNPCC is characterized by an early-age onset, proximal predominance of CRC, multiple metachronous CRCs, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous CRCs are the remarkable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening. hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients. Three of seven mutations have been found to be novel, and the germline G204X nonsense mutation in the third exon of hMSH2 has become the first MMR gene mutation found in Chinese Mongolian people.

HMLH1 and hMSH2 gene mutations are present in radial growth‐phase cutaneous malignant melanoma cell lines and can be induced further by ultraviolet‐B irradiation

Microsatellite instability and reduced expression of mismatch repair proteins were reported in melanomas. However, little is known about mutational changes of the mismatch repair genes in radial growth-phase melanoma especially following UVB irradiation. To investigate these changes, an in vitro system consisting of radial growth-phase Wistar melanoma cell lines (WM35, WM3211 and WM1650) was established. The cells were UVB irradiated (10 mJ/cm(2)), and evaluated for mutational changes of exon regions 13,16 and 19 (hMLH1) and 6,7 and 12 (hMLH2) of these genes before and after irradiation. The genomic DNAs were PCR amplified and the products were directly sequenced. Transition (C-->T, G-->A, T-->C) and transversion (G-->, A-->T) mutations were found in exons 6,16 and 19. Some were present in both the sham-irradiated and UV-irradiated cells but others were only detected after UVB irradiation. hMLH1 and hMLH2 gene mutations occur early in melanoma tumorigenesis. The ability of UVB irradiation to induce additional mutations in these repair genes suggests its possible role in melanoma pathogenesis. Further investigation will be needed to determine whether mutations such as these contribute to the development of microsatellite instability in melanoma.

Infrequent microsatellite instability in liver fluke infection-associated intrahepatic cholangiocarcinomas from Thailand.

The liver fluke infection-associated intrahepatic cholangiocarcinoma (ICC) is a major liver cancer in Northeast Thailand. The molecular basis of this ICC is poorly understood. To address possible roles of the DNA mismatch repair (MMR) system in ICC carcinogenesis, a fluorescence-labeling PCR/laser scanning technique with high sensitivity was employed to analyze genomic instability in the nuclear DNA (nDNA) and mitochondrial DNA (mtDNA) in 24 fresh and 13 formalin-fixed, paraffin-embedded tissues of ICC and their corresponding normal parts. Microsatellite instability (MSI) was assessed in nDNA, using 12 highly polymorphic loci including 5 Bethesda markers. These loci were mainly related to major MMR genes, hMSH2 and hMLH1. Also 3 (C)n and/or (C)n(A)n repeat instability at 1 noncoding region in the displacement-loop (D-loop) and 2 coding sequences in NADH dehydrogenase subunit 1 and subunit 5 gene in mtDNA were analyzed. MSI was only detected in 1 (2.7%), 6 (16.7%), 1 (2.9%), 1 (2.9%) or 2 (6.3%) out of 37, 36, 35, 35 or 32 cases at BAT-25, D2S123, D3S1611, D11S904 or D17S250, respectively. LOH was found at D3S1298, D3S1561, D5S346 and TP53 in 4 (18.2%) out of 22, 2 (18.2%) out of 11, 6 (33.3%) out of 18 and 3 (12.5%) out of 24 informative cases, respectively. In mtDNA, none except a single case out of the 37 (2.7%) exhibited repeat sequence instability in the D-loop. We conclude that the liver fluke infection-associated ICC in Thailand is classified as low frequency MSI or microsatellite stable type and that DNA MMR system, through hMSH2 and hMLH1 gene mutations, does not play a major role in its carcinogenesis.

A single-strand conformation polymorphism method by capillary electrophoresis with laser-induced fluorescence for detection of the T1151A mutation in hMLH1 gene.

Mutation of hMLH1 gene plays an important role in human tumorigenesis. A highly sensitive single-strand conformation polymorphism (SSCP) method for detection of the T1151A mutation in exon 12 of the hMLH1 gene was for the first time developed employing laser-induced fluorescence capillary electrophoresis (LIF-CE). Effects of the concentration of linear polyacrylamide solution, running temperature, running voltage and the addition of glycerol on SSCP analysis were investigated, and the optimum separation conditions were defined. Thirty colorectal cancer patients and eight lung cancer patients were screened and the T1151A mutation was found in four of them. Based on CE-sequencing the mutation was further confirmed. To our knowledge, this is for the first time that the T1151A mutation is found in lung cancer. Our method is simple, rapid, and highly sensitive and is well suited to the analysis of large numbers of clinical samples.

Electro-Oculographic and Electroretinographic Studies in HNPCC Gene Mutation Carriers

Purpose: To assess retinal function in HNPCC gene mutation carriers. Patients: 19 carriers (38 eyes) of HNPCC genes and controls. Methods: Electro-oculogram, standard flash electroretinogram and pattern electroretinogram (PERG) recordings were performed. Results: In the total group of HNPCC gene mutation carriers examined by oscillatory potentials, reduced amplitude (p < 0.0004) and increased latency (p < 0.04) of the O3 wave and increased latency (p < 0.02) of the O4 wave were found. In the subgroup of carriers with hMLH1 gene mutation, reduced amplitudes of the O3 (p < 0.0005) and O4 (p < 0.04) waves were identified. In the total group of HNPCC gene mutation carriers examined by PERG, reduced amplitudes of the P50 (p < 0.003), N95 (p < 0.02) and abnormal N95/P50 ratio (p < 0.02) were revealed. In the subgroup of hMLH1 gene mutation carriers, reduced amplitude of the P50 (p < 0.04) and abnormal N95/P50 ratio (p < 0.02) were observed, whereas in the hMSH2 gene mutation carrier subgroup, reduced amplitude (p < 0.03), shortened latency of the P50 wave (p < 0.02) and reduced amplitude of the N95 wave (p < 0.03) were found. Conclusion: Constitutional dysfunction of the inner retina appears to be a characteristic feature of HNPCC gene mutation carriers.

HMLH1 and hMSH2 Gene Mutation in Brazilian Families With Suspected Hereditary Nonpolyposis Colorectal Cancer

hMLH1 and hMSH2 Gene Mutation in Brazilian Families With Suspected Hereditary Nonpolyposis Colorectal Cancer