Ponatinib inhibits growth of patient-derived xenograft of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein in nude mice / 南方医科大学学报

OBJECTIVE@#To investigate the antitumor effect of ponatinib on the growth of cholangiocarcinoma xenograft derived from a clinical patient in a mouse model expressing FGFR2-CCDC6 fusion protein.@*METHODS@#Lung metastatic tumor tissue was collected from a patient with advanced intrahepatic cholangiocarcinoma and implanted subcutaneously a NOD/SCID/ Il2rg-knockout (NSG) mouse. The tumor tissues were harvested and transplanted in nude mice to establish mouse models bearing patient-derived xenograft (PDX) of cholangiocarcinoma expressing FGFR2-CCDC6 fusion protein. The PDX mouse models were divided into 4 groups for treatment with citrate buffer (control group), intragastric administration of 20 mg/kg ponatinib dissolved in citrate buffer (ponatinib group), weekly intraperitoneal injections of 50 mg/kg gemcitabine and 2.5 mg/ kg cisplatin (gemcitabine group), or ponatinib combined with gemcitabine and cisplatin at the same doses (10 mice in each group, and 9 mice were evaluated in ponatinib group). The expressions of p-FGFR, p-FRS2, p-AKT, p-ERK, CD31, and Ki-67 in the xenografts were evaluated with immunohistochemistry, and cell apoptosis was analyzed with cleaved caspase-3 (CC3) staining and TUNEL staining. Western blotting was used to detect the expressions of FGFR2, p-FGFR, AKT, p-AKT, ERK, p-ERK, FRS2 and p-FRS2 in the tumor tissues.@*RESULTS@#Compared with those in the control group, the mice in ponatinib group showed a significantly reduced tumor volume (@*CONCLUSIONS@#Ponatinib can regulate FGFR signaling to inhibit the proliferation and induce apoptosis of tumor cells in mice bearing patient-derived cholangiocarcinoma xenograft with FGFR2 fusion. FGFR inhibitor can serve as a treatment option for patients with cholangiocarcinoma with FGFR2 fusion.

Clinical and genetic findings of two cases with Apert syndrome / Hallazgos clínicos y genéticos de dos casos con síndrome de Apert

Abstract Background: Craniosynostosis is described as the premature fusion of cranial sutures that belongs to a group of alterations which produce an abnormal phenotype. Case report: Two unrelated female patients with clinical findings of Apert syndrome-characterized by acrocephaly, prominent frontal region, flat occiput, ocular proptosis, hypertelorism, down-slanted palpebral fissures, midfacial hypoplasia, high-arched or cleft palate, short neck, cardiac anomalies and symmetrical syndactyly of the hands and feet-are present. In both patients, a heterozygous missense mutation (c.755C>G, p.Ser252Trp) in the FGFR2 gene was identified. Conclusions: Two cases of Apert syndrome are described. It is important to recognize this uncommon entity through clinical findings, highlight interdisciplinary medical evaluation, and provide timely genetic counseling for the family.

Resumen Introducción: Las craneosinostosis se describen como la fusión prematura de las suturas craneales y resultan un grupo de alteraciones que producen un fenotipo anormal. Caso clínico: En este informe de casos se presentan dos pacientes de sexo femenino no emparentadas con hallazgos clínicos del síndrome de Apert, caracterizado por acrocefalia, región frontal prominente, occipucio plano, proptosis ocular, hipertelorismo, fisuras palpebrales hacia abajo, hipoplasia mediofacial, paladar alto o hendido, cuello corto, cardiopatía congénita y sindactilia simétrica en manos y pies. En ambas pacientes se identificó una mutación cambio de sentido en heterocigosis (c.755C>G, p.Ser252Trp) en el gen FGFR2. Conclusiones: Se presentan dos casos de síndrome de Apert. Es importante reconocer a través de los hallazgos clínicos esta entidad infrecuente, resaltar la evaluación médica interdisciplinaria y proporcionar un oportuno asesoramiento genético a la familia.

Advance in clinical research on Antley-Bixler syndrome / 中华医学遗传学杂志

Antley-Bixler syndrome (ABS) is a rare childhood disorder affecting skeletal development. Some patients may also have genital anomalies and impaired steroidogenesis. Diagnostic criteria for ABS has not been fully established, though craniosynostosis, midface hypoplasia and elbow synostosis are minimum requirements. The etiology of ABS is complex, which included autosomal dominant form caused by FGFR2 gene mutations, autosomal recessive form caused by POR gene mutations, and high oral dose of fluconazole during pregnancy. Patients may die from dyspnea due to upper respiratory tract obstruction. This review summarizes research progress on the clinical features, etiology, differential diagnosis, treatment and prevention of ABS.

Sindrome de apert / Opening syndrome

El síndrome de Apert, o acrocefalosindactilia tipo I, es un síndrome caracterizado por craneosinostosis, acompañada de sindactilia simétrica en las cuatro extremidades, alteraciones maxilofaciales, cutáneas y retardo mental variable. Este síndrome se debe a una mutación en el gen del receptor 2 del factor del crecimiento FIbroblástico (FGFR2), el cual se expresa de manera autosómica dominante (AD). Caso Clínico: Se presenta caso de recién nacido masculino, Capurro de 38 semanas aproximadamente, con las características fenotípicas clásicas de este síndrome:(como) la acrocefalia y la sindactilia en manos y pies.

Apert syndrome, or acrocephalosyndactyly type I, is a syndrome characterized by craniosynostosis, syndactyly accompanied symmetrical in all four extremities, maxillofacial abnormalities, mental retardation, skin and variable. This syndrome is caused by a mutation in the gene for the receptor 2 broblástico growth factor (FGFR2), which is expressed as an autosomal dominant (AD). Case Report: We report the case of a newborn male, approximately 38 weeks Capurro, with classical phenotypic features of this syndrome as acrocephaly and syndactyly of hands and feet.

The significance of keratinocyte in hyperproliferation of middle ear cholesteatoma / 临床耳鼻咽喉头颈外科杂志

OBJECTIVE@#In order to investigate the interaction between the cytokines and keratinocyte and determine the role of cytokines in hyperproliferative of chronic otitis media with cholesteatoma, we observe the expression of matrix metalloproteinase 9 (MMP9), vascular endothelial growth factor (VEGF), keratinocyte growth factor (KGF) and its receptor (KGFR) in middle ear cholesteatoma.@*METHOD@#We examined the expression of MMP9, VEGF, KGF, KGFR and Ki-67 by immunohistochemistry in 50 specimens from chronic otitis media with cholesteatoma and 15 specimens from the normal skin of external auditory meatus. Ki-67 as an evaluation of cholesteatoma proliferation markers were used to detect the keratinocyte proliferative activity.@*RESULT@#(1) The expression of VEGF and MMP9 in cholesteatoma specimens was higher than normal skin, and the difference was statistically significant (t = 4.914, P < 0.01; t = 3.284, P < 0.01). (2) The expression of KGF and KGFR in middle ear tissues was higher than normal skin, and the difference was statistically significant (t = 4.814, P < 0.01; t = 3.104, P < 0.01); The expression of KGF and KGFR increased, and the expression of Ki-67 also correspondly increased in the cholesteatoma. (3) In the tissue MMP9 and VEGF were positive. Mean optical density increased as well. KGF expression also increased accordingly.@*CONCLUSION@#MMP9, VEGF, KGF and KGFR proteins played an important role in hyperproliferation of cholesteatoma tissues. VEGF, MMP9 and KGF had a synergistic effect in hyperproliferation of cholesteatoma tissues.

Prognosis of Pregnancy-Associated Gastric Cancer: An Age-, Sex-, and Stage-Matched Case-Control Study

BACKGROUND/AIMS: Pregnancy-associated gastric cancer is a rare condition. This case-control study was performed to identify the clinicopathological features and prognostic factors of pregnancy-associated gastric cancer. METHODS: All consecutive patients who presented to our tertiary referral hospital with pregnancy-associated gastric cancer from 1991 to 2012 were identified. Two age-, sex-, and stage-matched controls for each case were also identified from the records. Clinicopathological, gynecological, and oncological outcomes were recorded. Immunohistochemical staining was performed for estrogen receptor, progesterone receptor, epidermal growth factor receptor, human epidermal growth factor receptor, and E-cadherin. Fluorescence in situ hybridization was performed for fibroblast growth factor receptor 2. RESULTS: The median overall survival rates of the pregnancy-associated gastric cancer and control groups were 7.0 months and 15.0 months, respectively (p=0.189). Poor prognostic factors included advanced stage and tumor location in the corpus or the entire stomach but not pregnancy status or loss of E-cadherin. Pregnancy-associated gastric cancer was associated with a longer time from diagnosis to treatment (21 days vs 7 days, p=0.021). The two groups did not differ in the expression of the receptors or E-cadherin. CONCLUSIONS: The dismal prognosis of pregnancy-associated gastric cancer may related to the tumor stage and location rather than to pregnancy itself.

Analysis of FGFR2 gene mutations in two Chinese families with Crouzon syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect potential mutations of fibroblast growth factor receptor 2 gene (FGFR2) in two Chinese families with Crouzon syndrome.</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood leukocytes of 20 members from two affected families. All of the 18 exons of the FGFR2 gene were amplified with polymerase chain reaction and sequenced after purification.</p><p><b>RESULTS</b>A missense mutation c.868T>C (p.W290R) in exon 8 of the FGFR2 gene was found solely in 2 affected members from family 1. Another missense mutation c.833G>T (p.C278F) in exon 8 was found solely in 5 affected members of family 2.</p><p><b>CONCLUSION</b>The missense mutations of the FGFR2 gene are responsible for the Crouzon syndrome in the two families. The c.868T>C missense mutation is reported for the first time in Chinese population.</p>

Case-Control Study on the Fibroblast Growth Factor Receptor 2 Gene Polymorphisms Associated with Breast Cancer in Chinese Han Women / 한국유방암학회지

PURPOSE: Genetic variation in fibroblast growth factor receptor 2 (FGFR2) is a newly described risk factor for breast cancer. This study aimed to evaluate the association of four single nucleotide polymorphisms (SNPs) in FGFR2 with breast cancer in Han Chinese women. METHODS: Two hundred three women with breast cancer and 200 breast cancer-free age-matched controls were selected. Four SNPs (rs2981579, rs1219648, rs2420946, and rs2981582) and their haplotypes were analyzed to test for their association with breast cancer susceptibility. The presence of the four FGFR2 SNPs was determined by polymerase chain reaction-restriction fragment length polymorphism analysis. RESULTS: A statistically significant difference was observed in the frequency of rs2981582 in the FGFR2 gene (p 3%) haplotypes were identified. Three of these haplotypes, CGTC (odds ratio [OR], 0.613; 95% confidence interval [CI], 0.457-0.82; p=0.001), TGTC (OR, 6.561; 95% CI, 2.064-20.854; p<0.001), and CATC (OR, 12.645; 95% CI, 1.742-91.799; p=0.001) were significantly associated with breast cancer risk. CONCLUSION: Our findings indicated that the SNP rs2981582 and haplotypes CGTC, TGTC, and CATC in FGFR2 may be associated with an increased risk of breast cancer in Han Chinese women.

Apert and Pfeiffer Syndromes: A Report of Two Cases / 대한소아신경학회지

Craniosysostosis syndrome is caused by premature fusion of bones of skull and face during fetal development. It is related to Fibroblast growth factor receptor gene and most common craniosynostosis syndromes are Apert, Pfeiffer and Crouzon. Apert syndrome is one of the severe type of craniosynostosis syndromes which shows mutations in the Fibroblast growth factor receptor 2 (FGFR2) gene. Pfeiffer syndrome is also related with FGFR 1 or 2 gene mutation. We experienced two patients with craniosynostosis syndromes, Apert syndrome and Pfeiffer syndrome. The first baby was a in-born female baby presented with syndactly of the hands and feet and facial dysmorphism including shallow orbit with deep crease above eye brow. Apert syndrome was confirmed by the presence of a mutation in FGFR2. The second patient visited our developmental delay clinic due to developmental delay at seven month old age. He showed facial dysmorphism including cloverleaf-shaped skull, micrognathia, low set ears, low nasal bridge and high-arched palate, but there were no syndactly or limb anomalies. He was suspected of Pfeiffer syndrome, however his FGFR2 gene study was normal. These patients need multidisciplinary team management and regular follow up for visual, auditory, and cognitive development functions Pediatricians have important role on recognizing the patients with facial dysmorphism, planning to evaluate accompanying anomalies and making appropriate decisions about the timing of surgical management to minimize growth and cognitive impairments.

p.Ser252Trp and p.Pro253Arg mutations in FGFR2 gene causing Apert syndrome: the first clinical and molecular report of Indonesian patients

Apert syndrome (AS) is a rare autosomal dominant disorder characterised by craniosynostosis and limb malformations, and is associated with congenital heart disease and other systemic malformations, including intellectual disability. We report two Indonesian patients with AS, in whom molecular analysis detected p.Ser252Trp (c.755C>G) and p.Pro253Arg (c.758C>G) mutations in the fibroblast growth factor receptor 2 (FGFR2) gene, respectively. Although the syndrome has been frequently described, this is the first clinical report of AS confirmed by molecular analysis in Indonesia. The difference in severity of clinical features in the two patients may be consistent with a genotype-phenotype correlation of the FGFR2mutation. The management of individuals with AS is best achieved within a multidisciplinary setting. However, in most developing countries, early intervention may be delayed due to late diagnosis, a lack of facilities and financial constraints. This report underpins the benefits of early diagnosis for AS management.

Effects of Busui Shengxue Granule on bFGF and bFGFR in bone marrow derived stroma cells of chronic aplastic anemia patients / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the therapeutic effects of Busui Shengxue Granule (BSSXG) on chronic aplastic anemia (CAA) patients and its effects on bone marrow derived stroma cells (BMDSCs) correlated cytokines.</p><p><b>METHODS</b>One hundred and twenty-four patients with CAA were randomly assigned to two groups according to the random digit table. Patients in the test group (61 cases) were treated with BSSXG, while those in the control group (63 cases) were treated with Zaizao Shengxue Tablet (ZST). The therapeutic course was 6 months for all. Besides, 10 healthy subjects were recruited as the normal control group. Changes of the symptom integral, therapeutic efficacy judgment, and changes of peripheral hemogram of patients were observed. The mRNA expression of b-fibroblast growth factors (bFGF) and b-fibroblast growth factors receptor (bFGFR) were detected by reverse transcription PCR.</p><p><b>RESULTS</b>The total effective rate of the test group was 75.0% (45/61), higher than that of the control group (58.7%, 37/63). Its symptom integral and peripheral hemogram were obviously improved, better than those of the control group (P < 0.05, P < 0.01). The mRNA expressions of bFGF and bFGFR of the test group were obviously lower than those of the normal control group (P < 0.05, P < 0.01). They were somewhat improved after treatment in the two groups, with better results obtained in the test group.</p><p><b>CONCLUSIONS</b>BSSXG showed better clinical effects. It could improve the symptom integral and peripheral hemogram of CAA patients, improve the clinical efficacy, and regulate the expression levels of bFGF and bFGFR. It improved the hematopoietic microenvironment and promoted the hematopoiesis of the bone marrow through regulating the proliferation and oriental differentiation of stroma cells, and promoting the bone marrow angiogenesis.</p>

Effects of moxibustion on the expressions of hippocampal VEGF, flt-1, bFGF, and bFGF-r in vascular dementia rats / 中国中西医结合杂志

<p><b>OBJECTIVE</b>To observe the expression levels of hippocampal vascular endothelial growth factor (VEGF), fms-like tyrosine kinase-1 (flt-1), basic fibroblast growth factor (bFGF), and basic fibroblast growth factor receptor (bFGF-r) in vascular dementia (VD) rats, thus studying the angiogenesis mechanism of moxibustion in VD.</p><p><b>METHODS</b>Sixty male elderly Wistar rats were selected. The VD rat model was prepared by bilateral carotid artery occlusion and reperfusion of sodium nitroprusside injection. The model rats were divided into 3 groups by the random digit table, i. e., the moxibustion group, the Western medicine group, and the model group. A sham-operation control group was also set up. In the moxibustion group rats was acupunctured at Baihui (GV20), Shenting (GV14), and Dazhui (GV24). Aniracetam was given to rats in the Western medicine group by gastrogavage for 2 therapeutic courses, 15 days as one course. The learning and memory results were observed by the neuroethological score in combination of step-down avoidance test before treatment and by the end of the 2nd course respectively. The expression levels of hippocampal VEGF, flt-1, bFGF, and bFGF-r of all rats were detected using immunohistochemical assay.</p><p><b>RESULTS</b>After 2 courses of treatment, statistical difference existed in the latent period, the error times, and the neuroethological score in the moxibustion group and the Western medicine group when compared with the model group (P < 0.01, P < 0.05). Statistical difference existed in the latent period and the neuroethological score between the moxibustion group and the Western medicine group (P < 0.05), which indicated that moxibustion and Western medicine showed significant effects in improving the latent period, decreasing the error times and the neuroethological score. Better results were obtained in the moxibustion group than in the Western medicine group (P < 0.01, P < 0.05). Statistical difference of the average grey level (AGL) of hippocampal VEGF, flt-1, and bFGF existed in the moxibustion group and the Western medicine group when compared with the model group. Statistical difference of the bFGF-r expression existed only between the moxibustion group and the model group. Statistical difference of the VEGF and flt-1 expressions existed between the moxibustion group and the Western medicine group (P < 0.05).</p><p><b>CONCLUSIONS</b>Moxibustion showed confirmative effects in improving the behavioral score and memory performance in VD rats. Its mechanisms might lie in that moxibustion regulated and controlled the expression levels of hippocampal VEGF, flt-1, bFGF, and bFGF-r in VD rats. Particularly it up-regulated the expression levels of key factors VEGF and flt-1, promoted the angiogenesis in the vital parts, and ultimately stimulated the repairing mechanisms of cerebral nerve injury.</p>

Effects of dexamethasone and vitamin B12 on expression of fibroblast growth factor 10 and fibroblast growth factor receptor 2b during early palatogenesis / 华西口腔医学杂志

<p><b>OBJECTIVE</b>To observe the alteration of fibroblast growth factor 10 (Fgf10) and fibroblast growth factor receptor 2 (Fgfr2b) signal in mouse embryonic palate after dexamethasone and vitamin B12 exposure.</p><p><b>METHODS</b>Dams were divided teratogenetic group, antagomistic group and control group and were respectively injected dexamethasone, dexamethasone and vitamin B12, and normal sodium. Dams were killed and fetus was collected at embryo 12.5 and 13.5 day. The expression of Fgf10 and Fgfr2b and mesenchymal cells proliferation of mouse embryonic by western blotting and BrdU assay were checked.</p><p><b>RESULTS</b>Fgf10 and Fgfr2b expression was down-regulated and mesenchymal cells proliferation was inhibited significantly after dexamethasone exposure. After vitamin B12 treatment, Fgf10 and Fgfr2b expression did not restore, but cells proliferation was recovered.</p><p><b>CONCLUSION</b>Dexamethasone and vitamin B12 affected the expression of Fgf10 and Fgfr2b of mouse embryonic palate and mesenchyme cells proliferation, but the change was disaccord.</p>

Experssion of human FGFR2IIIc and its S252W mutant in MDA-MB-231 breast cancer cells with adenovirus vectors / 生物工程学报

To study the functions of human Fibroblast growth factor receptor 2IIIc (FGFR2IIIc) gene in cancer cells, breast cancer cells MDA-MB-231 were infected by recombinant adenoviruses containing FGFR2IIIc and its S252W mutant, respectively. FGFR2IIIc gene was amplified from an existing plasmid and its S252W mutant was obtained by overlapping extension PCR. These two genes were separately cloned into the adenoviral shuttle plasmid pAdTrack-CMV, confivmed by DNA sequencing linearized, and co-transformed into Escherichia coli BJ-5183 with the adenoviral vector pAdEasy-1. The resulting recombinant expression vectors Ad-FGFR2IIIc and Ad-FGFR2IIIcS252W were linearized and transfected into HEK293A cells to get adenoviral particles. GFP was used to verify the gene expression. The recombinant adenoviral particles were harvested, titrated, and then infected MDA-MB-231 cells. The expression of FGFR2IIIc and its S252W mutant were examined by RT-PCR and Western blotting, and the effect of these recombinant adenoviruses on MDA-MB-231 cell proliferation was analyzed by 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) and flow cytometry. The results showed the recombinant adenoviral particles could infect MDA-MB-231 cells and express the target proteins. MTT showed that both FGFR2IIIc and its S252W mutant inhibited MDA-MB-231 cell proliferation, but the mutant was more effective. Flow cytometry showed that both FGFR2IIIc and its S252W mutant arrested MDA-MB-231 cell cycle at G0/G1 phase, resulting in low cell proliferation.

Keratinocyte growth factor phage model peptides can promote epidermal cell proliferation without tumorigenic effect / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Keratinocyte growth factor (KGF) significantly influences epithelial wound healing. The aim of this study was to isolate KGF phage model peptides from a phage display 7-mer peptide library to evaluate their effect on promoting epidermal cell proliferation.</p><p><b>METHODS</b>A phage display 7-mer peptide library was screened using monoclonal anti-human KGF antibody as the target. Enzyme linked immunosorbent assay (ELISA) was performed to select monoclonal phages with good binding activity. DNA sequencing was done to find the similarities of model peptides. Three-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay, immunofluorescence assay and quantitative real-time PCR analysis were employed to evaluate the effect of the phage model peptides on epidermal cells.</p><p><b>RESULTS</b>Thirty-three out of fifty-eight (56.9%) of the isolated monoclonal phages exhibited high binding activity by ELISA. Ten of fifteen obtained phage model peptides were similar to KGF or epidermal growth factor (EGF). MTT assay data showed that four (No. 1 - 4) of the ten phage model peptides could promote epidermal cell proliferation. The expression of keratinocyte growth factor receptor (KGFR) mRNA in the KGF control group and the two phage model peptide groups (No. 1 and No. 2) increased. Expression of c-Fos mRNA and c-Jun mRNA in the KGF control group increased, but did not increase in the four phage model peptide groups (No.1 - 4).</p><p><b>CONCLUSION</b>Four phage model peptides isolated from the phage display 7-mer peptide library can safely promote epidermal cell proliferation without tumorigenic effect.</p>

A case of Pfeiffer syndrome with c833_834GC>TG (Cys278Leu) mutation in the FGFR2 gene / 소아과

Pfeiffer syndrome is a rare autosomal dominant disorder characterized by coronal craniosynostosis, brachycephaly, mid-facial hypoplasia, and broad and deviated thumbs and great toes. Pfeiffer syndrome occurs in approximately 1:100,000 live births. Clinical manifestations and molecular genetic testing are important to confirm the diagnosis. Mutations of the fibroblast growth factor receptor 1 (FGFR1) gene or FGFR2 gene can cause Pfeiffer syndrome. Here, we describe a case of Pfeiffer syndrome with a novel c833_834GC>TG mutation (encoding Cys278Leu) in the FGFR2 gene associated with a coccygeal anomaly, which is rare in Pfeiffer syndrome.

Association of FGFR2 gene polymorphism with estrogen receptor positive breast cancer detected by fluorescent quantitative PCR / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the association of fibroblast growth factor receptor 2 gene (FGFR2) rs2981582 polymorphism with breast cancer in Chinese women.</p><p><b>METHODS</b>A case-control study was performed in 936 breast cancer patients and 471 patients with benign breast diseases by using a novel fluorescent quantitative PCR method.</p><p><b>RESULTS</b>The numbers and frequencies of genotypes CC, CT, and TT in the control group were 234(49.68%), 181(38.43%) and 56(11.89%) respectively. The numbers and frequencies of genotypes CC, CT, and TT in the breast cancer group were 426(44.56%), 400(41.84%) and 130(13.60%) respectively. And no significant difference was found between the two groups (P=0.183). However, stratified analysis found that the numbers and frequencies of genotypes CC, CT, TT in the estrogen receptor(ER) positive subgroup of breast cancer patients were 189(41.27%), 202(46.12%) and 67(14.63%) respectively, and significant difference was observed compared with control group (P=0.035).</p><p><b>CONCLUSION</b>Association was found in the single nucleotide polymorphism(SNP) of the rs2981582 locus of intron 2 in FGFR2 gene between the ER positive breast cancer patients and control patients with benign breast diseases. The fluorescent quantitative PCR is a specific, easy-to-operate, low-expense method and is suitable for SNP detection in large scale samples.</p>

FGFR2 gene mutation in a Chinese patient with Apert syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To determine the disease-causing mutation in a Chinese patient with Apert syndrome (AS).</p><p><b>METHODS</b>Genomic DNA was extracted from peripheral blood samples of the AS patient and his parents. Polymerase chain reaction (PCR) was used to amplify the exons 7 and 9 of fibroblast growth factor receptor 2 (FGFR2) gene. Then PCR products were sequenced bi-directionally.</p><p><b>RESULTS</b>A heterozygous 934C to G transversion in exon 7 of the FGFR2 gene was detected in the patient, which resulted in the substitution of tryptophan residue for serine at position 252 of FGFR2 protein (S252W). This mutation has been reported in AS patients previously.</p><p><b>CONCLUSION</b>This Chinese AS results from the 934 C to G mutation in exon 7 of FGFR2 gene.</p>

Isotretinoin Treatment for the Recalcitrant Acne on a Patient with Apert Syndrome / 대한피부과학회지

Apert syndrome is a rare genetic craniofacial disorder associated with premature fusion of multiple cranial sutures and syndactyly. It is caused by mutation in the fibroblast growth factor receptor 2 genes. The clinical findings are characterized by the typical dysmorphic facial features, including hypertelorism, proptosis and cleft palate. Most of these patients have widespread, severe acne involving the face, chest, back and forearms during puberty and the acne is unresponsive to conventional treatments. We report here on a patient with the recalcitrant acne of Apert syndrome and the patient had failed to respond to conventional acne treatment, but the acne was successfully treated with isotretinoin

FGFR2 gene mutation in a family with Crouzon syndrome and a sporadic Crouzon syndrome patient / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To detect the gene mutation of fibroblast growth factor receptor (FGFR2)in a Crouzon syndrome family and a sporadic patient.</p><p><b>METHODS</b>The genomic DNA from 10 members in the Crouzon syndrome family, as well as a sporadic patient, was extracted. Then exons 8 and 10 of FGFR2 gene and their flanking sequences were amplified by polymerase chain reaction. Some of the family members were studied by only amplifying exon 8. Finally, the PCR products were purified and sequenced.</p><p><b>RESULTS</b>The G to T transversion mutation (heterozygote) at nucleotide 833 in exon 8 of FGFR2 (C278F), was found both in the patients of the family and the sporadic patient.</p><p><b>CONCLUSION</b>FGFR2 gene mutation is responsible for the pathogenesis of Crouzon syndrome in these patients.</p>