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1.
Einstein (Säo Paulo) ; 20: eAO6450, 2022. tab, graf
Article in English | LILACS | ID: biblio-1364794

ABSTRACT

ABSTRACT Objective To understand the feasibility of FGFR3 tests in the Brazilian public health context, and to sample the mutational burden of this receptor in high-grade muscle invasive bladder cancer. Methods A total of 31 patients with high-grade muscle-invasive bladder cancer were included in the present study. Either transurethral resection of bladder tumor or radical cystectomy specimens were analyzed. Formalin-fixed paraffin-embedded tissue blocks were sectioned, hematoxylin and eosin stained, and histologic sections were reviewed. Total RNA was extracted using the RNeasy DSP formalin-fixed paraffin-embedded kit. Qualitative results were displayed in Rotor-Gene AssayManager software. Results Six patients were excluded. From the samples analyzed, four (16.7%) were considered inadequate and could not have their RNA extracted. Two patients presented FGFR3 mutations, accounting for 9.5% of material available for adequate analysis. The two mutations detected included a Y373C mutation in a male patient and a S249C mutation in a female patient. Conclusion FGFR3 mutations could be analyzed in 84% of our cohort and occurred in 9.5% of patients with high-grade muscle invasive bladder cancer in this Brazilian population. FGFR3 gene mutations are targets for therapeutic drugs in muscle-invasive bladder cancer. For this reason, know the frequency of these mutations can have a significant impact on public health policies and costs provisioning.


Subject(s)
Urinary Bladder Neoplasms/genetics , Carcinoma, Transitional Cell/genetics , Carcinoma, Transitional Cell/metabolism , Carcinoma, Transitional Cell/pathology , Receptor, Fibroblast Growth Factor, Type 3/genetics , Receptor, Fibroblast Growth Factor, Type 3/metabolism , Brazil , RNA , Prevalence , Eosine Yellowish-(YS) , Hematoxylin , Muscles/metabolism , Muscles/pathology , Mutation
2.
Article in Chinese | WPRIM | ID: wpr-928622

ABSTRACT

OBJECTIVES@#To study the clinical features and fibroblast growth factor receptor 3 (FGFR3) gene mutations of children with achondroplasia (ACH) through an analysis of 17 cases.@*METHODS@#A retrospective analysis was performed on the clinical data and FGFR3 gene detection results of 17 children with ACH who were diagnosed from January 2009 to October 2021.@*RESULTS@#Of the 17 children with ACH, common clinical manifestations included disproportionate short stature (100%, 17/17), macrocephaly (100%, 17/17), trident hand (82%, 14/17), and genu varum (88%, 15/17). The common imaging findings were rhizomelic shortening of the long bones (100%, 17/17) and narrowing of the lumbar intervertebral space (88%, 15/17). Major complications included skeletal dysplasia (100%, 17/17), middle ear dysfunction (82%, 14/17), motor/language developmental delay (88%, 15/17), chronic pain (59%, 10/17), sleep apnea (53%, 9/17), obesity (41%, 7/17), foramen magnum stenosis (35%, 6/17), and hydrocephalus (24%, 4/17). All 17 children (100%) had FGFR3 mutations, among whom 13 had c.1138G>A hotspot mutations of the FGFR3 gene, 2 had c.1138G>C mutations of the FGFR3 gene, and 2 had unreported mutations, with c.1252C>T mutations of the FGFR3 gene in one child and c.445+2_445+5delTAGG mutations of the FGFR3 gene in the other child.@*CONCLUSIONS@#This study identifies the unreported mutation sites of the FGFR3 gene, which extends the gene mutation spectrum of ACH. ACH is a progressive disease requiring lifelong management through multidisciplinary collaboration.


Subject(s)
Achondroplasia/genetics , Child , Humans , Mutation , Osteochondrodysplasias/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics , Retrospective Studies
3.
Article in Chinese | WPRIM | ID: wpr-879470

ABSTRACT

OBJECTIVE@#To explore strategies of prenatal genetic testing for fetuses featuring abnormal skeletal development.@*METHODS@#Clinical data of 17 fetuses with skeletal dysplasia was collected. The results of genetic testing and outcome of pregnancy were analyzed.@*RESULTS@#For 12 fetuses, the femur-to-foot length ratio was less than 0.9. Thirteen fetuses had a positive finding by genetic testing. One fetus was diagnosed with chromosomal aneuploidy, three were diagnosed with microdeletion/microduplications, and nine were diagnosed with hereditary bone diseases due to pathological variants of FGFR3, COL1A2, GPX4 or ALPL genes.@*CONCLUSION@#For fetuses with skeletal dysplasia characterized by short femur, in addition to chromosomal karyotyping and microarray analysis, sequencing of FGFR3 and other bone disease-related genes can improve the diagnostic rate.


Subject(s)
Bone Diseases, Developmental/genetics , Female , Fetus/diagnostic imaging , Genetic Testing , Humans , Karyotyping , Pregnancy , Prenatal Diagnosis , Receptor, Fibroblast Growth Factor, Type 3/genetics , Ultrasonography, Prenatal
4.
Clinics ; 73: e324, 2018. graf
Article in English | LILACS | ID: biblio-952808

ABSTRACT

OBJECTIVES: To characterize the natural history of 39 achondroplastic patients diagnosed by clinical, radiological and molecular assessments. METHODS: Observational and retrospective study of 39 patients who were attended at a public tertiary level hospital between 1995 and 2016. RESULTS: Diagnosis was made prenatally in 11 patients, at birth in 9 patients and within the first year of life in 13 patients. The most prevalent clinical findings were short stature, high forehead, trident hands, genu varum and macrocephaly. The most prevalent radiographic findings were rhizomelic shortening of the long bones and narrowing of the interpediculate distance of the caudal spine. There was motor developmental delay in 18 patients and speech delay in 16 patients. The most common clinical intercurrences were middle ear dysfunction, sleep apnea, limb pain and obesity from 2 to 9 years of age. One patient was large for the gestational age but did not develop obesity. One patient developed hydrocephalus at 10 years old. The current age of the patients varies from 15 months to 36 years. The molecular study performed by Sanger sequencing of the common heterozygous mutation 1138G>A in FGFR3 was positive in all patients. Four cases were inherited, and 35 were sporadic (paternal age from 19 to 66 years). CONCLUSIONS: The diagnoses were made early based on clinical and radiographic findings. All cases were confirmed molecularly. Despite presenting a benign course, it is necessary to establish a systematic protocol for the surveillance of these patients due to the common clinical intercurrences.


Subject(s)
Humans , Male , Female , Infant, Newborn , Adult , Middle Aged , Aged , Young Adult , Achondroplasia/diagnosis , Achondroplasia/pathology , Achondroplasia/genetics , Radiography , Retrospective Studies , Follow-Up Studies , Age Factors , Molecular Diagnostic Techniques , Receptor, Fibroblast Growth Factor, Type 3/genetics , Mutation
5.
Oman Medical Journal. 2011; 26 (3): 196-197
in English | IMEMR | ID: emr-125053

ABSTRACT

Thanatophoric dysplasia is the lethal skeletal dysplasia characterized by marked underdevelopment of the skeleton and short-limb dwarfism. The child will be having a short neck, narrow thoracic cage and protuberant abdomen. Other anatomical features include a relatively enlarged head with frontal bossing, prominent eyes, hypertelorism and the depressed nasal bridge. The diagnosis is usually made with the ultrasonography in the second trimester. In this study we report a case of this rare entity with emphasis on its anatomical features, abnormalities and clinical profile with relevant review of literature


Subject(s)
Humans , Male , Receptor, Fibroblast Growth Factor, Type 3/genetics , Mutation , Pregnancy Outcome , Congenital Abnormalities , Thanatophoric Dysplasia/diagnostic imaging , Ultrasonography, Prenatal
6.
Article in English | WPRIM | ID: wpr-155854

ABSTRACT

The Muenke syndrome (MS) is characterized by unicoronal or bicoronal craniosynostosis, midfacial hypoplasia, ocular hypertelorism, and a variety of minor abnormalities associated with a mutation in the fibroblast growth factor receptor 3 (FGFR3) gene. The birth prevalence is approximately one in 10,000 live births, accounting for 8-10% of patients with coronal synostosis. Although MS is a relatively common diagnosis in patients with craniosynostosis syndromes, with autosomal dominant inheritance, there has been no report of MS, in an affected Korean family with typical cephalo-facial morphology that has been confirmed by molecular studies. Here, we report a familial case of MS in a female patient with a Pro250Arg mutation in exon 7 (IgII-IGIII linker domain) of the FGFR3 gene. This patient had mild midfacial hypoplasia, hypertelorism, downslanting palpebral fissures, a beak shaped nose, plagio-brachycephaly, and mild neurodevelopmental delay. The same mutation was confirmed in the patient's mother, two of the mother's sisters and the maternal grandfather. The severity of the cephalo-facial anomalies was variable among these family members.


Subject(s)
Adult , Asians/genetics , Child, Preschool , Craniosynostoses/genetics , DNA Mutational Analysis , Female , Humans , Hypertelorism/genetics , Korea , Male , Mutation , Pedigree , Phenotype , Receptor, Fibroblast Growth Factor, Type 3/genetics , Skull/abnormalities , Syndrome , Treatment Outcome
7.
Article in Korean | WPRIM | ID: wpr-77845

ABSTRACT

Involvement of the central nervous system is very uncommon in multiple myeloma, observed in approximately 1% of the multiple myeloma patients. We report a case of central nervous system myelomatosis with complex chromosome aberrations in a 62-yr-old female patient, who had previously been diagnosed as multiple myeloma. Fluorescent in situ hybridization revealed 13q deletion, p53 gene deletion and IGH/FGFR3 rearrangement and chromosomal study showed complex chromosome aberrations. After four cycles of chemotherapy, the patient was admitted to the hematology department with severe headache. Plasma cells were found in the cerebrospinal fluid (CSF), and CSF immunoelectrophoresis revealed abnormal precipitin arcs against anti-IgG and anti-lambda antisera. She was given systemic chemotherapy and eight courses of intrathecal chemotherapy, which cleared plasma cells in the CSF. Two months later, she was given autologous stem cell transplantation. Three months after stem cell transplantation, central nervous system myelomatosis progressed to plasma cell leukemia and two months later,the patient expired.


Subject(s)
Antineoplastic Agents/therapeutic use , Central Nervous System Neoplasms/diagnosis , Cerebrospinal Fluid/cytology , Chromosome Deletion , Combined Modality Therapy , Disease Progression , Female , Gene Deletion , Humans , Immunoelectrophoresis , In Situ Hybridization, Fluorescence , Leukemia, Plasma Cell/diagnosis , Middle Aged , Multiple Myeloma/diagnosis , Plasma Cells/pathology , Precipitins/metabolism , Receptor, Fibroblast Growth Factor, Type 3/genetics , Stem Cell Transplantation , Translocation, Genetic , Transplantation, Autologous , Tumor Suppressor Protein p53/genetics
8.
Indian J Pediatr ; 2009 Feb; 76(2): 147-9
Article in English | IMSEAR | ID: sea-79213

ABSTRACT

OBJECTIVE: Mutation analysis in Indian children with achondroplasia. METHODS: We studied 11 sporadic cases of achondroplasia. Mutation analysis was done by PCR/RFLP (Polymerase chain reaction/Restriction fragment length polymorphism) method. RESULTS: Nine of the 11 cases had mutation G-->A at 1138 nucleotide position in transmembrane domain of fibroblast growth-factor receptor 3 (FGFR3) gene. Substitution G-->A is a common recurrent mutation reported worldwide. In two cases we could not detect any common mutation and also in entire region of transmembrane domain sequenced. There is possibility of mutation in the other regions of FGFR3 gene in these two cases. CONCLUSION: Further study of these two cases is needed in order to define other genotypes resulting in achondroplasia. Postnatal diagnosis of achondroplasia depends on clinical and radiological features. Mutation detection is mainly useful for prenatal diagnosis.


Subject(s)
Achondroplasia/diagnosis , Achondroplasia/epidemiology , Achondroplasia/genetics , Child , DNA Mutational Analysis , Humans , India/epidemiology , Molecular Biology/methods , Point Mutation/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics
9.
Article in English | IMSEAR | ID: sea-40676

ABSTRACT

Thanatophoric dysplasia is the most common neonatal lethal skeletal dysplasia with an estimated incidence of 1 in 20,000 live births. This condition shares some similarity of radiological findings with other types of lethal skeletal dysplasias. Definite diagnosis is necessary for accurate medical and genetic counseling. The authors describe a male neonate who had characteristic features of thanatophoric dysplasia type I including severe shortening of limbs with redundant skin folds, large head, frontal bossing, depressed nasal bridge, and narrow thoracic cage with severe respiratory insufficiency. Postmortem radiographs revealed short ribs, flat vertebral bodies (platyspondyly), hypoplastic iliac bones, marked shortening of long bones including short and mild bowing of both femora, oval radiolucent area of proximal femur. Molecular analysis of Fibroblast Growth Factor Receptor 3 (FGFR3) gene identified a de novo mutation, p.R248C, in exon 7.


Subject(s)
Female , Humans , Infant, Newborn , Male , Mutation , Pregnancy , Pregnancy Outcome , Receptor, Fibroblast Growth Factor, Type 3/genetics , Thailand , Thanatophoric Dysplasia/genetics
10.
J Indian Med Assoc ; 2005 Oct; 103(10): 536, 538
Article in English | IMSEAR | ID: sea-96455

ABSTRACT

Achondroplasia is a rare disorder occurring 1 in 1 5,000 to 1 in 40,000 live births. It is, however, the commonest cause of short-limbed dwarfism. It is a genetic disorder and inherited as an autosomal dominant trait but most cases (80%) are due to mutations of fibroblast growth factor receptor 3 (FGFR3). These individuals have normal mental and sexual development, and life span may be normal. Certain gynaecological problems like infertility, menorrhagia, dysmenorrhoea, leiomyomata and early menopause are more common in these patients. Information regarding obstetric behaviour in achondroplastic females is scarce in literature. However, problems such as pre-eclampsia, polyhydramnios, respiratory compromise, contracted pelvis necessitating lower section caesarean section, prematurity and foetal wastage, etc, have been reported. General anaesthesia is preferred to regional anaesthesia because of the spinal abnormalities. There is increased neonatal mortality due to hydrocephalus and thoracic cage abnormality. Such a patient is considered high risk in terms of anaesthesia and obstetric outcome and there is enough room for prenatal counselling and diagnosis. Here a case of achondroplasia with pregnancy is reported. The patient, an achondroplastic dwarf presented with 30 weeks pregnancy. She was prenatally screened with ultrasonography to rule out affection in baby. She had a caesarean section for contracted pelvis.


Subject(s)
Achondroplasia/diagnosis , Adult , Dwarfism , Female , Humans , Mutation , Pregnancy , Pregnancy Complications/genetics , Receptor, Fibroblast Growth Factor, Type 3/genetics
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