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Human Genomics Feb 2023Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described...
BACKGROUND
Mutations in NF1 gene could cause allelic disorders with clinical spectrum of Neurofibromatosis type 1 to Noonan syndrome. Here, a 7-year-old Iranian girl is described with Neurofibromatosis-Noonan syndrome due to a pathogenic variant in NF1 gene.
METHODS
Clinical evaluations were performed along with genetic testing using whole exome sequencing (WES). The variant analysis including pathogenicity prediction was also done using bioinformatics tools.
RESULTS
The chief compliant of the patient was short stature and lack of proper weight gain. Other symptoms were developmental delay, learning disability, inadequate speech skill, broad forehead, hypertelorism, and epicanthal folds, low set ears and webbed neck. A small deletion, c.4375-4377delGAA, was found in NF1 gene using WES. This variant was classified as pathogenic according to ACMG.
CONCLUSIONS
NF1 variants may show variable phenotypes among the patients; identifying such variants is helpful in therapeutic management of the disease. WES is considered as an appropriate test to diagnose Neurofibromatosis-Noonan syndrome.
Topics: Humans; Genes, Neurofibromatosis 1; Iran; Mutation; Neurofibromatoses; Neurofibromatosis 1; Noonan Syndrome; Female; Child
PubMed: 36803953
DOI: 10.1186/s40246-023-00460-0 -
Journal of Clinical Research in... Feb 2019We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS...
We report a detailed phenotypic, cytogenetic and molecular characterization of a patient prenatally diagnosed with Turner syndrome (TS). In addition to having typical TS clinical characteristics including webbed neck, high arched palate and coarctation of the aorta, the patient had features less frequently seen in TS. These included recurrent parathyroid adenomas, growth along the 75-90 centiles on the TS height curve despite minimal treatment with growth hormone, behavioral problems and evidence of gonadal dysgenesis with testicular-like structures, such as seminiferous tubules lined by Sertoli cells and a contiguous nodule of Leydig cells. While fluorescence hybridization (FISH) failed to detect Y-chromosome material in gonadal tissue or blood samples, chromosomal microarray analysis (CMA) confirmed X monosomy and a 4.69 Mb copy number loss on 1q31.2q31.3 (bp 192,715,814 to 197,401,180). This region contains the gene which has been associated with hyperparathyroidism-jaw tumor syndrome, features of which include recurrent, functional parathyroid adenomas and behavioral issues. This case illustrates how atypical features in a TS patient, such as robust growth and recurrent parathyroid adenomas, may suggest an underlying molecular etiology that should be explored by additional genetic diagnostic modalities. It is therefore appropriate in such cases to conduct further genetic testing, such as CMA and FISH, to explore other diagnostic possibilities and possibly prevent further complications.
Topics: Adult; Chromosomes, Human, Pair 1; Chromosomes, Human, X; Chromosomes, Human, Y; Female; Humans; Hyperparathyroidism; Monosomy; Sequence Deletion; Turner Syndrome; Young Adult
PubMed: 29739732
DOI: 10.4274/jcrpe.galenos.2018.2018.0005 -
Saudi Journal of Anaesthesia Jul 2011Noonan syndrome is a genetically transmitted autosomal dominant disorder characterized by various anatomic anomalies and pathophysiologic derangements. Anesthetic...
Noonan syndrome is a genetically transmitted autosomal dominant disorder characterized by various anatomic anomalies and pathophysiologic derangements. Anesthetic management in such cases poses a multitude of challenges, especially related to the airway management and maintenance of cardiovascular stability. We report a case of a 9-year-old male child weighing 24 kg, who was diagnosed as a case of Noonan syndrome and had undergone ligation of patent ductus arteriosus during early childhood. The child was operated on for release of bilateral neck bands under general anesthesia. The case report pertains to the successful airway and anesthetic management in the background of difficult airway and existence of various cardiac lesions.
PubMed: 21957424
DOI: 10.4103/1658-354X.84121 -
BMC Ophthalmology Nov 2013Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched...
BACKGROUND
Noonan syndrome is an autosomal, dominantly inherited disease; it is physically characterized by short stature, short neck, webbed neck, abnormal auricles, high arched palate, and cardiovascular malformation. Its pathological condition is thought to be due to a gain-of-function mutation in the Ras-mitogen-activated protein kinase (MAPK) signal transduction pathway. Eyelid abnormalities such as ocular hypertelorism and blepharoptosis are the most commonly observed eye complications.
CASE PRESENTATION
We report a case of Noonan syndrome associated with mature cataract that required operation. A 42-year-old man was diagnosed with Noonan syndrome at the age of 1 year. He underwent an eye examination after complaining of decreased visual acuity in the right eye and was diagnosed with mature cataract, which was treated by cataract surgery. There were no intraoperative complications, and the postoperative course was uneventful. Protein analysis of lens capsule and epithelium at capsulorhexis showed MAPK cascade proteins such as ERK and p38MAPK were upregulated. An abnormality in the PTPN11 gene was also observed; a potential mechanism of cataract onset may be that opacity of the lens rapidly progressed due to abnormal activation of the Ras-MAPK signal transduction pathway.
CONCLUSION
This case highlights the possible association of cataract formation with MAPK cascade protein upregulation in Noonan syndrome.
Topics: Adult; Cataract; Humans; Lens, Crystalline; MAP Kinase Signaling System; Male; Mitogen-Activated Protein Kinase 1; Noonan Syndrome
PubMed: 24219368
DOI: 10.1186/1471-2415-13-70 -
Hormone Research in Paediatrics 2014Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and...
BACKGROUND
Cockayne syndrome is an autosomal recessive, heterogeneous syndrome with classical features, including short stature, microcephaly, developmental delay, neuropathy, and photosensitivity. New genomic approaches offer improved molecular diagnostic potential.
METHODS
Whole-exome sequencing was employed to study a consanguineous extended family with severe short stature and variable presentations of peripheral neuropathy, lipoatrophy, photosensitivity, webbed neck, and hirsutism.
RESULTS
We identified a novel homozygous ERCC6 variant at the donor splice site of intron 9 (c.1992 + 3A>G), which was predicted to only slightly perturb splicing efficiencies. Assessment of primary fibroblast-derived mRNAs, however, revealed a dominant splicing species that utilized an unsuspected putative donor splice site within exon 9, resulting in predicted early protein termination (p.Arg637Serfs*34).
CONCLUSIONS
We describe a new splicing ERCC6 defect causal of Cockayne syndrome. The application of exome sequence analysis was integral to diagnosis, given the complexity of phenotypic presentation in the affected family members. The novel splicing defect, furthermore, illustrates how a seemingly minor change in the relative strength of a splice site can have significant biological consequences.
Topics: Cockayne Syndrome; Codon, Terminator; DNA Helicases; DNA Repair Enzymes; Exome; Female; High-Throughput Nucleotide Sequencing; Humans; Male; Point Mutation; Poly-ADP-Ribose Binding Proteins; RNA Splice Sites; RNA Splicing
PubMed: 25376329
DOI: 10.1159/000368192 -
Journal of Medical Case Reports Apr 2014Reports on cases of epilepsy in Turner syndrome are rare and most of them have cortical developmental malformations. We report the case of a Taiwanese patient with...
INTRODUCTION
Reports on cases of epilepsy in Turner syndrome are rare and most of them have cortical developmental malformations. We report the case of a Taiwanese patient with mosaic Turner syndrome with generalized tonic-clonic epilepsy and asymmetrical lateral ventricles but no apparent cortical anomaly.
CASE PRESENTATION
A 49-year-old Taiwanese woman without family history presented with infrequent generalized tonic-clonic epilepsy since she was 11 years old. On examination, her short stature, webbed neck, swelling of hands and feet, retrognathic face, and mild intellectual disability were noted. She had spontaneous menarche and regular menses. Brain magnetic resonance imaging showed asymmetrical lateral ventricles and diffuse subcortical white matter T2-weighted hyperintensities. Chromosome studies disclosed low aneuploid (10%) 45,X/46,XX/47,XXX mosaic Turner syndrome.
CONCLUSIONS
There is increasing evidence that epilepsy can be an uncommon presentation of Turner syndrome. Mosaic Turner syndrome with 47, XXX probably increases the risk of epilepsy but more research is needed to reach a conclusion. This case also strengthens our knowledge that Turner syndrome can be one of the pathologic bases of asymmetrical lateral ventricles. When a patient has idiopathic/cryptogenic epilepsy or asymmetrical lateral ventricles on brain images, the presence of a mild Turner phenotype warrants further chromosome studies.
Topics: Epilepsy, Generalized; Epilepsy, Tonic-Clonic; Female; Genotype; Humans; Lateral Ventricles; Magnetic Resonance Imaging; Middle Aged; Mosaicism; Turner Syndrome; White Matter
PubMed: 24694237
DOI: 10.1186/1752-1947-8-109 -
BMJ Case Reports May 2010We present the case of a 49-year-old Caucasian man whose main complaints were wart-like skin changes and scrotal lymphoedema. Furthermore, our patient showed signs of a...
We present the case of a 49-year-old Caucasian man whose main complaints were wart-like skin changes and scrotal lymphoedema. Furthermore, our patient showed signs of a common hereditary disease: lymphoedema, short stature, webbed neck, low frontal and posterior hairline, downslanting palpebral fissures, pale blue iris, broad nose, flat philtrum, and prominent nasolabial folds. His ears were low set and retroverted with a thick helix. However, no diagnosis was made for 49 years. The interdisciplinary dialogue of various specialists to make the final diagnosis is presented and discussed.
Topics: Chyle; Diagnosis, Differential; Humans; Lymphangiectasis; Male; Middle Aged; Noonan Syndrome; Warts
PubMed: 22750922
DOI: 10.1136/bcr.08.2009.2214 -
Frontiers in Medicine 2021Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma/Mitogen-activated protein kinase (RAS/MAPK) pathway and...
Noonan syndrome (NS) is an autosomal dominant multisystem disorder caused by the dysregulation of the Rat Sarcoma/Mitogen-activated protein kinase (RAS/MAPK) pathway and characterized by short stature, heart defects, pectus excavatum, webbed neck, learning disabilities, cryptorchidism, and facial dysmorphia. Villonodular synovitis is a joint disorder most common in young adults characterized by an abnormal proliferation of the synovial membrane. Multifocal Villonodular synovitis is a rare disease whose recurrent nature can make its management particularly difficult. Currently, there is no systemic therapy recommended in diffuse and recurrent forms, especially because of the fear of long-term side effects in patients, who are usually young. Yet, tyrosine kinase inhibitors seem promising to reduce the effects of an aberrant colony stimulating factor-1 (CSF-1) production at the origin of the synovial nodule proliferation. We present here the case of a 21-year-old woman with NS associated to diffuse multifocal villonodular synovitis (DMVS). Our clinical case provides therapeutic experience in this very rare association. Indeed, in association with surgery, the patient improved considerably: she had complete daily life autonomy, knee joint amplitudes of 100° in flexion and 0° in extension and was able to walk for 10 min without any technical assistance. To our knowledge, this is the first case of a patient suffering from DMVS associated with a Noonan syndrome treated with Glivec (oral administration at a dosage of 340 mg/m in children, until disease regression) on a long-term basis.
PubMed: 35111788
DOI: 10.3389/fmed.2021.817873 -
The Tohoku Journal of Experimental... Mar 2007A 45,X karyotype is one of the common chromosomal abnormalities characterized by short stature, lack of development of secondary sexual characteristics, webbed neck and...
A 45,X karyotype is one of the common chromosomal abnormalities characterized by short stature, lack of development of secondary sexual characteristics, webbed neck and cubitus valgus. This phenotype was described by Turner in 1938 and was called Turner syndrome (TS). About 40-60% of the patients with TS phenotype have a 45,X karyotype, the rest either have a structurally abnormal X or Y chromosome or mosaicism with a second cell line. Determination of Y chromosome derivatives in patients with a 45,X karyotype is important for the management of these patients due to increased risk of gonadoblastoma. Low level mosaicism of Y chromosome may be missed by cytogenetic methods. The aim of our study is to analyze cryptic Y chromosome derivatives using Y specific sequences in 40 Turkish patients with a pure 45,X karyotype. Fourteen different Y specific sequences along the Y chromosome were selected for the detection of cryptic Y chromosome material by PCR analysis. The present study demonstrated that 2 patients with a 45,X karyotype (5%) have Y specific sequences except sex related region Y (SRY). One of them had displayed enhanced virilisation whereas other showed no virilisation. In conclusion, it has been found by PCR analysis that 5% of patients with a 45,X karyotype have Y chromosome sequences in the absence of any marker chromosome by cytogenetic analysis. The data also suggest that the patients with a 45,X karyotype should be analyzed for the presence of Y chromosome derivatives by sensitive methods, such as PCR, in order to calculate the future risk of developing gonadoblastoma.
Topics: Adolescent; Adult; Child; Child, Preschool; Chromosomes, Human, Y; DNA Primers; Female; Humans; Infant; Male; Mosaicism; Polymerase Chain Reaction; Sex Chromosome Aberrations; Turkey; Turner Syndrome
PubMed: 17347549
DOI: 10.1620/tjem.211.243 -
American Journal of Medical Genetics.... Nov 2015Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint...
Linkeropathies are a group of syndromes characterized by short stature, radio-ulnar synostosis, decreased bone density, congenital contractures and dislocations, joint laxity, broad digits, brachycephaly, small mouth, prominent eyes, short or webbed neck, congenital heart defects and mild developmental delay. Linkeropathies are due to enzymatic defects in the synthesis of the common linker region that joins the core proteins to their glycosaminoglycan (GAG) side chains. The enzyme glucuronyltransferase 1, encoded by B3GAT3, adds the last four saccharides comprising the linker region. Mutations in B3GAT3 have been reported in two unrelated families with the same homozygous mutation (c.830G>A, p.Arg277Gln). We report on a patient with a novel homozygous B3GAT3 (c.667G>A, p.Gly223Ser) mutation and a history of multiple fractures, blue sclerae, and glaucoma. Our patient was a 12-month-old boy born to consanguineous parents and, like previously reported patients, he had bilateral radio-ulnar synostosis, severe osteopenia, an increased gap between first and second toes, bilateral club feet, and atrial and ventricular septal defects. He had the additional features of bilateral glaucoma, hypertelorism, upturned nose with anteverted nares, a small chest, a diaphragmatic hernia, multiple fractures, arachnodactyly, overlapping fingers with ulnar deviation, lymphedema, hypotonia, hearing loss, and perinatal cerebral infarction with bilateral supra- and infratentorial subdural hematomas. We highlight the extended phenotypic range of B3GAT3 mutations and a provide comparative overview of the phenotypic features of the linkeropathies associated with mutations in XYLT1, B4GALT7, B3GALT6, and B3GAT3.
Topics: Fractures, Multiple; Genetic Testing; Glucuronosyltransferase; Homozygote; Humans; Infant; Infant, Newborn; Male; Mutation; Phenotype; Radiography; Syndrome
PubMed: 26086840
DOI: 10.1002/ajmg.a.37209