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American Journal of Human Genetics Dec 1998Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian...
Turner syndrome is the complex human phenotype associated with complete or partial monosomy X. Principle features of Turner syndrome include short stature, ovarian failure, and a variety of other anatomic and physiological abnormalities, such as webbed neck, lymphedema, cardiovascular and renal anomalies, hypertension, and autoimmune thyroid disease. We studied 28 apparently nonmosaic subjects with partial deletions of Xp, in order to map loci responsible for various components of the Turner syndrome phenotype. Subjects were carefully evaluated for the presence or absence of Turner syndrome features, and their deletions were mapped by FISH with a panel of Xp markers. Using a statistical method to examine genotype/phenotype correlations, we mapped one or more Turner syndrome traits to a critical region in Xp11.2-p22.1. These traits included short stature, ovarian failure, high-arched palate, and autoimmune thyroid disease. The results are useful for genetic counseling of individuals with partial monosomy X. Study of additional subjects should refine the localization of Turner syndrome loci and provide a rational basis for exploration of candidate genes.
Topics: Adolescent; Adult; Autoantibodies; Body Height; Centromere; Child; Child, Preschool; Chromosome Deletion; Chromosome Mapping; Cohort Studies; DNA Methylation; Dosage Compensation, Genetic; Elbow; Female; Genetic Linkage; Genetic Markers; Genotype; Humans; In Situ Hybridization, Fluorescence; Infant; Middle Aged; Palate; Primary Ovarian Insufficiency; Thyroid Diseases; Turner Syndrome; X Chromosome
PubMed: 9837829
DOI: 10.1086/302152 -
Annals of Medical and Health Sciences... 2015The present report describes a case of Noonan's syndrome from a dental viewpoint. Noonan syndrome is an autosomal dominant multisystem disorder. Congenital heart...
The present report describes a case of Noonan's syndrome from a dental viewpoint. Noonan syndrome is an autosomal dominant multisystem disorder. Congenital heart deformities, short stature, thoracic deformities, short neck with webbing, hypertelorism, and malocclusions are some of the frequently observed clinical features. Atypical dental anomalies such as multiple unerupted permanent teeth, multiple submerged and retained deciduous teeth, and supernumerary teeth were found in the present case. Oral prophylaxis and preventive resin restorations were done following which the supernumerary teeth were extracted. 54, 55, 64, 65, 74, 75 and 84 were extracted after orthodontic consultation to facilitate the eruption of permanent teeth. The patient is undergoing fixed orthodontic therapy for forced eruption of unerupted permanent teeth. General dentists should correlate dental anomalies with other systemic features in the diagnosis of such syndromes because of the variability in presentation and the need for multidisciplinary care.
PubMed: 26229724
DOI: 10.4103/2141-9248.160190 -
Journal of Craniovertebral Junction &... 2021We present a report of two patients having the association of omovertebra, Sprengel's deformity of the shoulder and Klippel-Feil abnormality with craniovertebral...
We present a report of two patients having the association of omovertebra, Sprengel's deformity of the shoulder and Klippel-Feil abnormality with craniovertebral junctional instability. Our literature survey did not locate any report of such association. Significance of bone alterations is analyzed. Two young patients presented with neck pain, torticollis, webbed neck, and spastic quadriparesis. In both patients, the investigations revealed basilar invagination, Klippel-Feil abnormality and Sprengel's deformity of the shoulder. Apart from these relatively common associations, both the patients had omovertebral bone that extended from the transverse process of C5 vertebra to scapula. Following atlantoaxial stabilization surgery, the patients rapidly recovered from all symptoms. Musculoskeletal abnormalities at the craniovertebral junction that include Klippel-Feil abnormality, Sprengel's shoulder, and omovertebra are secondary alterations to primary atlantoaxial instability.
PubMed: 33850390
DOI: 10.4103/jcvjs.JCVJS_7_21 -
Journal of Medical Genetics Feb 1976A pair of monozygotic, adolescent twins is discordant for sex. The phenotypic female twin has chromosome constitution of 46, XY/45, X. She displays many signs of...
A pair of monozygotic, adolescent twins is discordant for sex. The phenotypic female twin has chromosome constitution of 46, XY/45, X. She displays many signs of Turner's syndrome, including typical facies, webbed neck, malformed left kidney, high plasma gonadotropins, and streak ovaries. However, her height is 154 cm which exceeds the height usually reported in Turner's syndrome. The male twin has a karyotype of 46, XY and normal sexual development. Only two other reports of pairs of monozygotic twins of opposite sex have been published.
Topics: Adolescent; Blood Group Antigens; Chromosomes; Diseases in Twins; Female; Humans; Karyotyping; Male; Mosaicism; Phenotype; Pregnancy; Sex Chromatin; Sex Chromosome Aberrations; Sex Chromosomes; Sex Determination Analysis; Turner Syndrome; Twins; Twins, Monozygotic
PubMed: 944787
DOI: 10.1136/jmg.13.1.64 -
Singapore Medical Journal May 2008Turner syndrome affects about one in 2,000 live-born females, and the wide range of somatic features indicates that a number of different X-located genes are responsible...
INTRODUCTION
Turner syndrome affects about one in 2,000 live-born females, and the wide range of somatic features indicates that a number of different X-located genes are responsible for the complete phenotype. This retrospective study highlights the Turner syndrome cases confirmed through cytogenetic analysis at the Human Genome Centre of Universiti Sains Malaysia, from 2001 to 2006.
METHODS
Lymphocyte cultures were set up using peripheral blood samples, chromosomes were prepared, G-banded, karyotyped and analysed in accordance to guidelines from the International System for Human Cytogenetic Nomenclature.
RESULTS
The various karyotype patterns observed were 45,X; 46,X,i, (Xq); 45,X/45,X,+mar; 45,X/46,X,i,(Xq) and 45,X/46,XY. The mean age of our patients with Turner syndrome was 21 years, and the most common clinical features encountered in all these patients were short stature (100 percent), primary amenorrhoea (85.7 percent), absence of secondary sexual characteristics (57.1 percent), scanty pubic and axillary hair (50 percent), webbed neck (42.9 percent), wide carrying angle (42.9 percent), rudimentary uterus with bilateral streak ovaries (42.9 percent), underdeveloped breasts (35.7 percent) and wide-spaced nipples (21.4 percent).
CONCLUSION
Even though there is no causal therapy for Turner syndrome, management and treatment are possible for malformations and conditions associated with it. In addition, counselling of the parents and of the patients themselves are necessary. Hence, establishing an early diagnosis, educating and increasing awareness among doctors, and if possible, a prenatal diagnosis, will help in early intervention, genetic counselling and in improving the quality of life in these patients.
Topics: Adolescent; Adult; Child; Humans; Karyotyping; Malaysia; Middle Aged; Retrospective Studies; Turner Syndrome
PubMed: 18465051
DOI: No ID Found -
European Journal of Medical Genetics Feb 2023Noonan syndrome is characterized by variable phenotypic expressivity with characteristic dysmorphic facial features, varying degrees of intellectual disability,...
Noonan syndrome is characterized by variable phenotypic expressivity with characteristic dysmorphic facial features, varying degrees of intellectual disability, developmental delay, short stature, and congenital heart defects in 50-80%. Other findings include a webbed neck, cryptorchidism, coagulation defects and eye abnormalities. Thus far, Noonan syndrome has mainly been attributed to heterozygous pathogenic variants in 10+ different genes, with the rare exception of cases due to biallelic pathogenic variants in LZTR1. Recently, homozygous loss-of-function variants in SPRED2 have been identified as a cause of a recessive Noonan syndrome-like phenotype. We present the phenotypes of two additional patients with homozygosity for a previously unreported loss-of-function variant in SPRED2, thereby adding relevant clinical information about the recently described Noonan syndrome-like SPRED2-related phenotype.
Topics: Humans; Male; Heart Defects, Congenital; Heterozygote; Homozygote; Intellectual Disability; Noonan Syndrome; Phenotype; Repressor Proteins; Transcription Factors
PubMed: 36608738
DOI: 10.1016/j.ejmg.2023.104695 -
Molecular Genetics & Genomic Medicine Mar 2024The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like...
BACKGROUND
The MYH3-associated myosinopathies comprise a spectrum of rare neuromuscular disorders mainly characterized by distal arthrogryposis with or without other features like pterygia and vertebrae fusion. CPSKF1B (contractures, pterygia, and spondylocarpotarsal fusion syndrome1B) is the only known autosomal recessiveMYH3-associated myosinopathy so far, with no more than two dozen cases being reported.
MATERIALS AND METHODS
A boy with CPSKF1B was recruited and subjected to a comprehensive clinical and imaging evaluation. Genetic detection with whole-exome sequencing (WES) was performed on the patient and extended family members to identify the causative variation. A series of in silico and in vitro investigations were carried out to verify the pathogenicity of the two variants of the identified compound heterozygous variation.
RESULTS
The patient exhibited moderate CPSKF1B symptoms including multiarticular contractures, webbed neck, and spondylocarpotarsal fusion. WES detected a compound heterozygous MYH3 variation consisting of two variants, namely NM_002470.4: c.3377A>G; p. (E1126G) and NM_002470.4: c.5161-2A>C. It was indicated that the NM_002470.4: c.3377A>G; p. (E1126G) variant mainly impaired the local hydrogen bond formation and impacted the TGF-B pathway, while the NM_002470.4: c.5161-2A>C variant could affect the normal splicing of pre-mRNA, resulting in the appearance of multiple abnormal transcripts.
CONCLUSIONS
The findings of this study expanded the mutation spectrum of CPSKF1B, provided an important basis for the counseling of the affected family, and also laid a foundation for the functional study of MYH3 mutations.
Topics: Humans; Male; Arthrogryposis; Conjunctiva; Contracture; Family; Pterygium
PubMed: 38444278
DOI: 10.1002/mgg3.2401 -
Balkan Journal of Medical Genetics :... Jun 2020A 28-year-old woman underwent amniocentesis at 18 weeks' gestation upon detection of increased fetal nuchal fold and parietal cephalocele on the second trimester...
A 28-year-old woman underwent amniocentesis at 18 weeks' gestation upon detection of increased fetal nuchal fold and parietal cephalocele on the second trimester ultrasound examination. Prenatal microarray showed a unbalanced translocation resulting in a gain in 6q and loss in 18p. A female infant was delivered at 38 weeks' gestation. At birth, cephalocele and webbed neck were noted as major dysmorphic features. The case presented here shows how a combination of different genetic studies is used to accurately elucidate a chromosomal anomaly in a prenatal setting.
PubMed: 32953417
DOI: 10.2478/bjmg-2020-0014 -
American Journal of Human Genetics Jan 2008Multiple pterygium syndromes (MPS) comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and...
Multiple pterygium syndromes (MPS) comprise a group of multiple congenital anomaly disorders characterized by webbing (pterygia) of the neck, elbows, and/or knees and joint contractures (arthrogryposis). MPS are phenotypically and genetically heterogeneous but are traditionally divided into prenatally lethal and nonlethal (Escobar) types. Previously, we and others reported that recessive mutations in the embryonal acetylcholine receptor g subunit (CHRNG) can cause both lethal and nonlethal MPS, thus demonstrating that pterygia resulted from fetal akinesia. We hypothesized that mutations in acetylcholine receptor-related genes might also result in a MPS/fetal akinesia phenotype and so we analyzed 15 cases of lethal MPS/fetal akinesia without CHRNG mutations for mutations in the CHRNA1, CHRNB1, CHRND, and rapsyn (RAPSN) genes. No CHRNA1, CHRNB1, or CHRND mutations were detected, but a homozygous RAPSN frameshift mutation, c.1177-1178delAA, was identified in a family with three children affected with lethal fetal akinesia sequence. Previously, RAPSN mutations have been reported in congenital myasthenia. Functional studies were consistent with the hypothesis that whereas incomplete loss of rapsyn function may cause congenital myasthenia, more severe loss of function can result in a lethal fetal akinesia phenotype.
Topics: Abnormalities, Multiple; Amino Acid Sequence; Arthrogryposis; Base Sequence; Child; Fetal Diseases; Humans; Molecular Sequence Data; Muscle Proteins; Receptors, Cholinergic; Receptors, Nicotinic; Syndrome
PubMed: 18179903
DOI: 10.1016/j.ajhg.2007.09.016 -
The Kurume Medical Journal 2011Large numbers of patients with deletions of the long arm of chromosome 13 have been described. However, only a few instances have been reported of monosomy 13/r(13)...
Large numbers of patients with deletions of the long arm of chromosome 13 have been described. However, only a few instances have been reported of monosomy 13/r(13) mosaicism. A 31-year-old Japanese woman underwent an ultrasound tomographic screening, which detected a fetus with a nuchal translucency (NT) of >5.8mm, indicating an increased risk of fetal chromosomal abnormality. An amniocentesis (AC) was performed, and the karyotype was 46,XX,r(13)(p11q33)[18] / 45XX[12]. Ultrasound showed echogenic skin edema. Phenotype of the fetus after delivery revealed some anomalies, including hyponasal bridge, hypertelorism, ambiguous genitalia with huge clitoris, low-set ear, neck edema and webbing.Deletion of the long arm of chromosome 13 is associated with a wide spectrum of abnormalities, including retinoblastoma, mental and growth retardation, brain malformations, heart defects, distal limb deformities, and digestive, urogenital, and other abnormalities. The present case, however, had anomalies which were too faint to be detected by ultrasound tomography. Prenatal diagnosis of deletion 13q syndrome is rare. A number of reports have documented an association between increased NT and chromosomal defects. Ultrasound did not identify any major anomaly in this case, however amniocentesis was able to detect this rare abnormality.
Topics: Adult; Chromosome Deletion; Chromosome Disorders; Chromosomes, Human, Pair 13; Female; Humans; Karyotyping; Nuchal Translucency Measurement; Pregnancy
PubMed: 23047142
DOI: 10.2739/kurumemedj.58.127