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Korean Journal of Pediatrics Jun 2011Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial...
Distal duplication, or trisomy 15q, is an extremely rare chromosomal disorder characterized by prenatal and postnatal overgrowth, mental retardation, and craniofacial malformations. Additional abnormalities typically include an unusually short neck, malformations of the fingers and toes, scoliosis and skeletal malformations, genital abnormalities, particularly in affected males, and, in some cases, cardiac defects. The range and severity of symptoms and physical findings may vary from case to case, depending upon the length and location of the duplicated portion of chromosome 15q. Most reported cases of duplication of the long arm of chromosome 15 frequently have more than one segmental imbalance resulting from unbalanced translocations involving chromosome 15 and deletions in another chromosome, as well as other structural chromosomal abnormalities. We report a female newborn with a de novo duplication, 15q24-q26.3, showing intrauterine overgrowth, a narrow asymmetric face with down-slanting palpebral fissures, a large, prominent nose, and micrognathia, arachnodactyly, camptodactyly, congenital heart disease, hydronephrosis, and hydroureter. Chromosomal analysis showed a 46,XX,inv(9)(p12q13),dup(15)(q24q26.3). Array comparative genomic hybridization analysis revealed a gain of 42 clones on 15q24-q26.3. This case represents the only reported patient with a de novo 15q24-q26.3 duplication that did not result from an unbalanced translocation and did not have a concomitant monosomic component in Korea.
PubMed: 21949522
DOI: 10.3345/kjp.2011.54.6.267 -
The Journal of Biological Chemistry Mar 1965
Topics: Animals; Arachnodactyly; Cartilage; Cattle; Chemical Phenomena; Chemical Precipitation; Chemistry; Chemistry Techniques, Analytical; Cornea; Electrophoresis; Hyaluronoglucosaminidase; Intervertebral Disc; Keratan Sulfate; Marfan Syndrome; Peptide Hydrolases; Polysaccharides; Research; Serine; Sharks; Spectrum Analysis; Threonine
PubMed: 14284693
DOI: No ID Found -
Dermatology Online Journal Aug 2011Professor Salim Haim (1919-1983) was a well-known dermatologist. In 1965, Dr. Haim and Dr. Munk, a radiologist, reported a rare congenital type of genodermatosis, later...
Professor Salim Haim (1919-1983) was a well-known dermatologist. In 1965, Dr. Haim and Dr. Munk, a radiologist, reported a rare congenital type of genodermatosis, later known as Haim-Munk syndrome. This syndrome is characterized by palmoplantar keratosis, pes planus, onychogryphosis, periodontitis, arachnodactyly, and acroosteolysis. This report discusses Haim and Haim-Munk syndrome.
Topics: Acro-Osteolysis; Dermatology; History, 20th Century; Humans; Iraq; Papillon-Lefevre Disease
PubMed: 21906495
DOI: No ID Found -
ELife Jan 2021Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These...
Shprintzen-Goldberg syndrome (SGS) is a multisystemic connective tissue disorder, with considerable clinical overlap with Marfan and Loeys-Dietz syndromes. These syndromes have commonly been associated with enhanced TGF-β signaling. In SGS patients, heterozygous point mutations have been mapped to the transcriptional co-repressor SKI, which is a negative regulator of TGF-β signaling that is rapidly degraded upon ligand stimulation. The molecular consequences of these mutations, however, are not understood. Here we use a combination of structural biology, genome editing, and biochemistry to show that SGS mutations in SKI abolish its binding to phosphorylated SMAD2 and SMAD3. This results in stabilization of SKI and consequently attenuation of TGF-β responses, both in knockin cells expressing an SGS mutation and in fibroblasts from SGS patients. Thus, we reveal that SGS is associated with an attenuation of TGF-β-induced transcriptional responses, and not enhancement, which has important implications for other Marfan-related syndromes.
Topics: Arachnodactyly; Craniosynostoses; DNA-Binding Proteins; Female; Humans; Male; Marfan Syndrome; Mutation; Proto-Oncogene Proteins; Signal Transduction; Transforming Growth Factor beta
PubMed: 33416497
DOI: 10.7554/eLife.63545 -
Child and Adolescent Psychiatry and... 2017Minor physical anomalies (MPAs) are subtle anatomical deviations in one's appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in...
BACKGROUND
Minor physical anomalies (MPAs) are subtle anatomical deviations in one's appearance and may suggest altered embryogenesis. MPAs have been shown to be more common in neurodevelopmental disorders (NDDs) compared with typical development. Still, further studies are needed on MPAs in NDDs, especially using twins to adjust for confounding familial factors.
METHODS
Clinical assessments were conducted on 116 twins (61 NDD, 55 controls) from 51 monozygotic and 7 dizygotic pairs to examine MPAs and their association with DSM-5 defined NDDs. Additionally, the relationship between the number of MPAs within twins by zygosity was investigated.
RESULTS
Within the cohort sample, a specific association was found between MPAs and autism spectrum disorder (ASD) diagnosis (crude odds ratio = 1.29, p = .047; adjusted odds ratios = 1.26-1.33, adjusted p values = .032-.073) and autistic traits (crude β = 3.02, p = .002; adjusted β = 2.28, p = .019), but not NDDs in general or ADHD, nor within-pairs. Identified MPAs in ASD included overweight, hypermobility, pes planus, straight eyebrows, vision impairment, arachnodactyly/long toes, long eyelashes, and microtia. The number of MPAs within all monozygotic pairs was highly correlated (r = .88, p < .001).
CONCLUSION
MPAs are more frequent in participants with ASD and may be influenced by genetics. The value of MPAs for (early) detection should be further explored, as they might index individuals at increased risk for ASD in particular.
PubMed: 29209412
DOI: 10.1186/s13034-017-0195-y -
Neurology. Genetics Aug 2021To determine whether mutations reported for can cause mixed neurodevelopmental disorders, we performed both functional studies on variant pathogenicity and ZDHHC15...
OBJECTIVE
To determine whether mutations reported for can cause mixed neurodevelopmental disorders, we performed both functional studies on variant pathogenicity and ZDHHC15 function in animal models.
METHODS
We examined protein function of 4 identified variants in ZDHHC15 in a yeast complementation assay and locomotor defects of loss-of-function genotypes in a model.
RESULTS
Although we assessed multiple patient variants, only 1 (p.H158R) affected protein function. We report a patient with a diagnosis of hypotonic cerebral palsy, autism, epilepsy, and intellectual disability associated with this bona fide damaging X-linked variant. Features include tall forehead with mild brachycephaly, down-slanting palpebral fissures, large ears, long face, facial muscle hypotonia, high-arched palate with dental crowding, and arachnodactyly. The patient had mild diminished cerebral volume, with left-sided T2/FLAIR hyperintense periatrial ovoid lesion. We found that loss-of-function mutations in orthologs of this gene cause flight and coordinated movement defects in .
CONCLUSIONS
Our findings support a functional expansion of this gene to a role in motor dysfunction. Although mutations represent a rare cause of neurodevelopmental disability, candidate variants need to be carefully assessed before pathogenicity can be determined.
PubMed: 34345675
DOI: 10.1212/NXG.0000000000000602 -
BMC Medical Genomics Feb 2022Linkeropathies refers to a series of extremely rare hereditary connective tissue diseases affected by various glycosyltransferases in the biosynthesis of proteoglycans.... (Review)
Review
BACKGROUND
Linkeropathies refers to a series of extremely rare hereditary connective tissue diseases affected by various glycosyltransferases in the biosynthesis of proteoglycans. We report for the first time two heterozygous variants of B3GAT3 in a Chinese infant, in whom Marfan syndrome was suspected at birth.
CASE PRESENTATION
A 2-month-old boy from a non-consanguineous Chinese family without a family history presented severe phenotypes of joint dislocation, obvious flexion contractures of the elbow, arachnodactyly with slightly adducted thumbs, cranial dysplasia, foot abnormalities and aortic root dilation; Marfan syndrome was suspected at birth. Our patient was the youngest, at the age of 2 months, to experience aortic root dilation. Two B3GAT3 variants, NM_012200.2, c.752T>C, p.V251A and c.47C>A, p.S16*, with heterozygosity were identified in the patient by whole-exome sequencing; the variants were inherited from his parents. During close follow-up, significant changes in the cranial profile and obvious external hydrocephalus were present at the age of 7 months, which differs from previously reported cases.
CONCLUSION
We diagnosed a patient with congenital heart defects at an early age with a B3GAT3-related disorder instead of Marfan syndrome and expanded the spectrum of B3GAT3-related disorders. We also provide a literature review of reported B3GAT3 cases; for at least one of the variants, this is the first report of genotype-phenotype correlations in individuals with cardiovascular defects being related to the acceptor substrate-binding subdomain of B3GAT3.
Topics: Genetic Association Studies; Glucuronosyltransferase; Heterozygote; Humans; Phenotype; Exome Sequencing
PubMed: 35151321
DOI: 10.1186/s12920-022-01160-9 -
Philosophical Transactions of the Royal... Oct 2023Over 240 million people are infected with schistosomiasis. Detecting eggs in stool using Kato-Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity....
Over 240 million people are infected with schistosomiasis. Detecting eggs in stool using Kato-Katz thick smears (Kato-Katzs) is highly specific but lacks sensitivity. The urine-based point-of-care circulating cathodic antigen test (POC-CCA) has higher sensitivity, but issues include specificity, discrepancy between batches and interpretation of trace results. A semi-quantitative G-score and latent class analyses making no assumptions about trace readings have helped address some of these issues. However, intra-sample and inter-sample variation remains unknown for POC-CCAs. We collected 3 days of stool and urine from 349 and 621 participants, from high- and moderate-endemicity areas, respectively. We performed duplicate Kato-Katzs and one POC-CCA per sample. In the high-endemicity community, we also performed three POC-CCA technical replicates on one urine sample per participant. Latent class analysis was performed to estimate the relative contribution of intra- (test technical reproducibility) and inter-sample (day-to-day) variation on sensitivity and specificity. Within-sample variation for Kato-Katzs was higher than between-sample, with the opposite true for POC-CCAs. A POC-CCA G3 threshold most accurately assesses individual infections. However, to reach the WHO target product profile of the required 95% specificity for prevalence and monitoring and evaluation, a threshold of G4 is needed, but at the cost of reducing sensitivity. This article is part of the theme issue 'Challenges and opportunities in the fight against neglected tropical diseases: a decade from the London Declaration on NTDs'.
Topics: Humans; Animals; Uganda; Point-of-Care Systems; Reproducibility of Results; Schistosoma mansoni; Neglected Diseases
PubMed: 37598698
DOI: 10.1098/rstb.2022.0275 -
Clinical Medicine Insights. Arthritis... 2013A leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly...
BACKGROUND
A leptosomic body type is tall and thin with long hands. Marfanoid features may be familial in nature or pathological, as occurs in congenital contractual arachnodactyly (Beal's syndrome) and Shprintzen-Goldberg syndrome mimicking some of the changes of Marfan syndrome, although not accompanied by luxation of lens and dissecting aneurysm of aorta.
METHODS
In this article we collected eight patients who were consistent with the diagnosis of Marfan syndrome via phenotypic and genotypic characterization.
RESULTS
Our patients manifested a constellation of variable presentations of musculo-skeletal abnormalities ranging from developmental dysplasia of the hip, protrusio acetabuli, leg length inequality, patellar instability, scoliosis, to early onset osteoarthritis. Each abnormality has been treated accordingly.
CONCLUSION
This is the first paper which includes the diagnosis and the management of the associated musculo-skeletal abnormalities in patients with Marfan syndrome, stressing that patients with Marfan syndrome are exhibiting great variability in the natural history and the severity of musculo-skeletal abnormalities.
PubMed: 23399831
DOI: 10.4137/CMAMD.S10279 -
BMC Medical Genomics Jul 2022Osteogenesis imperfecta (OI) is the most common monogenic disease of the skeletal system and is usually caused by mutations in the COL1A1 or COL1A2 genes. Congenital...
BACKGROUND
Osteogenesis imperfecta (OI) is the most common monogenic disease of the skeletal system and is usually caused by mutations in the COL1A1 or COL1A2 genes. Congenital contractural arachnodactyly syndrome (CCA) is an autosomal dominant hereditary disease of connective tissue. To date, the FBN2 gene is the only gene reported to cause CCA. Researchers found that COL1A2 and FBN2 are both involved in the extracellular matrix organization pathway. These findings suggest that these two genes play an important role in a similar mechanism and may trigger a synergistic effect.
METHODS
Trio-whole-exome sequencing (Trio-WES) was performed to analyse the underlying genetic cause of a proband with OI in a Chinese family. Sanger sequencing was used to validate the mutations in 3 members of the family with OI with varying degrees of severity of skeletal abnormalities and the members with no clinical signs.
RESULT
A c.3304G > C mutation in the COL1A2 gene (p.Gly1102Arg) and a novel c.4108G > T mutation in the FBN2 gene (p.Glu1370*) were detected in the proband, an affected member of the family. The affected individuals with both mutations present a more severe phenotype, while affected individuals present a milder phenotype if only the mutation in COL1A2 is detected (c.3304G > C). The unaffected individual in this family did not have any mutations in the COL1A2 gene or FBN2 gene.
CONCLUSION
Our study is the first clinical report to indicate that patients carrying concomitant mutations in both the COL1A2 and FBN2 genes may present with more severe skeletal abnormalities. Furthermore, our study suggests the possibility of synergistic effects between the COL1A2 and FBN2 genes.
Topics: Arachnodactyly; Collagen Type I; Contracture; Fibrillin-2; Humans; Mutation; Osteogenesis Imperfecta; Phenotype
PubMed: 35804365
DOI: 10.1186/s12920-022-01296-8