22q11.2 Microduplications: Two Clinical Reports Compared with Similar Cases from the Literature.
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ABSTRACT:
SUBMITTER: Oyetunji A
PROVIDER: S-EPMC7375851 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:The chromosome region 22q11.2 has long been recognized to be susceptible to genomic rearrangement. More recently, this genomic instability has been shown to extend distally (involving LCR22E-H) to the commonly deleted/duplicated region. To date, 21 index cases with 'distal' 22q11.2 duplications have been reported. We report on the clinical and molecular characterization of 16 individuals with distal 22q11.2 duplications identified by DNA microarray analysis. Two of the individuals have been partly described previously. The clinical phenotype varied among the patients in this study, although the majority displayed various degrees of developmental delay and speech disturbances. Other clinical features included behavioral problems, hypotonia, and dysmorphic facial features. Notably, none of the patients was diagnosed with a congenital heart defect. We found a high degree of inherited duplications. Additional copy number changes of unclear clinical significance were identified in 5 of our patients, and it is possible that these may contribute to the phenotypic expression in these patients as has been suggested recently in a 2-hit 'digenic' model for 16p12.1 deletions. The varied phenotypic expression and incomplete penetrance observed for distal 22q11.2 duplications makes it exceedingly difficult to ascribe pathogenicity for these duplications. Given the observed enrichment of the duplication in patient samples versus healthy controls, it is likely that distal 22q11.2 duplications represent a susceptibility/risk locus for speech and mild developmental delay.
| S-EPMC3214948 | biostudies-literature
Project description:Chromosome 22q11.2 microdeletion syndrome is due to microdeletion of 22q11.2 region of chromosome 22. It is a common microdeletion syndrome however mosaic cases are very rare and reported only few previous occasions. In this report we describe two unrelated male children with clinical features consistent with 22q11.2 microdeletion syndrome characterized by cardiac defect, facial dysmorphism and developmental deficiency. One of the cases also had trigonocephaly. Interphase & metaphase FISH with 22q11.2 probe demonstrated mosaicism for hemizygous deletion of 22q11.2 region. Mosaicism is also observed in buccal cells as well as urine cells. Parents were without any deletion. These two cases represent rare cases of mosaic 22q11.2 microdeletion syndrome.
| S-EPMC2527005 | biostudies-literature
Project description:Abetalipoproteinemia (ABL, OMIM 200100) is a rare, autosomal recessive disorder, characterized by fat malabsorption, acanthocytosis and hypocholesterolemia in infancy. Later in life, deficiency of fat-soluble vitamins is associated with development of atypical retinitis pigmentosa, coagulopathy, posterior column neuropathy and myopathy. ABL results from mutations in the gene encoding the large subunit of microsomal triglyceride transfer protein (MTP; OMIM 157147). To date at least 33 MTP mutations have been identified in 43 ABL patients. We describe the clinical progress of two patients, both currently in the fifth decade of life, who were diagnosed with ABL as children and were treated with high oral doses of fat soluble vitamins, including vitamin E over the last three decades. Treatment appears to have been associated with arrest of the neuropathy and other complications in both patients. Because pharmacologic inhibition of MTP is being developed as a novel approach to reduce plasma cholesterol for prevention of cardiovascular disease, defining the long-term clinical features of patients with a natural deficiency in MTP might provide some insight into the possible effects of such treatments. We review the range of clinical, biochemical and molecular perturbations in ABL.
| S-EPMC2467409 | biostudies-literature
Project description:BackgroundProteoglycans are large and structurally complex macromolecules which can be found in abundancy in the extracellular matrix and on the surface of all animal cells. Mutations in the genes encoding the enzymes responsible for the formation of the tetrasaccharide linker region between the proteoglycan core protein and the glycosaminoglycan side chains lead to a spectrum of severe and overlapping autosomal recessive connective tissue disorders, collectively coined the 'glycosaminoglycan linkeropathies'.ResultsWe report the clinical findings of two novel patients with a complex linkeropathy due to biallelic mutations in B3GAT3, the gene that encodes glucuronosyltransferase I, which catalyzes the addition of the ultimate saccharide to the linker region. We identified a previously reported c.667G > A missense mutation and an unreported homozygous c.416C > T missense mutation. We also performed a genotype and phenotype-oriented literature overview of all hitherto reported patients harbouring B3GAT3 mutations. A total of 23 patients from 10 families harbouring bi-allelic mutations and one patient with a heterozygeous splice-site mutation in B3GAT3 have been reported. They all display a complex phenotype characterized by consistent presence of skeletal dysplasia (including short stature, kyphosis, scoliosis and deformity of the long bones), facial dysmorphology, and spatulate distal phalanges. More variably present are cardiac defects, joint hypermobility, joint dislocations/contractures and fractures. Seven different B3GAT3 mutations have been reported, and although the number of patients is still limited, some phenotype-genotype correlations start to emerge. The more severe phenotypes seem to have mutations located in the substrate acceptor subdomain of the catalytic domain of the glucuronosyltransferase I protein while more mildly affected phenotypes seem to have mutations in the NTP-sugar donor substrate binding subdomain.ConclusionsLoss-of-function mutations in B3GAT3 are associated with a complex connective tissue phenotype characterized by disproportionate short stature, skeletal dysplasia, facial dysmorphism, spatulate distal phalanges and -to a lesser extent- joint contractures, joint hypermobility with dislocations, cardiac defects and bone fragility. Based on the limited number of reported patients, some genotype-phenotype correlations start to emerge.
| S-EPMC6567438 | biostudies-literature
Project description:RationaleSchaaf-Yang syndrome, a rare imprinted hereditary disease caused by MAGEL2 variants, manifests as developmental delay/intellectual disability, neonatal hypotonia, feeding difficulties, contractures, and autism spectrum disorder.Patient concernsPatient 1 and 2 were infant girls presenting facial dysmorphisms, contractures of interphalangeal joints, neonatal hypotonia, feeding difficulties, congenital heart diseases, and respiratory complications. Besides, Patient 2 presented with delayed psychomotor development.DiagnosisWhole-exome sequencing was performed and heterozygous mutations of the MAGEL2 gene were detected in the patients. They were diagnosed as Schaaf-Yang syndrome.InterventionsThe patients received supportive treatment including mechanical ventilation, parenteral nutrition and gastric tube feeding.OutcomesWhole-exome sequencing revealed de novo heterozygous c.1996dupC pathogenic mutations in the MAGEL2 gene in the 2 patients. They died due to respiratory failure at the age of 20 days and 98 days, respectively.LessonsOur results indicate that MAGEL2 variants can cause congenital heart disease and fatal respiratory complications, broadening the phenotypic spectrum and adding to the fatal cases of Schaaf-Yang syndrome. We highly suggest that the MAGEL2 gene should be added to gene-panels or gene-filters in next-generation sequencing-based diagnostics, which is of great significance for early diagnosis and early intervention of Schaaf-Yang syndrome patients.
| S-EPMC7373511 | biostudies-literature
Project description:Case:We have reported six cases of Crowned dens syndrome (CDS) diagnosed by computed tomography (CT). Presenting cases were three male and three female, aged from 45 to 89 (averaged in 72). Outcome:All cases showed calcification around the dens of axis in CTs. Neck pain in all cases relieved within at least 10 days, treated by non-steroidal anti-inflammatory drugs (NSAIDs) in five cases, and one by acetaminophens. Conclusion:Bouvet et?al. first reported CDS in 1985, as acute pseudogout of the neck, which causes neck pain. CDS is a radioclinical syndrome defined by the radiographic calcifications in a crown-like configuration around the odontoid process, accompanied clinically by acute neck pain, often with neck stiffness, fevers and raised inflammatory markers. CDS is thought to be a rare condition; however, it is frequently misdiagnosed. CDS is an important differential diagnosis in patients presenting with acute neck pain.
| S-EPMC5667384 | biostudies-literature
Project description:We describe six individuals with microdeletions and microduplications in the distal 22q11.2 region detected by microarray. Five of the abnormalities have breakpoints in the low-copy repeats (LCR) in this region and one patient has an atypical rearrangement. Two of the six patients with abnormalities in the region between LCR22 D-E have hearing loss, which has previously been reported only once in association with these abnormalities. We especially note the behavioral/neuropsychiatric problems, including the severity and early onset, in patients with distal 22q11.2 rearrangements. Our patients add to the genotype-phenotype correlations which are still being generated for these chromosomal anomalies.
| S-EPMC4521969 | biostudies-literature
Project description:Immunotherapy is increasingly defining a role in a wide variety of tumours such that as use becomes more ubiquitous, so too will the complications. A relatively rare complication of immunotherapy use is immune-related gastritis. In this case series, we present two cases of immunotherapy-related gastritis from our institution and undertake a comprehensive review and analysis of the literature around this less common adverse event.
| S-EPMC8274081 | biostudies-literature
Project description:BACKGROUND: Painful limbs/moving extremities is a relatively rare condition characterized by aching pain in one limb and involuntary movement in the affected fingers or toes. Its pathomechanism is unknown. We report two patients with painful limbs/moving extremities. In one patient with a painful arm and moving fingers, the symptoms were resolved after surgery. CASE DESCRIPTIONS: Patient 1 was a 36-year-old man with a painful arm and moving fingers. Treatment with administration of analgesics was not effective. Postmyelographic CT showed stenosis of the right C5/C6 foramen attributable to cervical spondylosis and a defect of the contrast material at the foramen. He was treated with cervical foraminotomy. Patient 2 was a 26-year-old woman with a painful leg and moving toes. The pain and involuntary movement appeared 2 weeks after discectomy at L5/S1. Lumbar MRI and myelography showed no indications of nerve root compression. She was treated with a lumbar nerve root block. The pain and involuntary movement completely disappeared in both patients after treatment. LITERATURE REVIEW: Numerous studies report treatments for painful limbs/moving extremities, but few report successful treatment. Recently, botulinum toxin A injection and epidural spinal cord stimulation have been used and are thought to benefit this condition. Successful surgical treatment previously was reported for only one patient. PURPOSES AND CLINICAL RELEVANCE: If imaging indicates compression of nerve tissue, we believe surgical decompression should be considered for patients with painful limbs/moving extremities who do not respond to nonoperative treatment.
| S-EPMC2974875 | biostudies-other
Project description:RationaleWiskott-Aldrich syndrome (WAS) is a rare X-linked recessive disease characterized by thrombocytopenia, small platelets, eczema, immunodeficiency, and an increased risk of autoimmunity and malignancies. X-linked thrombocytopenia (XLT), the milder phenotype of WAS, is always limited to thrombocytopenia with absent or slight infections and eczema. Here, we illustrated the clinical and molecular characteristics of 2 unrelated patients with WAS from Chinese minorities.Patient concernsPatient 1, a 13-day-old male newborn of the Chinese Lahu minority, showed a classic WAS phenotype, including thrombocytopenia, small platelets, buttock eczema, and recurrent infections. Patient 2, an 8-year-and 8-month-old boy of the Chinese Zhuang minority, presented an XLT phenotype without eczema and repeated infections.DiagnosisNext-generation sequencing was performed to investigate the genetic variations. Flow cytometry was used to quantify the expression of WAS protein and analyze the lymphocyte subsets. A novel frameshift WAS mutation (c.927delC, p.Q310Rfs∗135) and a known nonsense WAS mutation (c.1090C>T, p.R364X) were identified in Patient 1 and Patient 2, respectively. Both patients were confirmed to have WAS protein deficiency, which was more severe in Patient 1. Meanwhile, the analysis of lymphocyte subsets revealed an abnormality in Patient 1, but not in Patient 2. Combined with the above clinical data and genetic characteristics, Patient 1 and Patient 2 were diagnosed as classic WAS and XLT, respectively. In addition, many miliary nodules were accidentally found in abdominal cavity of Patient 2 during appendectomy. Subsequently, Patient 2 was confirmed with pulmonary and abdominal tuberculosis through further laboratory and imaging examinations. To our knowledge, there have been only a few reports about WAS/XLT with tuberculosis.InterventionsBoth patients received anti-infection therapy, platelet transfusions, and intravenous immunoglobulins. Moreover, Patient 2 also received antituberculosis treatment with ethambutol and amoxicillin-clavulanate.OutcomesThe clinical symptoms and hematological parameters of these 2 patients were significantly improved. Regrettably, both patients discontinued the treatment for financial reasons.LessonsOur report expands the pathogenic mutation spectrum of WAS gene and emphasizes the importance of molecular genetic testing in diagnosing WAS. Furthermore, researching and reporting rare cases of WAS from different populations will facilitate diagnosis and treatment of this disease.
| S-EPMC8078428 | biostudies-literature