Case Reports in Genetics最新文献

{"title":"Characterization of a Pathogenic Variant in the ABCD1 Gene Through Protein Molecular Modeling.","authors":"John E Richter,&nbsp;Charitha Vadlamudi,&nbsp;Sarah K Macklin,&nbsp;Ayesha Samreen,&nbsp;Haytham Helmi,&nbsp;Daniel Broderick,&nbsp;Ahmed N Mohammad,&nbsp;Stephanie L Hines,&nbsp;Jay A VanGerpen,&nbsp;Paldeep S Atwal,&nbsp;Thomas R Caulfield","doi":"10.1155/2020/3256539","DOIUrl":"https://doi.org/10.1155/2020/3256539","url":null,"abstract":"<p><strong>Background: </strong>The ATP-binding cassette, subfamily D, member 1 (ABCD1) protein is a peroxisomal half-transporter that allows for very long chain fatty acid (VLCFA) degradation. Pathogenic variants of <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Methods: </strong>A newly characterized and suspected pathogenic variant in <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Results: </strong>A case of adult onset adrenomyeloneuropathy (AMN) and a novel <i>ABCD1</i> cause VLCFAs to build up in various tissues and bodily fluids, resulting in a disorder called X-linked adrenoleukodystrophy (X-ALD). This disorder is most commonly marked by adrenocortical insufficiency and high VLCFA concentration, and has varying levels of neurological involvement depending on phenotype. For example, the Addison-only form of X-ALD has no neurological impact, while the cerebral form of X-ALD often causes severe sensory loss, motor function impairment, cognitive decline, and death.</p><p><strong>Conclusions: </strong>Data fusion from multiple sources was combined in a comprehensive approach yielding an enriched assessment of the patient's disease and prognosis. Molecular modeling was performed on the variant to better characterize its clinical significance and confirm pathogenicity.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/3256539","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37635538","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Candidate Genes Associated with Delayed Neuropsychomotor Development and Seizures in a Patient with Ring Chromosome 20.","authors":"Thiago Corrêa, Amanda Cristina Venâncio, Marcial Francis Galera, Mariluce Riegel","doi":"10.1155/2020/5957415","DOIUrl":"10.1155/2020/5957415","url":null,"abstract":"<p><p>Ring chromosome 20 (r20) is characterized by intellectual impairment, behavioral disorders, and refractory epilepsy. We report a patient presenting nonmosaic ring chromosome 20 followed by duplication and deletion in 20q13.33 with seizures, delayed neuropsychomotor development and language, mild hypotonia, low weight gain, and cognitive deficit. Chromosomal microarray analysis (CMA) enabled us to restrict a chromosomal segment and thus integrate clinical and molecular data with systems biology. With this approach, we were able to identify candidate genes that may help to explain the consequences of deletions in 20q13.33. In our analysis, we observed five hubs (ARFGAP1, HELZ2, COL9A3, PTK6, and EEF1A2), seven bottlenecks (CHRNA4, ARFRP1, GID8, COL9A3, PTK6, ZBTB46, and SRMS), and two H-B nodes (PTK6 and COL9A3). The candidate genes may play an important role in the developmental delay and seizures observed in r20 patients. Gene ontology included microtubule-based movement, nucleosome assembly, DNA repair, and cholinergic synaptic transmission. Defects in these bioprocesses are associated with the development of neurological diseases, intellectual disability, neuropathies, and seizures. Therefore, in this study, we can explore molecular cytogenetic data, identify proteins through network analysis of protein-protein interactions, and identify new candidate genes associated with the main clinical findings in patients with 20q13.33 deletions.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6995492/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37665018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Behçet Disease-Like Symptoms with a Novel COPA Mutation","authors":"E. Anderson, J. Hatch, J. Cardinal, D. Langguth, D. Coman","doi":"10.1155/2020/8414857","DOIUrl":"https://doi.org/10.1155/2020/8414857","url":null,"abstract":"COPA syndrome is a recently described autosomal dominant disorder with key immune dysregulation caused by defects within the COPA gene. These mutations lead to endoplasmic reticulum stress and autoimmune response with upregulation of Th17 cytokines. The clinical phenotype of COPA syndrome primarily comprised pulmonary disease, arthritis, and renal disease secondary to immune dysregulation, with onset of symptoms commonly in the first decade of life. Herein, we describe a family with an attenuated Behcet-like phenotype of COPA syndrome, further expanding the phenotypic understanding of this syndrome.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"89422505","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromosome 16p13.3 Contiguous Gene Deletion Syndrome including the <i>SLX4</i>, <i>DNASE1</i>, <i>TRAP1</i>, and <i>CREBBP</i> Genes Presenting as a Relatively Mild Rubinstein-Taybi Syndrome Phenotype: A Case Report of a Saudi Boy.","authors":"Mohammad M Al-Qattan,&nbsp;Zuhair A Rahbeeni,&nbsp;Zuhair N Al-Hassnan,&nbsp;Abdulaziz Jarman,&nbsp;Atif Rafique,&nbsp;Nehal Mahabbat,&nbsp;Faris A S Alsufayan","doi":"10.1155/2020/6143050","DOIUrl":"https://doi.org/10.1155/2020/6143050","url":null,"abstract":"<p><p>The classic Rubinstein-Taybi syndrome Type 1 (RSTS1, OMIM 180849) is caused by heterozygous mutations or deletions of the <i>CREBBP</i> gene. Herein, we describe the case of a Saudi boy with chromosome 16p13.3 contiguous gene deletion syndrome (OMIM 610543) including the <i>SLX4</i>, <i>DNASE1</i>, <i>TRAP1</i>, and <i>CREBBP</i> genes, but presenting with a relatively mild RSTS1 syndrome phenotype. Compared with previously reported cases with severe phenotypes associated with 16p13.3 contiguous gene deletions, our patient had partial deletion of the <i>CREBBP</i> gene (with a preserved 5' region), which might explain his relatively mild phenotype.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-01-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/6143050","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37744893","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A Tanzanian Boy with Molecularly Confirmed X-Linked Adrenoleukodystrophy.","authors":"M C J Dekker,&nbsp;A M Sadiq,&nbsp;R Mc Larty,&nbsp;R M Mbwasi,&nbsp;M A A P Willemsen,&nbsp;H R Waterham,&nbsp;B C Hamel","doi":"10.1155/2019/6148425","DOIUrl":"https://doi.org/10.1155/2019/6148425","url":null,"abstract":"<p><p>Adrenoleukodystrophy (ALD) is an X-linked peroxisomal disorder with classical features, which can be also recognised in a low resource setting. It had been described in various populations across the globe, but very few cases have been reported from Africa. In a boy with features of a progressive central nervous system condition and adrenal failure, <i>ABCD1</i> gene screening was performed based on a clinical history and basic radiological features which were compatible with ALD. A common <i>ABCD1</i> mutation was identified in this patient, which is the first report of genetically confirmed ALD in Sub-Saharan Africa. ALD is likely under recognised in those areas where there is no neurologist. This genetic confirmation widens geographical distribution of <i>ABCD1</i>-associated disease, and illustrates recognisability of this disorder, even when encountered in a low-resource environment.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/6148425","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37670691","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Cases of Oculofaciocardiodental (OFCD) Syndrome due to X-Linked BCOR Mutations Presenting with Infantile Hemangiomas: Phenotypic Overlap with PHACE Syndrome.","authors":"T M Morgan,&nbsp;J M Colazo,&nbsp;L Duncan,&nbsp;R Hamid,&nbsp;K M Joos","doi":"10.1155/2019/9382640","DOIUrl":"https://doi.org/10.1155/2019/9382640","url":null,"abstract":"<p><strong>Background: </strong>Oculofaciocardiodental (OFCD) syndrome is due to mutations in BCOR (BCL-6 corepressor). OFCD has phenotypic overlaps with PHACE syndrome (Posterior fossa anomalies, Hemangioma, Arterial anomalies, Cardiac defects, Eye anomalies). Infantile hemangiomas are a key diagnostic criterion for PHACE, but not for OFCD. A previous study reported two cases of infantile hemangiomas in OFCD, but the authors could not exclude chance association.</p><p><strong>Case presentation: </strong>We describe two novel cases of female patients (one initially diagnosed with PHACE syndrome), both of whom had infantile hemangiomas. Ophthalmological findings were consistent with oculofaciocardiodental (OFCD) syndrome. Upon genetic testing, these two females were determined to have X-linked BCOR mutations confirming OFCD syndrome diagnoses.</p><p><strong>Conclusion: </strong>These case reports add support to the hypothesis that infantile hemangiomas may be a feature of OFCD. BCOR may potentially be within a pathway of genes involved in PHACE syndrome and/or in infantile hemangioma formation.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/9382640","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37557942","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Towards New Approaches to Evaluate Dynamic Mosaicism in Ring Chromosome 13 Syndrome.","authors":"Cristian Petter,&nbsp;Lilia Maria Azevedo Moreira,&nbsp;Mariluce Riegel","doi":"10.1155/2019/7250838","DOIUrl":"https://doi.org/10.1155/2019/7250838","url":null,"abstract":"<p><p>Individuals with ring chromosome 13 may show characteristics observed in a deletion syndrome and could present a set of dismorphies along with intellectual disability, according to chromosomal segments involved in the genetic imbalance. Nevertheless, ring anomalies likewise is called \"dynamic mosaicism\", phenomena triggered by the inner instability concerning the ring structure, thus leading to the establishment of different cell clones with secondary aberrations. Phenotypic features, such as growth failure and other anomalies in patients with this condition have been associated with an inherent ring chromosome mitotic instability, while recent studies offer evidence on a role played by the differential loss of genes implicated in development. Here, we observed similar mosaicism rates and specific gene loss profile among three individuals with ring chromosome 13 using GTW-banding karyotype analyses along with FISH and CGH-array approaches. Karyotypes results were: patient 1-r(13)(p13q32.3), patient 2-r(13)(p11q33.3), and patient 3-r(13)(p12q31.1). Array-CGH has revealed qualitative genetic differences among patients in this study and it was elusive in precise chromosomal loss statement, ranging from 13 Mb, 6.8 Mb, and 30 Mb in size. MIR17HG and ZIC2 loss was observed in a patient with digital anomalies, severe growth failure, microcephaly and corpus callosum agenesis while hemizygotic EFNB2 gene loss was identified in two patients, one of them with microphtalmia. According to these findings, it can be concluded that specific hemizygotic loss of genes related to development, more than dynamic mosaicism, may be causative of congenital anomalies shown in patients with ring 13 chromosome.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/7250838","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37574504","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Familial Russell-Silver Syndrome like Phenotype in the PCNA Domain of the <i>CDKN1C</i> Gene, a Further Case.","authors":"A H Sabir,&nbsp;G Ryan,&nbsp;Z Mohammed,&nbsp;J Kirk,&nbsp;N Kiely,&nbsp;M Thyagarajan,&nbsp;T Cole","doi":"10.1155/2019/1398250","DOIUrl":"https://doi.org/10.1155/2019/1398250","url":null,"abstract":"<p><p>We present two half siblings with significant short stature who proved a diagnostic challenge for several years. Radiological findings included subtle epiphyseal changes. The diagnosis was made through whole genome sequencing via the 100,000 genome project. A maternally inherited pathogenic heterozygous <i>CDKN1C</i> variant was found in the PCNA (proliferating cell nuclear antigen) domain. Mutations of the PCNA domain of the <i>CDKN1C</i> gene are known to be associated with IMAGe syndrome thus with adrenal disease, although neither affected patient in our case had evidence of adrenal dysfunction. This report supports the previously reported findings of Russell-Silver syndrome (RSS) like phenotype caused by this unusual mechanism (CDKN1C mutations in the PCNA domain), highlights subtle radiological features not described previously and the phenotypic variability between two affected siblings. Additionally it reminds clinicians of the importance of considering associated adrenal disease/diabetes mellitus for variants within the PCNA domain. Finally it confirms RSS-like disorders should be considered in patients who have epiphyseal or metaphyseal changes and short stature, since CDKN1C PCNA domain mutations can result in this phenotype.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-12-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/1398250","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37574503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Corrigendum to \"Chromosome 3p Inverted Duplication with Terminal Deletion: Second Postnatal Case Report with Additional Clinical Features\".","authors":"Jacquelyn D Riley,&nbsp;Catherine M Stefaniuk,&nbsp;Francine Erenberg,&nbsp;Angelika L Erwin,&nbsp;Lauren Palange,&nbsp;Caroline Astbury","doi":"10.1155/2019/4361630","DOIUrl":"https://doi.org/10.1155/2019/4361630","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1155/2019/5384295.].</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2019/4361630","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37487003","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Two Novel Variants in the ATRX Gene Associated with Variable Phenotypes","authors":"D. Hettiarachchi, B. A. P. S. Pathirana, P. Kumarasiri, V. Dissanayake","doi":"10.1155/2019/2687595","DOIUrl":"https://doi.org/10.1155/2019/2687595","url":null,"abstract":"The X-linked alpha-thalassemia mental retardation (ATR-X) syndrome is a rare genetic condition caused by mutations in the X‐encoded gene ATRX. Here we describe two unrelated patients of Sri Lankan origin with novel missense variants in the ATRX gene: c.839C>T|p.Cys280Tyr and c.5369C>T|p.Ala1790Val. These two novel variants were associated with variable phenotypes which clinically resembled X-linked mental retardation-hypotonic facies syndrome and Smith-Fineman-Myers syndrome respectively. These cases expand the clinical spectrum of ATR-X syndrome and open new opportunities for the molecular diagnosis of ATRX mutations in male patients with severe global developmental delay and intellectual disabilities.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2019-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"87162087","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}