Case Reports in Genetics最新文献

{"title":"A Neonatal Patient Diagnosed with a <i>COL4A1</i> Mutation Presenting with Hemorrhagic Infarction and Severe Jaundice.","authors":"Akihiro Kirimura,&nbsp;Hajime Yasuhara,&nbsp;Soshi Hachisuka,&nbsp;Kumiko Takagi,&nbsp;Reiko Ebisu,&nbsp;Ayako Ohgitani,&nbsp;Hideki Minowa","doi":"10.1155/2022/1594364","DOIUrl":"https://doi.org/10.1155/2022/1594364","url":null,"abstract":"<p><p>We report a patient diagnosed with a <i>COL4A1</i> mutation in the early postnatal period. Patients with early postnatal jaundice, intracranial lesions that are negative for TORCH syndrome, and recurrent hemolytic anemia should be suspected of having a <i>COL4A1/COL4A2</i> gene mutation.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-10-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9586792/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40665258","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":"Homozygous Autosomal Recessive <i>DIAPH1</i> Mutation Associated with Central Nervous System Involvement and Aspergillosis: A Rare Case.","authors":"Hossein Esmaeilzadeh,&nbsp;Rafat Noeiaghdam,&nbsp;Leila Johari,&nbsp;Seyed Ali Hosseini,&nbsp;Sayyed Hesamedin Nabavizadeh,&nbsp;Soheila Sadat Alyasin","doi":"10.1155/2022/4142214","DOIUrl":"https://doi.org/10.1155/2022/4142214","url":null,"abstract":"<p><p>The <i>DIAPH1</i> gene fulfills critical immune and neurodevelopmental roles. It encodes the mammalian Diaphanous-related formin (mDia1) protein, which acts downstream of Rho GTPases to promote F-actin polymerization and stabilize microtubules. During mitosis, this protein is expressed in human neuronal precursor cells and considerably affects spindle formation and cell division. In humans, dominant gain-of-function <i>DIAPH1</i> variants cause sensorineural deafness and macrothrombocytopenia (DFNA1), while homozygous <i>DIAPH1</i> loss leads to seizures, cortical blindness, and microcephaly syndrome (SCBMS). To date, only 16 patients with SCBMS have been reported, none of whom were from Iran. Furthermore, aspergillosis is yet to be reported in patients with homozygous <i>DIAPH1</i> loss, and the link between SCBMS and immunodeficiency remains elusive. In this study, we shed further light on this matter by reporting the clinical, genetic, and phenotypic characteristics of an Iranian boy with a long history of recurrent infections, diagnosed with SCBMS and immunodeficiency (NM_005219.5 c.3145C > <i>T</i>; p.R1049X variant) following aspergillosis and SARS-CoV-2 coinfection.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537009/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33496369","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":"BAP1 Tumour Predisposition Syndrome Due to Whole BAP1 Gene Deletion.","authors":"Dinusha Pandithan,&nbsp;Sonja Klebe,&nbsp;Grace McKavanagh,&nbsp;Lesley Rawlings,&nbsp;Sui Yu,&nbsp;Jillian Nicholl,&nbsp;Nicola Poplawski","doi":"10.1155/2022/5503505","DOIUrl":"https://doi.org/10.1155/2022/5503505","url":null,"abstract":"<p><p>BRCA-1-associated protein-1 (BAP1) tumour predisposition syndrome (BAP1-TPDS) is a dominant hereditary cancer syndrome. The full spectrum of associated malignancies is yet to be fully characterised. We detail the phenotypic features of the first reported family with a whole BAP1 gene deletion. This report also adds to the emerging evidence that the rhabdoid subtype of meningioma is a part of the clinical spectrum of this tumour predisposition syndrome.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9489403/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33478473","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":"An Atypical Presentation of Pyridoxine-Dependent Epilepsy Diagnosed with Whole Exome Sequencing and Treated with Lysine Restriction and Supplementation with Arginine and Pyridoxine.","authors":"Jiyoung Kim,&nbsp;Angela Pipitone Dempsey,&nbsp;Sun Young Kim,&nbsp;Meral Gunay-Aygun,&nbsp;Hilary J Vernon","doi":"10.1155/2022/7138435","DOIUrl":"https://doi.org/10.1155/2022/7138435","url":null,"abstract":"<p><p>Pyridoxine dependent-developmental and epileptic encephalopathy (PD-DEE) or pyridoxine-dependent epilepsy (PDE) is a rare autosomal recessive disorder caused by biallelic pathogenic variants in ALDH7A1. It classically presents as intractable infantile-onset seizures unresponsive to multiple antiepileptic drugs (AEDs) but with a profound response to large doses of pyridoxine (B6). We report a case of PDE with an atypical clinical presentation. The patient presented at 3 days of life with multifocal seizures, fever, increased work of breathing, decreased left ventricular systolic function, and lactic acidosis, raising suspicion for a mitochondrial disorder or infectious process. Within 1.5 weeks of presentation, seizure activity resolved with antiepileptic therapy. Whole exome sequencing (WES) revealed homozygous pathogenic variants in ALDH7A1 (c.1279G > <i>C</i>, p.E427Q) and confirmed the diagnosis of PDE. Follow-up biochemical testing demonstrated elevated urine pipecolic acid. In the second week of life, the patient was initiated on triple therapy, including pyridoxine supplementation, low lysine diet, and arginine supplementation, which he tolerated well. Urine pipecolic acid levels responded accordingly after initiation of therapy. Our case illustrates the diagnostic challenges in PDE, the utility of rapid WES in such cases, and the response in urine pipecolic acid to therapy.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9448604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33455502","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":"Rapid Progression of Heterotopic Ossification in Severe Variant of Fibrodysplasia Ossificans Progressiva with p.Arg258Gly in ACVR1: A Case Report and Review of Clinical Phenotypes.","authors":"Kosei Hasegawa,&nbsp;Hiroyuki Tanaka,&nbsp;Natsuko Futagawa,&nbsp;Hiroyuki Miyahara,&nbsp;Hirokazu Tsukahara","doi":"10.1155/2022/5021758","DOIUrl":"https://doi.org/10.1155/2022/5021758","url":null,"abstract":"<p><p>Fibrodysplasia ossificans progressiva (FOP) is a rare skeletal disorder characterized by congenital malformation of the great toes and progressive heterotopic ossification. Malformation of the great toes appears at birth, while heterotopic ossification generally occurs during childhood and rarely occurs during infancy. Classical FOP results from the heterozygous p.Arg206His variant of the ACVR1 gene, which encodes Activin A receptor type 1. Recently, some atypical FOP patients with other ACVR1 gene variants and clinical features that are not observed in classical FOP patients have been reported. Herein, we describe a girl with severe FOP and multiple anomalies, including syndactyly of the hands and feet, nail agenesis, mandibular hypoplasia, heterotopic ossification occurring from infancy, and congenital cardiac malformation. In our patient, we identified de novo occurrence of the heterozygous p.Arg258Gly variant of ACVR1, which has previously been reported in only two severe FOP patients. Heterotopic ossification occurred earlier and more frequently compared with classical FOP patients. We present the time-series changes in heterotopic ossification in our patient and compare her clinical features with those of the previously reported patients with p.Arg258Gly. Our report deepens understanding of the clinical features in severe FOP with p.Arg258Gly and of FOP as a systemic disorder.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9436604/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40349771","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":"Novel Homozygous TTI2 Variant Causing Autosomal Recessive Syndromic Intellectual Disability and Primary Microcephaly from Pakistan: A Case Report (Exome Report).","authors":"Zul Qarnain,&nbsp;Fatima Khan,&nbsp;Fizza Akbar,&nbsp;Salman Kirmani","doi":"10.1155/2022/2766957","DOIUrl":"https://doi.org/10.1155/2022/2766957","url":null,"abstract":"<p><p>We describe a male patient with a novel TTI2 variant, which has not been previously associated with a human phenotype. His features include intellectual disability, primary microcephaly, delayed psychomotor development, speech delay, short stature, dysmorphic facial features, esotropia, kyphoscoliosis, and behavior abnormalities (Figure). Next generation sequencing revealed autosomal recessive TTI2 variant with uncertain significance, denoted as c.21_22insAAGCGCTCTG (p.Glu8Lysfs × 12). TTI2 encodes a regulator of DNA damage response and helps maintain steady levels of the PIKK family of protein kinases. No disease-causing variants in other genes potentially linked to his clinical presentation were identified. We report a novel loss-of-function homozygous variant in TTI2 that leads to syndromic intellectual disability and primary microcephaly.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9391182/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40628597","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":"Case Report of Fibro-Adipose Vascular Anomaly (FAVA) with Activating Somatic <i>PIK3CA</i> Mutation.","authors":"Jordan H Driskill,&nbsp;Helena Hwang,&nbsp;Alexandra K Callan,&nbsp;Dwight Oliver","doi":"10.1155/2022/9016497","DOIUrl":"https://doi.org/10.1155/2022/9016497","url":null,"abstract":"<p><p>Fibro-adipose vascular anomaly (FAVA) is a recently described complex and painful benign lesion found in young adults and the pediatric population composed of intramuscular vascular, fibrous, and adipose tissues. A previous report has identified the presence of somatic mosaic mutations in the gene for the catalytic subunit of phosphatidylinositol 3-kinase (<i>PIK3CA</i>) in cases of FAVA. Herein, we present a case of FAVA found in a 23-year-old male patient who presented with chronic wrist pain associated with a mass, and we identified an associated somatic activating mutation (H1047R) in <i>PIK3CA</i>. We briefly review the relevant literature surrounding the identification and histology of FAVA, the known mutational spectrum, downstream signaling pathways, and relevant treatment modalities. Our case highlights the association between FAVA and somatic mosaic activating <i>PIK3CA</i> mutations.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9363927/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40414989","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":"Novel <i>EPG5</i> Mutation Associated with Vici Syndrome Gene.","authors":"Frouzandeh Mahjoubi,&nbsp;Samira Shabani,&nbsp;Sogand Khakbazpour,&nbsp;Aylar Khaligh Akhlaghi","doi":"10.1155/2022/5452944","DOIUrl":"https://doi.org/10.1155/2022/5452944","url":null,"abstract":"<p><strong>Introduction: </strong>Vici syndrome (also known as immunodeficiency with cleft lip/palate, cataract, and hypopigmentation and absent corpus callosum) is considered as a progressive neurodevelopmental multisystem disorder. Till date, only 80 cases, including our patient, with this syndrome have been reported .This syndrome is characterized by agenesis of the corpus callosum, hypopigmentation of the eyes and hair, cataract, cardiomyopathy, combined immunodeficiency, hearing loss, seizures, and additional multisystem involvements which have been reported as case reports in the past. <i>Clinical Manifestation</i>. A 5-year-old girl, who is a product of consanguineous marriage, was referred to our center with developmental delay, optic atrophy, blindness, spasticity, seizure, movement disability, and spasticity. Her magnetic resonance imaging (MRI) test showed agenesis of the corpus callosum and her metabolic test reported normal.</p><p><strong>Materials and methods: </strong>In our laboratory, blood sample was obtained from the patient. DNA was extracted from lymphocytes, and whole exome sequencing (WES) using next generation Illumina sequencing was performed.</p><p><strong>Result: </strong>A novel (private), homozygous, nonsynonymous mutation c.A3206G (p.Y1069C Het) in <i>EPG5</i> gene was detected; in continuum, testing for this specific variant in her parents was carried out. DNA sequencing of the PCR-amplified product of the <i>EPG5</i> exon 17 showed that her parents were heterozygote for this variant. These mutations have not been reported before and therefore classified as variation of unknown significance (VUS). Mutation in this gene is shown to cause autosomal recessive Vici syndrome.</p><p><strong>Conclusion: </strong>Since clinical features of Vici syndrome has overlap, its diagnosis is differential and developmental delay occurs in 98% of reported cases. Vici syndrome can be considered as one of the main causes of developmental delay, and this syndrome can be introduced as a novel group of inherited neurometabolic conditions and congenital disorders.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9277209/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"40624405","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":"De Novo Heterozygous Mutation in FGFR2 Causing Type II Pfeiffer Syndrome.","authors":"Rafat Mosalli,&nbsp;Alfia Fatma,&nbsp;Mohammed A Almatrafi,&nbsp;Mayada Mazroua,&nbsp;Bosco Paes","doi":"10.1155/2022/4791082","DOIUrl":"https://doi.org/10.1155/2022/4791082","url":null,"abstract":"<p><p>Pfeiffer syndrome (PS) is an autosomal dominant disorder with three subtypes stemming from heterozygous mutations in the fibroblast growth factors FGFR1 and FGFR2. The subtypes overlap with heterogeneous clinical manifestations and variable prognosis dependent on neurological and respiratory compromise that impact short- and long-term outcomes and survival. We present a male, term infant with type II PS that was diagnostically suspected antenatally based on three-dimensional ultrasonographic findings that were confirmed postnatally by craniofacial tomography and magnetic resonance imaging. A new generation sequencing panel identified a unique <i>de novo</i> FGFR2, c.335 A > <i>G p</i>. Tyr112Cys variant, the first of its kind, and features that closely aligned with subtype II PS. Initial molecular results categorized the mutation as nonpathogenic, but it was later reclassified as pathogenic. Antenatal, multidisciplinary parental counseling about the tentative diagnosis and prognosis facilitated postnatal decisions that culminated in an informed choice for palliative care and early demise.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-06-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9537020/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"33496365","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":"Pitfalls in Genetic Testing for Consanguineous Pediatric Populations","authors":"M. Saleh, S. Colaiacovo, M. Napier, A. Prasad, C. Rupar, C. Prasad","doi":"10.1155/2022/9393042","DOIUrl":"https://doi.org/10.1155/2022/9393042","url":null,"abstract":"We describe the diagnostic odyssey of an eight-year-old female born to consanguineous parents. Our patient presented with global developmental delay, regression, microcephaly, spastic diplegia, and leukodystrophy confirmed on brain magnetic resonance imaging (MRI). She was found on whole exome sequencing (WES) to have dual genetic diagnoses. The first was a homozygous pathogenic HERC2 gene partial deletion of exons 43–45 that causes HERC2-related disorder. The second was a homozygous pathogenic variant (c.836 C > T, p.A279 V) in the SUMF1 gene responsible for multiple sulfatase deficiency. This case highlights some of the challenges in diagnosing consanguineous pediatric populations where standard genetic and metabolic testing may not provide answers. Our case further supports the recent American College of Medical Genetics and Genomics (ACMG) recommendation of WES as a first or second-tier test for patients with developmental delay, particularly in a population where the chances of dual diagnosis is high.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2022-05-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"75566678","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}