Case Reports in Genetics最新文献

{"title":"A Novel Mutation of <i>VPS</i>33<i>B</i> Gene Associated with Incomplete Arthrogryposis-Renal Dysfunction-Cholestasis Phenotype.","authors":"Eleni Agakidou,&nbsp;Charalampos Agakidis,&nbsp;Marios Kambouris,&nbsp;Nicoleta Printza,&nbsp;Maria Farini,&nbsp;Elina Vourda,&nbsp;Spyridon Gerou,&nbsp;Kosmas Sarafidis","doi":"10.1155/2020/8872294","DOIUrl":"https://doi.org/10.1155/2020/8872294","url":null,"abstract":"<p><p>Arthrogryposis-renal dysfunction-cholestasis (ARC) syndrome is an autosomal recessive disorder caused by mutations of the <i>VPS</i>33<i>B</i> encoding the vacuolar protein sorting 33B (VPS33B), which is involved in the intracellular protein sorting and vesicular trafficking. We report a rare case of ARC syndrome without arthrogryposis caused by a novel mutation of <i>VPS</i>33<i>B</i>. A female patient of Greek origin presented on the 14^th day of life with renal tubular acidosis, Fanconi syndrome, nephrogenic diabetes insipidus, and cholestasis with normal gamma-glutamyl transpeptidase, without arthrogryposis and dysmorphic features. She was born to apparently healthy, nonconsanguineous parents. Additional features included dry and scaling skin, generalized hypotonia, hypoplastic corpus callosum, neurodevelopmental delay, failure to thrive, short stature, recurrent febrile episodes with and without infections, and gastrointestinal bleeding. DNA testing revealed that the patient was homozygous for the novel c.1098_1099delTG (p.Glu367Alafs<i>∗</i>17) mutation of exon 14 of <i>VPS</i>33<i>B</i> gene (NM_018668) on chromosome 15q26.1, leading to a nonsense frameshift variant of VPS33B with premature termination of translation. Her parents were heterozygous for the same <i>VPS</i>33<i>B</i> mutation. The prognosis was predictably poor in the context of the intractable polyuria necessitating long-term parenteral fluid administration via indwelling central catheter leading to catheter-related sepsis, to which she eventually succumbed at the age of 7 months. This is the first published <i>VPS</i>33<i>B</i> mutation in an ARC patient of Greek origin. The current case adds to the spectrum of ARC-associated <i>VPS</i>33<i>B</i> mutations and provides evidence supporting the existence of incomplete ARC phenotype. Increased awareness and early genetic testing for ARC are suggested in cases with isolated cholestasis and/or renal tubular dysfunction, even in the absence of arthrogryposis.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-09-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8872294","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38466687","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 Adolescent with a Rare <i>De Novo</i> Distal Trisomy 6p and Distal Monosomy 6q Chromosomal Combination.","authors":"Leia A Peterman,&nbsp;Gail H Vance,&nbsp;Erin E Conboy,&nbsp;Katelynn Anderson,&nbsp;David D Weaver","doi":"10.1155/2020/8857628","DOIUrl":"https://doi.org/10.1155/2020/8857628","url":null,"abstract":"<p><p>We report on a 12-year-old female with both a partial duplication and deletion involving chromosome 6. The duplication involves 6p25.3p24.3 (7.585 Mb) while the deletion includes 6q27q27 (6.244 Mb). This chromosomal abnormality is also described as distal trisomy 6p and distal monosomy 6q. The patient has a Chiari II malformation, hydrocephalus, agenesis of the corpus callosum, microcephaly, bilateral renal duplicated collecting system, scoliosis, and myelomeningocele associated with a neurogenic bladder and bladder reflux. Additional features have included seizures, feeding dysfunction, failure to thrive, sleep apnea, global developmental delay, intellectual disability, and absent speech. To our knowledge, our report is just the sixth case in the literature with concomitant distal 6p duplication and distal 6q deletion. Although a majority of chromosomal duplication-deletion cases have resulted from a parental pericentric inversion, the parents of our case have normal chromosomes. This is the first reported <i>de novo</i> case of distal 6p duplication and distal 6q deletion. Alternate explanations for the origin of the patient's chromosome abnormalities include parental gonadal mosaicism, nonallelic homologous recombination, or potentially intrachromosomal transposition of the telomeres of chromosome 6. Nonpaternity was considered but ruled out by whole exome sequencing analysis.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8857628","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38483721","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 Japanese Patient with Genitopatellar Syndrome Transiently Presenting with Cardiac Intramural Cavity during the Neonatal Period.","authors":"Kiichi Takahashi,&nbsp;Hiroyuki Adachi,&nbsp;Manatomo Toyono,&nbsp;Masato Ito,&nbsp;Akie Kato,&nbsp;Atsuko Noguchi,&nbsp;Tsutomu Takahashi","doi":"10.1155/2020/1731720","DOIUrl":"https://doi.org/10.1155/2020/1731720","url":null,"abstract":"<p><p>Genitopatellar syndrome (GPS) is a rare autosomal dominant disorder caused by de novo pathogenic variants in the <i>KAT6B</i> gene. It is characterized by genital abnormalities, patellar hypoplasia/agenesis, flexion contractures of the hips and knees, corpus callosum agenesis with microcephaly, and hydronephrosis and/or multiple renal cysts. More than half of patients with GPS have congenital heart defects, mostly atrial and/or ventricular septal defects, patent foramen ovale, and patent ductus arteriosus. We report a case of a Japanese neonate with a de novo heterozygous c.3769_3772delTCTA pathogenic variant in the <i>KAT6B</i> gene who presented with a cardiac intramural cavity of the ventricular septum at birth. The cavity unexpectedly disappeared at 1 month of age, but trabecular septal thinning and flash remained. The features of the cavity were not consistent with those of congenital ventricular diverticulum or aneurysm, and its identity and prognosis are still unclear. Because patients with GPS may exhibit various forms of cardiac malformation, careful cardiac examination and follow-up are required from birth in cases of suspected GPS.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/1731720","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38362135","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 Mutations in Pilomatrixoma, CTNNB1 p.s45F, and FGFR2 p.s252L: A Report of Three Cases Diagnosed by Fine-Needle Aspiration Biopsy, with Review of the Literature.","authors":"Cristina Aparecida Troques da Silveira Mitteldorf,&nbsp;Rafael Sarlo Vilela,&nbsp;Melissa Lissae Fugimori,&nbsp;Carla Daniele de Godoy,&nbsp;Renata de Almeida Coudry","doi":"10.1155/2020/8831006","DOIUrl":"https://doi.org/10.1155/2020/8831006","url":null,"abstract":"<p><p>Pilomatrixoma (<i>calcifying epithelioma of Malherbe</i>) is an uncommon benign skin appendageal tumor that differentiates toward hair matrix cells. It is misdiagnosed in up to 75% of cases by nondermatologists. Although the histopathological findings are well recognized and characteristic, diagnosis by fine-needle aspiration biopsy may be quite challenging. Several reports have emphasized the challenges in cytodiagnosis of pilomatrixoma, leading to a false-positive diagnosis. The lesions may show avidity for fludeoxyglucose on positron emission tomography/computed tomography scan, raising concern of a possible malignant neoplasm. CTNNB1 mutations have been reported in a high percentage of pilomatrixomas. Expression of <i>β</i>-catenin, the protein encoded by CTNNB1, is also frequently observed. To determine if routine cytological specimens can be successfully used to perform additional investigation and support or confirm the diagnosis in three cases of pilomatrixoma, we performed molecular analysis and immunohistochemistry to search for CTNNB1 mutation and <i>β</i>-catenin, respectively. <i>β</i>-Catenin positivity by immunohistochemistry was observed in basaloid cells in all three cases. Exon 3 mutations in <i>CTNNB1</i> were detected in all cases. In addition, we detected a fibroblast growth factor receptor 2 (FGFR2) mutation in one of the cases. We reviewed the literature and present the clinical and morphological characteristics that must be considered along with other findings to accurately achieve the correct diagnosis, in correlation with the results of the ancillary technique. In conclusion, routine cytological specimens can be successfully used to perform additional investigations and support cytodiagnosis in difficult cases.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8831006","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38362137","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 Novel <i>EMD</i> Mutation Identified by Whole-Exome Sequencing in Twins with Emery-Dreifuss Muscular Dystrophy.","authors":"Xiafei Dai,&nbsp;Rong Luo,&nbsp;Yang Chen,&nbsp;Chenqing Zheng,&nbsp;Yibin Tang,&nbsp;Hongmei Zhang,&nbsp;Ye Su,&nbsp;Tao He,&nbsp;Xiaoping Li","doi":"10.1155/2020/2071738","DOIUrl":"https://doi.org/10.1155/2020/2071738","url":null,"abstract":"<p><p>This case reports a novel hemizygous frameshift <i>EMD</i> mutation (c.487delA, p.Ser163fs) in twins of an Emery-Dreifuss muscular dystrophy family with severe cardiac involvement and mild muscle weakness. Their mother carried the same heterozygous mutation.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/2071738","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38362136","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":"Eye Manifestations of Shprintzen-Goldberg Craniosynostosis Syndrome: A Case Report and Systematic Review.","authors":"Jamie H Choi,&nbsp;Rachel Li,&nbsp;Rachel Gannaway,&nbsp;Tahnee N Causey,&nbsp;Anna Harrison,&nbsp;Natario L Couser","doi":"10.1155/2020/7353452","DOIUrl":"https://doi.org/10.1155/2020/7353452","url":null,"abstract":"<p><p>Shprintzen-Goldberg craniosynostosis syndrome (SGS) is a rare autosomal dominant condition that was first documented in literature in 1982. The disorder is caused by pathogenic variants in the proto-oncogene <i>SKI</i> gene, a known suppressor of TGF-<i>β</i> activity, located on chromosome 1p36. There is considerable phenotypic overlap with Marfan and Loeys-Dietz syndromes. Common clinical features of SGS include craniosynostosis, marfanoid habitus, hypotonia, dysmorphic facies, cardiovascular anomalies, and other skeletal and connective tissue abnormalities. Ocular manifestations may include hypertelorism, downslanting palpebral fissures, proptosis, myopia, and ectopia lentis. We describe a 25-year-old male with the syndrome. Genetic analysis revealed a novel c.350G>A (p.Arg117His) <i>de novo</i> variant, which was predicted to be pathogenic by the CTGT laboratory. The patient presented with dysmorphic features, marfanoid habitus, severe joint contractures, mitral valve insufficiency, aortic root dilatation, and a history of seizures. His ocular manifestations included hypertelorism, downslanting palpebral fissures, bilateral ptosis, and high myopia. Ophthalmic manifestations are an integral component of the syndrome; however, they have not been well characterized in the literature. From a systematic review of previously published cases to date, we summarize the eye and ocular adnexa manifestations reported.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/7353452","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"25401477","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":"\"Isolated\" Amelogenesis Imperfecta Associated with <i>DLX3</i> Mutation: A Clinical Case.","authors":"Anne-Laure Bonnet,&nbsp;Kevin Sceosole,&nbsp;Arabelle Vanderzwalm,&nbsp;Caroline Silve,&nbsp;Anne-Margaux Collignon,&nbsp;Celine Gaucher","doi":"10.1155/2020/8217919","DOIUrl":"https://doi.org/10.1155/2020/8217919","url":null,"abstract":"<p><p>Amelogenesis imperfecta (AI) represents rare tooth anomalies that affect the quality and/or quantity of the enamel. Clinical phenotypes display a wide spectrum, ranging from mild color changes to severe structural alterations with daily pain. However, all affect the quality of life because of mechanical, psychological, esthetic, and/or social repercussions. Several gene mutations have been linked to AI as a nonsyndromic (isolated) phenotype or a wider syndrome. This case report aimed to present a family with dental structure anomalies followed up in the dental department of the Louis Mourier Hospital (APHP, France) for their extremely poor dental condition. The proband and his mother were clinically diagnosed with AI, and genetic analysis revealed an already described variant in <i>DLX3</i>. Then, the family was further examined for tricho-dento-osseous syndrome. This report illustrates the challenge of diagnosing dental structure anomalies, specifically AI, in adults and highlights the need for an accurate and accessible molecular diagnosis for those anomalies to discriminate between isolated and syndromic pathologies.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8217919","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38295796","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":"Managing Sleep and Behavioral Problems in a Preschooler with <i>SATB2</i>-Associated Syndrome.","authors":"Nihit Kumar,&nbsp;Yuri A Zarate","doi":"10.1155/2020/8868458","DOIUrl":"https://doi.org/10.1155/2020/8868458","url":null,"abstract":"<p><p><i>SATB2</i>-associated syndrome is an autosomal dominant, multisystemic disorder with associated sleep and behavioral abnormalities. Evidence is limited on appropriate management strategies in this population. We describe the medical management of a four-year-old child with poor sleep and significant behavioral problems. After failing initial treatment with melatonin, we initiated treatment clonidine along with high doses of trazodone for sleep. Daytime treatment with quetiapine was added to successfully manage behavioral issues. We present the challenges associated with treatment strategies in children with this syndrome.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/8868458","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38249247","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":"Chromosome 20p Partial <i>De Novo</i> Duplication Identified in a Female Paediatric Patient with Characteristic Facial Dysmorphism and Behavioural Anomalies.","authors":"Shahzaib Khattak,&nbsp;Meryam Jan,&nbsp;Sara Warsi,&nbsp;Sohail Khattak","doi":"10.1155/2020/7093409","DOIUrl":"https://doi.org/10.1155/2020/7093409","url":null,"abstract":"<p><p>Copy number variations (CNVs) involving the <i>JAG1</i> gene are rare and infrequently reported in the scientific literature. Recently, a generally healthy young patient presenting with a history of behavioural concerns was referred to us. Herein, we discuss the patient, a 7-year-old female possessing a 0.797 Mb microduplication within the short arm of chromosome 20 at band 12.2. The patient generates considerable curiosity due to the rarity of her case, which includes a <i>de novo</i> partial duplication involving the <i>JAG1</i> gene. The patient exhibits a wide range of symptoms including facial dysmorphism (dolichocephaly, round face, tented philtrum, anteverted nares, and micrognathia), clinodactyly, and an inborn congenital heart defect. She presented with behavioural concerns including ADHD-I, SPD, motor clumsiness, and poor self-regulation. Deletions in <i>JAG1</i> are often linked to <i>Alagille Syndrome</i>; however, complete duplications have not been specifically identified as disease-causing. <i>JAG1</i> mutations are reported alongside various clinical features including facial dysmorphology, heart defects, vertebral abnormalities, and ocular dysmorphic features (strabismus, epicanthal folds, and slanted palpebral fissures). This particular microduplication is rare, and thus, limited data exist regarding its significance. To our knowledge, most reported duplications are larger than 0.797 Mb. This may define a critical region causing phenotypical changes in some patient cases.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-07-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/7093409","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"38220105","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":"Late Onset Ornithine Transcarbamylase Deficiency Triggered by an Acute Increase in Protein Intake: A Review of 10 Cases Reported in the Literature.","authors":"E Barkovich,&nbsp;A L Gropman","doi":"10.1155/2020/7024735","DOIUrl":"https://doi.org/10.1155/2020/7024735","url":null,"abstract":"<p><p>While the urea cycle disorders (UCDs) classically present in the neonatal stage, they have become increasingly recognized as a rare cause of unexplained hyperammonemic encephalopathy in adults. Many metabolic triggers for late-onset UCDs have been described in the literature including excessive protein intake. In this case series, ten such documented cases are reviewed with analysis of patient demographic, protein load, treatment course, and patient outcome. Common delays in treatment include recognition of hyperammonemia as the cause of encephalopathy and initiation of hemodialysis. In only one case was a diet history used to raise suspicion for a metabolic derangement. Metabolic disorders remain an important consideration in adults presenting with encephalopathy not explained by more common etiologies, and recent and remote dietary history may provide valuable information.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":null,"pages":null},"PeriodicalIF":0.0,"publicationDate":"2020-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://sci-hub-pdf.com/10.1155/2020/7024735","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"37904622","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}