Case Reports in Genetics最新文献

{"title":"A Diagnosis of Maternal 22q Duplication and Mosaic Deletion following Prenatal Cell-Free DNA Screening.","authors":"Melissa A Hicks, Emilie Lalonde, Jessica Zoladz, Bernard Gonik, Salah Ebrahim","doi":"10.1155/2023/9127430","DOIUrl":"https://doi.org/10.1155/2023/9127430","url":null,"abstract":"<p><p>Concurrent microduplication and microdeletion of the chromosome 22q11.2 region are a rarely reported phenomenon. We describe a case of germline 22q11.21 microduplication syndrome with concurrent mosaic 22q11.2 deletion in a pregnant patient, identified by chromosomal microarray and FISH after noninvasive prenatal genetic screening (cfDNA) results discordant with family history. The patient was referred to maternal-fetal medicine (MFM) at 14 weeks' gestation secondary to an SNP-based cfDNA result of a suspected maternal 22q11.2 deletion and a fetal risk of 1 in 2 for 22q11.2 deletion syndrome. The patient reported a similar cfDNA result in a previous pregnancy; however postnatal chromosomal microarray on that child identified an atypical 22q11.21 microduplication. We report the maternal chromosomal microarray findings of a germline 726 kb 22q11.21 duplication and a mosaic 1.33 Mb 22q11.2 deletion and highlight the copy number variant data generated by cfDNA in this unique case. This family adds to the limited literature of concurrent 22q11.2 microduplication and microdeletion carriers.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"9127430"},"PeriodicalIF":0.0,"publicationDate":"2023-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10681772/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138463015","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 Rare 46,X,t(Y;10)(q12;p14) Balanced Translocation in Non-Obstructive Azoospermic Patient with Elevated FSH and LH Levels","authors":"Kousar Jahan Syeeda Khursheed, Mohammed Rahman Kaleemullah, Annu Joseph, Mohammed Hasan Al Durazi, Moiz Bakhiet","doi":"10.1155/2023/6722623","DOIUrl":"https://doi.org/10.1155/2023/6722623","url":null,"abstract":"Structural chromosomal aberrations like translocations have been shown to cause spermatogenic failure. We report a rare 46,X,t(Y;10)(q12;p14) balanced translocation in an otherwise healthy non-obstructive azoospermic male with high follicle-stimulating hormone (26.65 IU/L) and high luteinizing hormone (13.58 IU/L). The patient was referred to us after clinical, hormonal, and histopathological investigations to identify chromosomal abnormalities by karyotyping and fluorescence in situ hybridization (FISH). Analysis of the banding pattern by karyotyping followed by FISH confirmed reciprocal translocation and identified the breakpoints at Yq heterochromatin (Yq12) and 10p14. Further molecular tests including AZF microdeletion assay were done, and the results, which showed no mutations in the analyzed genes, were provided by the referring doctor. Thus, our study points to the importance of conventional cytogenetic techniques in the preliminary evaluation of a genetic abnormality in cases of infertility and would help the patient make an informed decision before pursuing assisted reproductive technology.","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"30 25","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-11-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"136281824","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":"Mosaicism in <i>BRPF1</i>-Related Neurodevelopmental Disorder: Report of Two Sisters and Literature Review.","authors":"Khaliunaa Bayanbold, Georgianne Younger, Benjamin Darbro, Alpa Sidhu","doi":"10.1155/2023/1692422","DOIUrl":"10.1155/2023/1692422","url":null,"abstract":"<p><p>Bromodomain and PHD finger containing 1 (<i>BRPF1</i>)-related neurodevelopmental disorder is characterized by intellectual disability, developmental delay, hypotonia, dysmorphic facial features, ptosis, and blepharophimosis. Both <i>de novo</i> and inherited pathogenic variants have been previously reported in association with this disorder. We report two affected female siblings with a novel variant in <i>BRPF1</i> c.2420_2433del (p.Q807Lfs<i>∗</i>27) identified through whole-exome sequencing. Their history of mild intellectual disability, speech delay, attention deficient hyperactivity disorder (ADHD), and ptosis align with the features previously reported in the literature. The absence of the <i>BRPF1</i> variant in parental buccal samples provides evidence of a <i>de novo</i> frameshift pathogenic variant, most likely as a result of parental gonadal mosaicism, which has not been previously reported. The frameshift pathogenic variant reported here lends further support to haploinsufficiency as the underlying mechanism of disease. We review the literature, compare the clinical features seen in our patients with others reported, and explore the possibility of genotype-phenotype correlation based on the location of pathogenic variants in <i>BRPF1</i>. Our study helps to summarize available knowledge and report the first case of a <i>de novo</i> frameshift pathogenic variant in <i>BRPF1</i> in two siblings with this neurodevelopmental disorder.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"1692422"},"PeriodicalIF":0.0,"publicationDate":"2023-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632058/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"72015630","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 Rare Case of Mosaic 3pter and 5pter Deletion-Duplication with Autism Spectrum Disorder and Dyskinesia.","authors":"Luna Bajracharya,&nbsp;Meena Lall,&nbsp;Sunita Bijarnia-Mahay,&nbsp;Praveen Kumar,&nbsp;Imran Mushtaq,&nbsp;Pushpa Saviour,&nbsp;Preeti Paliwal,&nbsp;Anju Joshi,&nbsp;Shruti Agarwal,&nbsp;Praveen Suman","doi":"10.1155/2023/7974886","DOIUrl":"10.1155/2023/7974886","url":null,"abstract":"<p><strong>Introduction: </strong>There is evidence that neurodevelopmental disorders are associated with chromosomal abnormalities. Current genetic testing can clinch an exact diagnosis in 20-25% of such cases. <i>Case Description.</i> A 3 years and 11 months old boy with global developmental delay had repetitive behaviors and hyperkinetic movements. He was stunted and underweight. He had ataxia, limb dyskinesia, triangular face, microcephaly, upward slanting palpebral fissure, hypertelorism, retrognathia, posteriorly rotated ears, long philtrum, thin lips, broad nasal tip, polydactyly, tappering fingers, and decreased tone in the upper and lower limbs with normal deep tendon reflexes. Magnetic resonance imaging of the brain, ultrasound of the abdomen, and ophthalmological evaluation were normal. Brain evoked response auditory revealed bilateral moderate hearing loss. He fulfilled the Diagnostic Statistical Manual 5 criteria for autism. In the Vineland Social Maturity Scale, his score indicated a severe delay in social functioning. His genetic evaluation included karyotyping, fluorescence in situ hybridization (FISH), and chromosomal microarray analysis (CMA). The karyotype report from high-resolution lymphocyte cultures was mos 46, XY, der(3)t(3; 5)(p26; p15.3)[50]/46, XY,der(5) t(3;5) (p26;p15.3)[50].ish. His karyotype report showed a very rare and abnormal mosaic pattern with two cell lines (50% each). Cell-line#1: 3pter deletion with 5pter duplication (3pter-/5pter+) and cell-line#2: 3pter duplication with 5pter deletion (3pter+/5pter-) derived from a <i>de novo</i> reciprocal translocation t(3; 5)(p26; p15.3) which was confirmed by FISH. The chromosomal microarray analysis report was normal. The two cell lines (50% each) seem to have balanced out at the whole genome level. Occupational, sensory integration, and behavior modification therapy were initiated for his autistic features, and anticholinergic trihexiphenidyl was prescribed for hyperkinetic movements.</p><p><strong>Conclusion: </strong>This case highlights a rare genetic finding and the need for timely genetic testing in a child with dysmorphism and autism with movement disorder to enable appropriate management and genetic counselling.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"7974886"},"PeriodicalIF":0.0,"publicationDate":"2023-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10593553/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"50158936","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":"Behavioral Phenotype, Electroclinical Features, and Treatment Options in Twins with <i>Lrp2</i> Candidate Variants (Donnay-Barrow/Foar Syndrome).","authors":"Alessia Mingarelli,&nbsp;Giovanni Battista Pipitone,&nbsp;Giacomo Torini,&nbsp;Maria Grazia Patricelli,&nbsp;Martina Totaro,&nbsp;Clara Colonna,&nbsp;Paola Carrera,&nbsp;Federico Raviglione","doi":"10.1155/2023/6679572","DOIUrl":"10.1155/2023/6679572","url":null,"abstract":"<p><p>The <i>LRP2</i> gene encodes megalin (LRP-2/GP330), a large single-spanning transmembrane glycoprotein that serves as a multiligand endocytotic receptor and mediates the reabsorption of albumin in the proximal renal tubule. <i>LRP2</i> is implicated in an autosomal recessive disorder characterized by dimorphisms, ocular anomalies, sensorineural deafness, proteinuria, epilepsy, and intellectual disability: a clinical condition called Donnai-Barrow syndrome (DBS) or facio-oculo-acoustico-renal (FOAR) syndrome. Pathogenic variants in <i>LRP2</i> have been reported in fewer than 60 patients, but a detailed description of seizures, electroencephalographic patterns, imaging findings, behavioral phenotype, and long-term follow-up is still needed. We provide a clinical report of two mono-chorionic twins with <i>LRP2</i>-related disease manifesting developmental delay, autistic features, seizures, proteinuria, and sleep disorders. By sequencing clinical exome, <i>LRP2</i> candidate rare variants, c.6815G > A, p. (Arg2272His), inherited from the mother and c.12725A > G, p. (Asp4242Gly), inherited from the father, were identified. During follow-up, at the age of 7, the main clinical features of the patients included insomnia, autistic features, severe psychomotor delay, and absent speech. The patients were under treatment with risperidone, antiseizure medications (ASMs), and supplementation of alpha-lactalbumin for self-injury and sleep disturbance. Our study confirmed the wide spectrum of behavioral and neurological and psychiatric features of this rare condition, suggesting new treatment options.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"6679572"},"PeriodicalIF":0.0,"publicationDate":"2023-09-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10560113/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41111207","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 15q11.2 Microdeletion Not Involving <i>SNORD116</i> Resulting in Prader-Willi Syndrome.","authors":"Molly M Crenshaw,&nbsp;Sharon L Graw,&nbsp;Dobromir Slavov,&nbsp;Theresa A Boyle,&nbsp;Daniel G Piqué,&nbsp;Matthew Taylor,&nbsp;Peter Baker","doi":"10.1155/2023/4225092","DOIUrl":"https://doi.org/10.1155/2023/4225092","url":null,"abstract":"<p><p>Loss of expression of paternally imprinted genes in the 15q11.2-q13 chromosomal region leads to the neurodevelopmental disorder Prader-Willi Syndrome (PWS). The PWS critical region contains four paternally expressed protein-coding genes along with small nucleolar RNA (snoRNA) genes under the control of the <i>SNURF-SNRPN</i> promoter, including the <i>SNORD116</i> snoRNA gene cluster that is implicated in the PWS disease etiology. A 5-7 Mb deletion, maternal uniparental disomy, or an imprinting defect of chromosome 15q affect multiple genes in the PWS critical region, causing PWS. However, the individual contributions of these genes to the PWS phenotype remain elusive. Reports of smaller, atypical deletions may refine the boundaries of the PWS critical region or suggest additional disease-causing mechanisms. We describe an adult female with a classic PWS phenotype due to a 78 kb microdeletion that includes only exons 2 and 3 of <i>SNURF-SNRPN</i> with apparently preserved expression of <i>SNORD116</i>.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"4225092"},"PeriodicalIF":0.0,"publicationDate":"2023-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10511293/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"41167931","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 Prenatal Presentation of CDK13-Related Disorder with a Novel Pathogenic Variant.","authors":"Michael Gibbs,&nbsp;Alysa Poulin,&nbsp;Yanwei Xi,&nbsp;Bita Hashemi","doi":"10.1155/2023/3437706","DOIUrl":"https://doi.org/10.1155/2023/3437706","url":null,"abstract":"<p><p>Cyclin-dependent kinase 13 (<i>CDK13</i>) is a member of the cyclin-dependent serine/threonine protein kinase family. Members of this family are well known for their essential roles as master switches in cell cycle control. CDK13-related disorder is a newly described genetic condition with characteristic clinical features including mild to severe intellectual disability, developmental delay, neonatal hypotonia, a variety of facial dysmorphism, behavioral problems, congenital heart defects, and structural brain abnormalities. We report a case of prenatal diagnosis of CDK13-related disorder. Detection of cystic hygroma with thickened nuchal fold led to prenatal genetic investigation, which identified a novel <i>de novo</i> likely pathogenic variant in the <i>CDK13</i> gene (c.900C > G, p.Tyr300^<i>∗</i>). Pregnancy was terminated and autopsy was performed. To our best knowledge, this is the first reported case of prenatal presentation of this condition with a detailed phenotypic description of the affected fetus.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"3437706"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10284631/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9710358","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":"Recurrent Ischemic Strokes due to Monogenic COL4A1 Mutation: The First Case Report from Latin America.","authors":"Emilio Israel Wong-Valenzuela,&nbsp;Daniel San Juan,&nbsp;José Santos Zambrano,&nbsp;Alejandra Camacho Molina,&nbsp;Miguel Angel Morales-Morales,&nbsp;Alejandro Lopez-Landa","doi":"10.1155/2023/6614837","DOIUrl":"https://doi.org/10.1155/2023/6614837","url":null,"abstract":"<p><p><i>Introduction</i>. Monogenic mutations as the cause of recurrent ischemic cerebral small-vessel disease with leukodystrophy are rare. COL4A1 gene mutations are a relatively new etiology of cerebrovascular lesions in young adults; however, any patient has been reported from Latin America. <i>Case Presentation</i>. We presented a Mexican young female with leukodystrophy and recurrent stroke secondary to COL4A1 monogenic mutation. <i>Discussion/Conclusion</i>. COL4A1 monogenic mutations are associated with cerebral small-vessel disease and other systemic manifestations. To date, there is little evidence to justify the treatment and prevention of recurrent strokes in patients with this mutation.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"6614837"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10482535/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10560262","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 TTN Mutation Causing Severe Congenital Myopathy and Uncertain Association with Infantile Hydrocephalus.","authors":"Palanikumar Balasundaram,&nbsp;Indirapriya Darshini Avulakunta,&nbsp;Leslie Delfiner,&nbsp;Paul Levy,&nbsp;Katie R Forman","doi":"10.1155/2023/5535083","DOIUrl":"https://doi.org/10.1155/2023/5535083","url":null,"abstract":"<p><p>Arthrogryposis multiplex congenita (AMC) is characterized by nonprogressive symmetric contractures of multiple joints with normal intellect and normal systemic examination. AMC is often due to fetal akinesia, which has neurologic, muscular, and connective tissue etiologies. We present a case of AMC due to a variant in the titin (TTN) gene in a term neonate. The infant is homozygous for this variant, <i>c.38442dup</i>, which is predicted to result in a truncated protein (<i>p.Pro12815Thr fs</i>∗<i>37, NM_001267550.2</i>). A literature search (PubMed) failed to find reports of this TTN variant. The variant was classified as pathogenic and submitted to ClinVar. Titin is the body's largest protein, expressed in skeletal and cardiac muscles and encoded by the TTN gene. Due to its large size (364 exons), the TTN gene has been difficult to sequence; the number of variants in the TTN gene and the spectrum of titinopathies are probably underestimated.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"5535083"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10368502/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9882290","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 Case of Congenital Hypotonia and Developmental Delay in an Individual with a <i>De Novo</i> Variant Outside of the Canonical HX-Motif of ATN1.","authors":"Elizaveta Makarova,&nbsp;Nicole R Legro,&nbsp;Ermal Aliu","doi":"10.1155/2023/1581876","DOIUrl":"https://doi.org/10.1155/2023/1581876","url":null,"abstract":"<p><p>We present a case of a 4-year-old female with a de novo heterozygous variant in the ATN1 gene. The whole exome sequencing was performed on the patient and her parents, and a likely pathogenic, de novo variant was identified in exon 5 of the ATN1 gene. There are two well-documented conditions associated with the ATN1 gene: congenital hypotonia, epilepsy, developmental delay, and digital anomalies (CHEDDA) syndrome and dentatorubral-pallidoluysian atrophy (DRPLA). Unlike DRPLA which is caused by an expanded trinucleotide repeat, CHEDDA syndrome is caused by variants in the histidine-rich (HX) motif at exon 7 of ATN1 similar to the de novo variant found in exon 5 of the presented individual. CHEDDA syndrome is a neurodevelopmental disorder previously documented in over 17 unrelated individuals. Compared to other documented CHEDDA syndrome cases, this individual shares similarities in respect to hypotonia, hearing impairment, impaired gross and fine motor ability, gastrointestinal abnormalities, hyperextensible joints, and frontal bossing. However, the individual presented here has only a moderate developmental delay and has acquired more developmental milestones such as higher-level language skills and more developed fine motor skills, than previously described individuals. The authors of this paper believe the patient's milder phenotype may be due to the variant's location outside of the canonic HX motif.</p>","PeriodicalId":30325,"journal":{"name":"Case Reports in Genetics","volume":"2023 ","pages":"1581876"},"PeriodicalIF":0.0,"publicationDate":"2023-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9845047/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10551742","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}