scholarly journals A SMARCA2 Mutation in the First Case Report of Nicolaides-Baraitser Syndrome in Latin America: Genotype-Phenotype Correlation

2017 ◽  
Vol 2017 ◽  
pp. 1-4 ◽  
Author(s):  
Ana Isabel Sánchez ◽  
Jorge Armando Rojas
Keyword(s):  
Latin America ◽  
Case Report ◽  
Language Impairment ◽  
De Novo ◽  
Signs And Symptoms ◽  
Facial Features ◽  
Missense Mutations ◽  
De Novo Mutations ◽  
Lower Lip ◽  
First Case

Nicolaides-Baraitser syndrome (NCBRS) is a rare and well-recognized entity that was first described in 1993, with a prevalence that is currently not known. It is recognized as a distinctive entity, with some variability in its signs and symptoms. The most important characteristics include intellectual disability, peculiar facial features including sparse scalp hair, coarse facial features, low frontal hairline, and microcephaly, and seizures. Additional features may include epicanthic folds, thin upper lip vermilion with thick lower lip vermilion, skeletal abnormalities, and severe language impairment. The disorder is inherited in an autosomal dominant manner caused by de novo mutations in the SMARCA2 gene, with most being missense mutations. We report a young adult patient with NCBRS and, to our knowledge, the first case report of the syndrome in Latin America with a confirmed molecular diagnosis and a mild-to-moderate phenotype.

WDR45 Gene and Its Role in Pediatric Epilepsies

2021 ◽  
Author(s):  
Federica Filosco ◽  
Sebastiano Billone ◽  
Ausilia Collotta ◽  
Tiziana Timpanaro ◽  
Monica Tosto ◽  
...  
Keyword(s):  
Language Impairment ◽  
Pediatric Patients ◽  
De Novo ◽  
Somatic Mosaicism ◽  
Brain Magnetic Resonance Imaging ◽  
Iron Accumulation ◽  
Psychomotor Development ◽  
Specific Gene ◽  
Brain Iron ◽  
De Novo Mutations

AbstractWD repeat domain 45 (WDR45) gene has been increasingly found in patients with developmental delay (DD) and epilepsy. Previously, WDR45 de novo mutations were reported in sporadic adult and pediatric patients presenting iron accumulation, while heterozygous mutations were associated with β-propeller protein-associated neurodegeneration (BPAN), a subtype of neurodegeneration with brain iron accumulation disorders, characterized by extrapyramidal movement disorders and abnormal accumulation of iron in the basal ganglia. Overall, people harboring WDR45 mutations have moderate to severe DD and different types of seizures. The phenotype of adult patients is characterized by extrapyramidal movement, dystonia, parkinsonism, language impairment, and involvement of the substantia nigra and in the globus pallidus at brain magnetic resonance imaging. Importantly, there are no findings of brain iron accumulation in brain in BPAN patients in the first decade of life, thus suggesting a progressive course of the disease. Comparatively, the main phenotype of pediatric patients is epilepsy with early onset, most of which present infantile spasms and arrest or regression of psychomotor development. The phenotype of patients with WDR45 mutations is variable, being different if caused by somatic mosaicism or germline mutations, and presenting with a different spectrum of manifestations in males and females. The treatment of affected individuals is symptomatic. Regarding the seizures, specific, gene-based approaches with specific antiepileptic drugs are not currently available. The early diagnosis of BPAN could be useful in some aspects, such as providing families a supportive treatment to their affected children.

scholarly journals MED13L-related intellectual disability due to paternal germinal mosaicism

2021 ◽  
pp. mcs.a006124
Author(s):  
Beata Bessenyei ◽  
Istvan Balogh ◽  
Attila Mokanszki ◽  
Aniko Ujfalusi ◽  
Rolph Pfundt ◽  
...  
Keyword(s):  
Intellectual Disability ◽  
De Novo ◽  
Mediator Complex ◽  
Facial Dysmorphism ◽  
Facial Features ◽  
Speech Delay ◽  
Motor Delay ◽  
First Case ◽  
Intragenic Deletion ◽  
Germinal Mosaicism

The MED13L-related intellectual disability or MRFACD syndrome (Mental retardation and distinctive facial features with or without cardiac defects; MIM # 616789) is one of the most common form of syndromic intellectual disability with about a hundred cases reported so far. Affected individuals share overlapping features comprising intellectual disability, hypotonia, motor delay, remarkable speech delay, and a recognizable facial gestalt. De novo disruption of the MED13L gene by deletions, duplications or sequence variants has been identified deleterious. Siblings affected by intragenic deletion transmitted from a mosaic parent have been reported once in the literature. We now present the first case of paternal germinal mosaicism for a missense MED13L variant causing MRFACD syndrome in one of the father's children and be the likely cause of intellectual disability and facial dysmorphism in the other. As part of the Mediator complex, the MED proteins have an essential role in regulating transcription. 32 subunits of the Mediator complex genes have been linked to congenital malformations that are now acknowledged as transcriptomopathies. The MRFACD syndrome has been suggested to represent a recognizable phenotype.

Drug Rash With Eosinophilia and Systemic Symptoms (DRESS) Syndrome Probably Related to Cefpodoxime: A Case Report

2019 ◽  
pp. 089719001986609 ◽  
Author(s):  
Tirin Babu ◽  
George Mathew Panachiyil ◽  
Juny Sebastian ◽  
Veeranna Shastry
Keyword(s):  
Case Report ◽  
Signs And Symptoms ◽  
Side Effect Profile ◽  
Drug Reactions ◽  
Dress Syndrome ◽  
First Case ◽  
Drug History ◽  
Drug Rash ◽  
Systemic Symptoms ◽  
Favorable Side Effect Profile

Cefpodoxime is a common antibiotic with a favorable side effect profile. Drug Rash with Eosinophilia and Systemic Symptoms (DRESS) syndrome has been described with several cephalosporins but not cefpodoxime. We report the probable first case of cefpodoxime-induced DRESS syndrome in a 52-year-old female patient. In our case, the patient presented with symptoms of DRESS syndrome 16 days after initiation of cefpodoxime. This case highlights the necessity of consideration of an iatrogenic reason for presenting signs and symptoms at all times. Reinforcing the importance of taking a thorough drug history and considering drug reactions even if onset of symptoms are delayed.

scholarly journals Leukoencephalopathia, demyelinating peripheral neuropathy and dural ectasia explained by a not formerly described de novo mutation in the SAMD9L gene, ends 27 years of investigations – A case report

2019 ◽  
Author(s):  
Sofia Thunström ◽  
Markus Axelsson
Keyword(s):  
Case Report ◽  
Peripheral Neuropathy ◽  
De Novo ◽  
Age Of Onset ◽  
De Novo Mutation ◽  
Missense Mutations ◽  
Dural Ectasia ◽  
Whole Exome ◽  
Demyelinating Peripheral Neuropathy ◽  
Multiple Cysts

Abstract Background: Missense mutations in SAMD9L gene is associated with ataxia-pancytopenia syndrome (ATXPC), OMIM#159550. Common clinical features in these patients include neurological and hematological symptoms. The phenotype and age of onset is variable. Case Presentation: In this case report whole exome sequencing (WES) revealed a not previously reported de novo variant c.2686T>G, p.(Phe896Val) in SAMD9L in a patient with widespread findings of slow developing pathology in the peripheral and central nervous system. The clinical picture was dominated by neurological symptoms, unlike previously described cases, and in addition dural ectasias and multiple cysts in the brain was observed using magnetic resonance imaging. Conclusions: This case underscores the effect of variable expressivity, i.e. different mutations in the same gene can cause different phenotypes. Keywords: Leukoencephalopathia, demyelinating peripheral neuropathy, dural ectasia explained, de novo mutation, the SAMD9L gene.

scholarly journals A de novo paradigm for male infertility

2021 ◽  
Author(s):  
MS Oud ◽  
RM Smits ◽  
HE Smith ◽  
FK Mastrorosa ◽  
GS Holt ◽  
...  
Keyword(s):  
Male Infertility ◽  
De Novo ◽  
P Value ◽  
Missense Mutations ◽  
Loss Of Function ◽  
De Novo Mutations ◽  
Systematic Analysis ◽  
Significant Enrichment

IntroductionDe novo mutations (DNMs) are known to play a prominent role in sporadic disorders with reduced fitness1. We hypothesize that DNMs play an important role in male infertility and explain a significant fraction of the genetic causes of this understudied disorder. To test this hypothesis, we performed trio-based exome-sequencing in a unique cohort of 185 infertile males and their unaffected parents. Following a systematic analysis, 29 of 145 rare protein altering DNMs were classified as possibly causative of the male infertility phenotype. We observed a significant enrichment of Loss-of-Function (LoF) DNMs in LoF-intolerant genes (p-value=1.00×10-5) as well as predicted pathogenic missense DNMs in missense-intolerant genes (p-value=5.01×10-4). One DNM gene identified, RBM5, is an essential regulator of male germ cell pre-mRNA splicing2. In a follow-up study, 5 rare pathogenic missense mutations affecting this gene were observed in a cohort of 2,279 infertile patients, with no such mutations found in a cohort of 5,784 fertile men (p-value=0.009). Our results provide the first evidence for the role of DNMs in severe male infertility and point to many new candidate genes affecting fertility.

scholarly journals A First-Case Report of Pycnodysostosis in an Omani Boy

2020 ◽  
Author(s):  
Musallam Al-Araimi ◽  
Aliya Al-Hosni ◽  
Ashwaq Al Maimani
Keyword(s):  
Case Report ◽  
Short Stature ◽  
Sanger Sequencing ◽  
Deoxyribonucleic Acid ◽  
Cathepsin K ◽  
Facial Features ◽  
The Novel ◽  
First Case ◽  
Bone Disorder ◽  
Exome Sequence

AbstractHere we report on the genetic findings of a 9-year-old Omani boy with a rare inherited bone disorder. The patient's clinical features include dysmorphic facial features, short stature, and skeletal abnormalities. Exome sequence of the patient's deoxyribonucleic acid revealed a variant in the cathepsin K gene, which was confirmed by Sanger sequencing. These findings established the diagnosis of pycnodysostosis (PKND). To the best of the authors' knowledge, this case is the first case to be reported in the Gulf Cooperative Region of the novel PKND with molecular confirmation.

scholarly journals Pre- and Post-Zygotic TP53 De Novo Mutations in SHH-Medulloblastoma

Cancers ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2503
Author(s):  
Jacopo Azzollini ◽  
Elisabetta Schiavello ◽  
Francesca Romana Buttarelli ◽  
Carlo Alfredo Clerici ◽  
Laura Tizzoni ◽  
...  
Keyword(s):  
Family History ◽  
De Novo ◽  
Wide Spectrum ◽  
De Novo Mutations ◽  
Autosomal Dominant Disorder ◽  
P53 Overexpression ◽  
Tp53 Mutations ◽  
Li Fraumeni Syndrome ◽  
First Case ◽  
Germline Testing

Li-Fraumeni syndrome (LFS) is an autosomal dominant disorder caused by mutations in the TP53 gene, predisposing to a wide spectrum of early-onset cancers, including brain tumors. In medulloblastoma patients, the role of TP53 has been extensively investigated, though the prevalence of de novo mutations has not been addressed. We characterized TP53 mutations in a monocentric cohort of consecutive Sonic Hedgehog (SHH)-activated medulloblastoma patients. Germline testing was offered based on tumor p53 immunostaining positivity. Among 24 patients, three (12.5%) showed tumor p53 overexpression, of whom two consented to undergo germline testing and resulted as carriers of TP53 mutations. In the first case, family history was uneventful and the mutation was not found in either of the parents. The second patient, with a family history suggestive of LFS, unexpectedly resulted as a carrier of the mosaic mutation c.742=/C>T p.(Arg248=/Trp). The allele frequency was 26% in normal tissues and 42–77% in tumor specimens. Loss of heterozygosity (LOH) in the tumor was also confirmed. Notably, the mosaic case has been in complete remission for more than one year, while the first patient, as most TP53-mutated medulloblastoma cases from other cohorts, showed a severe and rapidly progressive disease. Our study reported the first TP53 mosaic mutation in medulloblastoma patients and confirmed the importance of germline testing in p53 overexpressed SHH-medulloblastoma, regardless of family history.

scholarly journals Complete Midline Cleft of Lower Lip, Mandible, Tongue, Floor of Mouth with Neck Contracture: A Case Report and Review of Literature

2015 ◽  
Vol 8 (4) ◽  
pp. 363-369 ◽  
Author(s):  
Anantheswar Y. N. Rao
Keyword(s):  
Case Report ◽  
World Literature ◽  
Rare Condition ◽  
Female Child ◽  
Flexion Contracture ◽  
Lower Lip ◽  
Floor Of The Mouth ◽  
First Case ◽  
Manubrium Sterni ◽  
Midline Cleft

Midline cleft of the lower lip and mandible is an extremely rare condition. Since 1819, when the first case was reported by Couronne, fewer than 80 cases have been described in the world literature so far. The cleft has also been described as facial cleft no. 30 by Paul Tessier. The condition varies in severity from a mild variety in which there is a submucous cleft and notching in the lower lip to a severe variety, involving the tongue, floor of the mouth, mandible, absent hyoid, atrophic neck muscles, and sternum. In this case report, a female child having complete midline cleft of the lower lip and mandible, with bifid tongue stuck to the floor of the mouth, absent hyoid bone and flexion contracture band extending from the confluence of the tip of the tongue, floor of the mouth, cleft mandible to the manubrium sterni is described, with special emphasis on surgical planning and management.

scholarly journals Clinical and Molecular Spectrum of Glutamate Dehydrogenase Gene Defects in 26 Chinese Congenital Hyperinsulinemia Patients

2018 ◽  
Vol 2018 ◽  
pp. 1-6 ◽  
Author(s):  
Chang Su ◽  
Xue-Jun Liang ◽  
Wen-Jing Li ◽  
Di Wu ◽  
Min Liu ◽  
...  
Keyword(s):  
Glutamate Dehydrogenase ◽  
De Novo ◽  
Mutational Analysis ◽  
Age At Onset ◽  
Normal Serum ◽  
Protein Restriction ◽  
Chinese Patients ◽  
Congenital Hyperinsulinism ◽  
Missense Mutations ◽  
De Novo Mutations

Objective. To characterize the genotype and phenotype of Chinese patients with congenital hyperinsulinism (CHI) caused by activating mutations in GLUD1, the gene that encodes mitochondrial enzyme glutamate dehydrogenase (GDH). Methods. The clinical data of glutamate dehydrogenase hyperinsulinism (GDH-HI) patients were reviewed, and gene mutations were confirmed by whole exome sequencing (WES) and Sanger DNA sequencing. Results. Twenty-six patients with GDH-HI heterozygous missense mutations were identified from 240 patients diagnosed as congenital hyperinsulinism over past 15 years. The median age at onset was 8 months (range: 1 day of life to 3 years). Seizure disorder was common in our cohort of patients (23/26). Four patients had normal serum ammonia levels; the median serum concentration was 101 μmol/L (range: 37–190 μmol/L). Hypoglycemic symptoms could be triggered by fasting or protein meals in all patients while blood glucose could be well controlled in all patients with diazoxide. Dosage of diazoxide could be reduced by protein restriction. Attempts to lower ammonia levels failed with different therapies such as protein restriction, benzoate, or N-carbamoyl glutamate. In follow-up, 15 of 26 patients had normal intelligence. Eleven patients developed epilepsy at the age of 6 months to 11 years. De novo mutations in GLUD1 were found in 24 cases, and dominant inheritance was observed in the other two; all were heterozygous. A total of 35% (9/26) patients carried c.1493C>T (p.S445L) mutation. Conclusions. Phenotypic heterogeneity of GDH-HI patients was observed within the Chinese cohort in the present study. The fact that most patients had a GLUD1 p. S445L mutation implies that this site could be a hotspot in Chinese patients. A high frequency of GDH-HI with normal ammonia has been reported in this study. Hence, GLUD1 mutational analysis may be an important method to differential diagnosis of GDH-HI from other diazoxide-responsive CHI in Chinese patients.

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