Prenatal diagnosis of Bardet-Biedl syndrome: a multidisciplinary approach

2021 ◽  
Vol 14 (1) ◽  
pp. e238445
Author(s):  
Daniela Vila Real ◽  
Rosete Nogueira ◽  
Joaquim Sá ◽  
Cristina Godinho
Keyword(s):  
Prenatal Diagnosis ◽  
Family History ◽  
Genetic Disorder ◽  
Early Adulthood ◽  
Autosomal Recessive Inheritance ◽  
Bardet Biedl Syndrome ◽  
Incurable Disease ◽  
Whole Exome ◽  
History Of ◽  
Human Genetic Disorder

Bardet-Biedl syndrome (BBS) is a rare ciliopathic human genetic disorder with mainly an autosomal recessive inheritance. BBS phenotype develops over the years and diagnosis is usually made in late childhood or early adulthood. Prenatal diagnosis is rare in the absence of family history or consanguinity. We present a prenatal case without a family history of inherited diseases or consanguinity. Mid-trimester ultrasound revealed hyperechogenic kidneys and postaxial polydactyly putting us on track of BBS. The fetopathology supported this diagnosis and the whole-exome sequencing confirmed the hypothesis. Our case illustrates how high-resolution obstetric scan, detailed observation of fetal features and application of gene sequencing technology contribute to elucidate the aetiology of rare, yet disabling and incurable disease, with the particular setting of negative family history.

scholarly journals Hunting for Familial Parkinson’s Disease Mutations in the Post Genome Era

Genes ◽  
2021 ◽  
Vol 12 (3) ◽  
pp. 430
Author(s):  
Steven R. Bentley ◽  
Ilaria Guella ◽  
Holly E. Sherman ◽  
Hannah M. Neuendorf ◽  
Alex M. Sykes ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Family History ◽  
Rare Variants ◽  
Strong Family History ◽  
Disease Mutations ◽  
Whole Exome ◽  
History Of ◽  
Functional Consequences ◽  
Multiplex Families

Parkinson’s disease (PD) is typically sporadic; however, multi-incident families provide a powerful platform to discover novel genetic forms of disease. Their identification supports deciphering molecular processes leading to disease and may inform of new therapeutic targets. The LRRK2 p.G2019S mutation causes PD in 42.5–68% of carriers by the age of 80 years. We hypothesise similarly intermediately penetrant mutations may present in multi-incident families with a generally strong family history of disease. We have analysed six multiplex families for missense variants using whole exome sequencing to find 32 rare heterozygous mutations shared amongst affected members. Included in these mutations was the KCNJ15 p.R28C variant, identified in five affected members of the same family, two elderly unaffected members of the same family, and two unrelated PD cases. Additionally, the SIPA1L1 p.R236Q variant was identified in three related affected members and an unrelated familial case. While the evidence presented here is not sufficient to assign causality to these rare variants, it does provide novel candidates for hypothesis testing in other modestly sized families with a strong family history. Future analysis will include characterisation of functional consequences and assessment of carriers in other familial cases.

scholarly journals A Case Report of a Prenatally Missed Mowat-Wilson Syndrome With Isolated Corpus Callosum Agenesis

2021 ◽  
Vol 8 ◽  
pp. 2329048X2110065
Author(s):  
Nesrin Şenbil ◽  
Zeynep Arslan ◽  
Derya Beyza Sayın Kocakap ◽  
Yasemin Bilgili
Keyword(s):  
Corpus Callosum ◽  
Autosomal Dominant ◽  
Genetic Disorder ◽  
Gene Mutations ◽  
Hirschsprung Disease ◽  
Agenesis Of Corpus Callosum ◽  
Whole Exome ◽  
Congenital Cardiac Anomalies ◽  
History Of ◽  
Gene Mutation Analysis

Mowat–Wilson syndrome (MWS) is an autosomal dominant genetic disorder caused by ZEB2 gene mutations, manifesting with unique facial characteristics, moderate to severe intellectual problems, and congenital malformations as Hirschsprung disease, genital and ophthalmological anomalies, and congenital cardiac anomalies. Herein, a case of 1-year-old boy with isolated agenesis of corpus callosum (IACC) in the prenatal period is presented. He was admitted postnatally with Hirschsprung disease (HSCR), hypertelorism, uplifted earlobes, deeply set eyes, frontal bossing, oval-shaped nasal tip, ‘‘M’’ shaped upper lip, opened mouth and prominent chin, and developmental delay. Hence, MWS was primarily considered and confirmed by the ZEB2 gene mutation analysis. His karyotype was normal. He had a history of having a prenatally terminated brother with similar features. Antenatally detected IACC should prompt a detailed investigation including karyotype and microarray; even if they are normal then whole exome sequencing (WES) should be done.

Abstract 16468: Results of Research Genetic Testing in Pediatric Cardiomyopathy Patients Justify Broader Clinical Genetic Testing

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Stephanie M Ware ◽  
Steven E Lipshultz ◽  
Steven D Colan ◽  
Ling Shi ◽  
Charles E Canter ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Family History ◽  
Risk Stratification ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Clinical Genetic ◽  
Clinical Genetic Testing ◽  
Whole Exome ◽  
Pediatric Cardiomyopathy ◽  
History Of

Introduction: Pediatric cardiomyopathies are genetically heterogeneous diseases with high risk of death or cardiac transplant. Despite progress in identifying causes, the majority of cases remain idiopathic. Currrently, genetic testing is not performed in all children with cardiomyopathy. Gene identification leads to better individual risk stratification and has the potential to stimulate the development of therapies based on the underlying mutation. The aim of this study is to identify genetic mutations in pediatric cardiomyopathy patients using whole exome sequencing. Hypothesis: Sarcomeric mutations are under-diagnosed causes of all forms of cardiomyopathy in children. Methods: Probands with cardiomyopathy were recruited from 11 institutions. Results of clinical genetic testing prior to enrollment were collected. Whole exome sequencing was performed and mutations were identified in 35 genes currently available on clinical genetic testing panels. Results: The initial 154 probands subjected to exome included 78 patients with DCM, 43 with HCM, 14 with RCM, and 19 with LVNC, mixed, or unknown types. Familial disease was present in 38% and the remainder were idiopathic. Twenty-seven percent had positive clinical genetic testing prior to enrollment. Exome testing identified mutations in 38 subjects who had not had clinical testing, increasing the cohort positive testing rate to 55% (DCM, 34.6%; HCM, 74.4%; RCM, 71.4%). Forty-five percent of subjects with no family history of disease had an identifiable mutation. Conclusions: Pediatric cardiomyopathy patients have a high incidence of mutations that can be identified by clinically available genetic testing. Lack of a family history of cardiomyopathy was not predictive of normal genetic testing. These results support the broader use of genetic testing in pediatric patients with all functional phenotypes of cardiomyopathy to identify disease causation allowing better family risk stratification.

scholarly journals Case report: targeted whole exome sequencing enables the first prenatal diagnosis of the lethal skeletal dysplasia Osteocraniostenosis

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Lara Pemberton ◽  
Robert Barker ◽  
Anna Cockell ◽  
Vijaya Ramachandran ◽  
Andrea Haworth ◽  
...  
Keyword(s):  
Case Report ◽  
Prenatal Diagnosis ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Skeletal Dysplasia ◽  
Genetic Disorder ◽  
Specific Gene ◽  
Ultrasound Images ◽  
Whole Exome ◽  
Lethal Skeletal Dysplasia

Abstract Background Osteocraniostenosis (OCS) is a rare genetic disorder characterised by premature closure of cranial sutures, gracile bones and perinatal lethality. Previously, diagnosis has only been possible postnatally on clinical and radiological features. This study describes the first prenatal diagnosis of OCS. Case presentation In this case prenatal ultrasound images were suggestive of a serious but non-lethal skeletal dysplasia. Due to the uncertain prognosis the parents were offered Whole Exome Sequencing (WES), which identified a specific gene mutation in the FAMIIIa gene. This mutation had previously been detected in two cases and was lethal in both perinatally. This established the diagnosis, a clear prognosis and allowed informed parental choice regarding ongoing pregnancy management. Conclusions This case report supports the use of targeted WES prenatally to confirm the underlying cause and prognosis of sonographically suspected abnormalities.

Spontaneous intracranial hemorrhage and multiple intracranial aneurysms in a patient with Roberts/SC phocomelia syndrome

2011 ◽  
Vol 8 (5) ◽  
pp. 460-463 ◽  
Author(s):  
Anthony C. Wang ◽  
Joseph J. Gemmete ◽  
Catherine E. Keegan ◽  
Cordelie E. Witt ◽  
Karin M. Muraszko ◽  
...  
Keyword(s):  
Intracranial Aneurysms ◽  
Autosomal Recessive ◽  
Genetic Disorder ◽  
Autosomal Recessive Inheritance ◽  
Inheritance Pattern ◽  
Craniofacial Malformation ◽  
Ct Angiogram ◽  
Preoperative Ct ◽  
History Of ◽  
Spontaneous Intracranial Hemorrhage

Roberts/SC phocomelia syndrome (RBS) is a rare but distinct genetic disorder with an autosomal recessive inheritance pattern. It has been associated with microcephaly, craniofacial malformation, cavernous hemangioma, encephalocele, and hydrocephalus. There are no previously reported cases of RBS with intracranial aneurysms. The authors report on a patient with a history of RBS who presented with a spontaneous posterior fossa hemorrhage. Multiple small intracranial aneurysms were noted on a preoperative CT angiogram. The patient underwent emergency craniotomy for evacuation of the hemorrhage. A postoperative angiogram confirmed the presence of multiple, distal small intracranial aneurysms.

Relation of attachment style to family history of alcoholism and alcohol use disorders in early adulthood

2004 ◽  
Vol 75 (1) ◽  
pp. 47-53 ◽  
Author(s):  
Martha Vungkhanching ◽  
Kenneth J Sher ◽  
Kristina M Jackson ◽  
Gilbert R Parra
Keyword(s):  
Family History ◽  
Alcohol Use ◽  
Attachment Style ◽  
Early Adulthood ◽  
Alcohol Use Disorders ◽  
History Of

scholarly journals Clinical implications of identifying pathogenic variants in aortic dissection patients with whole exome sequencing

2018 ◽  
Author(s):  
Brooke N. Wolford ◽  
Whitney E. Hornsby
Keyword(s):  
Family History ◽  
Aortic Dissection ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Family Members ◽  
Aortic Disease ◽  
Thoracic Aortic Dissection ◽  
Pathogenic Variants ◽  
Whole Exome ◽  
History Of

ABSTRACTBackgroundThoracic aortic dissection is an emergent life-threatening condition. Routine screening for genetic variants causing thoracic aortic dissection is not currently performed for patients or their family members.MethodsWe performed whole exome sequencing of 240 patients with thoracic aortic dissection (n=235) or rupture (n=5) and 258 controls matched for age, sex, and ancestry. Blinded to case-control status, we annotated variants in 11 genes for pathogenicity.ResultsTwenty-four pathogenic variants in 6 genes (COL3A1, FBN1, LOX, PRKG1, SMAD3, TGFBR2) were identified in 26 individuals, representing 10.8% of aortic cases and 0% of controls. Among dissection cases, we compared those with pathogenic variants to those without and found that pathogenic variant carriers had significantly earlier onset of dissection (41 vs. 57 years), higher rates of root aneurysm (54% vs. 30%), less hypertension (15% vs. 57%), lower rates of smoking (19% vs. 45%), and greater incidence of aortic disease in family members. Multivariable logistic regression showed significant risk factors associated with pathogenic variants are age <50 [odds ratio (OR) = 5.5; 95% CI: 1.6-19.7], no history of hypertension (OR=5.6; 95% CI: 1.4-22.3) and family history of aortic disease (mother: OR=5.7; 95% CI: 1.4-22.3, siblings: OR=5.1; 95% CI 1.1-23.9, children: OR=6.0; 95% CI: 1.4-26.7).ConclusionsClinical genetic testing of known hereditary thoracic aortic dissection genes should be considered in patients with aortic dissection, followed by cascade screening of family members, especially in patients with age-of-onset of aortic dissection <50 years old, family history of aortic disease, and no history of hypertension.

scholarly journals Delayed Speech and Language in Bardet - Biedl Syndrome

2020 ◽  
pp. 1-2
Author(s):  
Aravinda H R ◽  
◽  
Mohitha Bopaiah ◽  
Keyword(s):  
Genetic Heterogeneity ◽  
Genetic Disorder ◽  
Clinical Spectrum ◽  
Systematic Evaluation ◽  
Many Body ◽  
Speech And Language ◽  
Bardet Biedl Syndrome ◽  
Many Body Systems ◽  
Human Genetic Disorder

Bardet-Biedl Syndrome (BBS) is a human genetic disorder that produces many effects and affects many body systems. The wide clinical spectrum observed in BBS is associated with significant genetic heterogeneity. This article includes a case of Bardet- Biedl syndrome in a 2 years 11 months old girl from Hubli, a town in north Karnataka region of India. A detailed speech, language and hearing profile based on systematic evaluation have been highlighted in the present study

Methemoglobinaemia in Diabetic Ketoacidosis Patient

2021 ◽  
Vol 03 ◽  
Author(s):  
Magdy Mohamed ◽  
Nadem Javed
Keyword(s):  
Ascorbic Acid ◽  
Family History ◽  
Diabetic Ketoacidosis ◽  
G6pd Deficiency ◽  
Genetic Disorder ◽  
Red Blood Cell Transfusion ◽  
Case Presentation ◽  
History Of ◽  
Insulin Dependent ◽  
Glucose 6 Phosphate Dehydrogenase

Background: Glucose-6-phosphate dehydrogenase (G6PD) deficiency is a common X-linked genetic disorder. Case Presentation: In this paper, we report a case of a 41-years-old male patient with non-insulin-dependent diabetes and a family history of G6PD deficiency never known to have any previous hemolytic episodes, presented as a case of diabetic ketoacidosis with features of hemolytic anemia due to G6PD deficiency manifesting as methemoglobinemia and anemia. Conclusion: Our patient successfully managed with ascorbic acid and red blood cell transfusion. Clinicians should, therefore, be aware of the possibility of this uncommon association between diabetic ketoacidosis, G6PD deficiency, and methemoglobinemia which may be present in patients with G6PD deficiency and severe hemolysis.

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