scholarly journals A Fetus with Congenital Microcephaly, Microphthalmia and Cataract Was Detected with Biallelic Variants in the OCLN Gene: A Case Report

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1576
Author(s):  
Vivian Kwun Sin Ng ◽  
Tze Kin Lau ◽  
Anita Sik Yau Kan ◽  
Brian Hon Yin Chung ◽  
Ho Ming Luk ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Genetic Background ◽  
Congenital Abnormalities ◽  
Whole Genome ◽  
Critical Periods ◽  
Gene Defects ◽  
Environmental Pathogens ◽  
Congenital Microcephaly ◽  
Multiple Congenital Abnormalities

Microcephaly and microphthalmia are both rare congenital abnormalities, while concurrently, these two are even rarer. The underlying etiology would be complex interplaying between heterogeneous genetic background and the environmental pathogens, particularly during critical periods of early tissue development. Here, we reported a prenatal case with microcephaly, microphthalmia, and bilateral cataracts detected by ultrasonography and confirmed by autopsy. Various routine infection-related tests and invasive genetic testing were negative. Whole genome sequencing of fetus and parents revealed OCLN gene defects may be associated with these multiple congenital abnormalities.

scholarly journals Whole-genome amplification/preimplantation genetic testing for propionic acidemia of successful pregnancy in an obligate carrier Mexican couple: A case report

2021 ◽  
Vol 9 (29) ◽  
pp. 8797-8803
Author(s):  
Adina Neumann ◽  
Miguel Angel Alcantara-Ortigoza ◽  
Ariadna González-del Angel ◽  
Nestor Alejandro Zarate Díaz ◽  
Javier Sam Santana ◽  
...  
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Whole Genome Amplification ◽  
Propionic Acidemia ◽  
Whole Genome ◽  
Obligate Carrier ◽  
Successful Pregnancy ◽  
Preimplantation Genetic Testing ◽  
Genome Amplification

scholarly journals Biallelic Variants in LAMB1 Causing Hydranencephaly: A Severe Phenotype of a Rare Malformative Encephalopathy

2021 ◽  
Vol 11 (01) ◽  
pp. e26-e28
Author(s):  
Kuntal Sen ◽  
Shagun Kaur ◽  
David W. Stockton ◽  
Mary Nyhuis ◽  
Jacquelyn Roberson
Keyword(s):  
Case Report ◽  
Genetic Testing ◽  
Genome Sequencing ◽  
Whole Genome ◽  
Severe Phenotype ◽  
Genetic Etiology ◽  
Dysmorphic Features ◽  
Phenotypic Spectrum ◽  
History Of ◽  
Cobblestone Lissencephaly

Abstract Case Report A 32-year-old female with a history of three prior pregnancy losses presented for genetic testing following an ultrasonography diagnosis of fetal hydranencephaly. Baby was born via C-section and was noted to have a head circumference of 48 cm, in addition to ocular and cardiac anomalies and dysmorphic features. Whole genome sequencing revealed a homozygous variant in LAMB1 gene. Discussion The pathobiogenesis of hydranencephaly is incompletely understood and is attributed to vascular, infectious, or genetic etiology. Herein we present LAMB1 as a monogenic cause of fetal hydranencephaly which was incompatible with life. Previously, LAMB1-associated phenotype consisted of cobblestone lissencephaly and hydrocephalus, developmental delay, and seizures. Our proband expands the phenotypic spectrum of this malformative encephalopathy.

scholarly journals R1352Q CACNA1A Variant in a Patient with Sporadic Hemiplegic Migraine, Ataxia, Seizures and Cerebral Oedema: A Case Report

2021 ◽  
pp. 123-130
Author(s):  
Anker Stubberud ◽  
Emer O’Connor ◽  
Erling Tronvik ◽  
Henry Houlden ◽  
Manjit Matharu
Keyword(s):  
Mental Retardation ◽  
Case Report ◽  
Genetic Testing ◽  
Head Trauma ◽  
Cerebral Oedema ◽  
De Novo ◽  
Minor Head Trauma ◽  
Hemiplegic Migraine ◽  
Wide Range ◽  
History Of

Mutations in the <i>CACNA1A</i> gene show a wide range of neurological phenotypes including hemiplegic migraine, ataxia, mental retardation and epilepsy. In some cases, hemiplegic migraine attacks can be triggered by minor head trauma and culminate in encephalopathy and cerebral oedema. A 37-year-old male without a family history of complex migraine experienced hemiplegic migraine attacks from childhood. The attacks were usually triggered by minor head trauma, and on several occasions complicated with encephalopathy and cerebral oedema. Genetic testing of the proband and unaffected parents revealed a de novo heterozygous nucleotide missense mutation in exon 25 of the <i>CACNA1A</i> gene (c.4055G&#x3e;A, p.R1352Q). The R1352Q <i>CACNA1A</i> variant shares the phenotype with other described <i>CACNA1A</i> mutations and highlights the interesting association of trauma as a precipitant for hemiplegic migraine. Subjects with early-onset sporadic hemiplegic migraine triggered by minor head injury or associated with seizures, ataxia or episodes of encephalopathy should be screened for mutations. These patients should also be advised to avoid activities that may result in head trauma, and anticonvulsants should be considered as prophylactic migraine therapy.

scholarly journals Bilateral Congenital Humeroradial Synostostis Presenting with Bilateral Proximal Radius Fractures: A Case Report

2021 ◽  
pp. 29-32
Author(s):  
Elsiddig E. Mahmoud
Keyword(s):  
Case Report ◽  
Elbow Joint ◽  
Parental Education ◽  
Functional Disability ◽  
Congenital Abnormalities ◽  
Rare Condition ◽  
Radius Fractures ◽  
Proximal Radius ◽  
History Of ◽  
Uncommon Condition

Congenital bilateral humeroradial synostosis (HRS) is a rare condition. It is generally divided into 2 categories. In the first group, which is mainly sporadic, additional upper limb hypoplasia typically coexists. In the second group, which is classically familial, HRS is commonly an isolated upper extremity anomaly. HRS can lead to variable degrees of functional disability. The clinical case reported here illustrates a possibly avoidable presentation of this uncommon condition. In this case report, we present a 6-week-old male who presented with bilateral radius fractures. Radiography revealed congenital HRS at both elbows. No other associated congenital abnormalities were detected, and there was no family history of similar conditions in any first-degree relatives. In cases of congenital HRS, movement at the elbow joint is not possible. Parents who are unaware of this information might try to straighten their infant’s elbows, which in turn may result in fractures of the proximal radius. Hence, early diagnosis and proper parental education could prevent fractures as a sequela of HRS.

scholarly journals Continuing the sequence? Towards an economic evaluation of whole genome sequencing for the diagnosis of rare diseases in Scotland

2021 ◽  
Author(s):  
Michael Abbott ◽  
Lynda McKenzie ◽  
Blanca Viridiana Guizar Moran ◽  
Sebastian Heidenreich ◽  
Rodolfo Hernández ◽  
...  
Keyword(s):  
Economic Evaluation ◽  
Genetic Testing ◽  
Whole Genome Sequencing ◽  
Genome Sequencing ◽  
Rare Diseases ◽  
Genomic Medicine ◽  
Future Research ◽  
Clinical Genetics ◽  
Whole Genome ◽  
Peace Of Mind

AbstractNovel developments in genomic medicine may reduce the length of the diagnostic odyssey for patients with rare diseases. Health providers must thus decide whether to offer genome sequencing for the diagnosis of rare conditions in a routine clinical setting. We estimated the costs of singleton standard genetic testing and trio-based whole genome sequencing (WGS), in the context of the Scottish Genomes Partnership (SGP) study. We also explored what users value about genomic sequencing. Insights from the costing and value assessments will inform a subsequent economic evaluation of genomic medicine in Scotland. An average cost of £1,841 per singleton was estimated for the standard genetic testing pathway, with significant variability between phenotypes. WGS cost £6625 per family trio, but this estimate reflects the use of WGS during the SGP project and large cost savings may be realised if sequencing was scaled up. Patients and families valued (i) the chance of receiving a diagnosis (and the peace of mind and closure that brings); (ii) the information provided by WGS (including implications for family planning and secondary findings); and (iii) contributions to future research. Our costings will be updated to address limitations of the current study for incorporation in budget impact modelling and cost-effectiveness analysis (cost per diagnostic yield). Our insights into the benefits of WGS will guide the development of a discrete choice experiment valuation study. This will inform a user-perspective cost–benefit analysis of genome-wide sequencing, accounting for the broader non-health outcomes. Taken together, our research will inform the long-term strategic development of NHS Scotland clinical genetics testing services, and will be of benefit to others seeking to undertake similar evaluations in different contexts.

P–540 A feasible diagnostic approach for the cryptic subtelomeric traslocations in early recurrent miscarriage patients by preimplantation genetic testing (PGT)

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
B Lledo ◽  
R Morales ◽  
J A Ortiz ◽  
A Cascales ◽  
A Fabregat ◽  
...  
Keyword(s):  
Genetic Testing ◽  
Recurrent Miscarriage ◽  
Chromosome Translocation ◽  
Accurate Diagnosis ◽  
Molecular Techniques ◽  
Telomeric Region ◽  
Whole Genome ◽  
Preimplantation Genetic Testing ◽  
Uterine Anomalies ◽  
Cryptic Translocation

Abstract Study question Could cryptic subtelomeric traslocations in early recurrent miscarriage patients be diagnosed by preimplantation genetic testing? Summary answer PGT is a powerful tool to detect subtelomeric cryptic traslocations identifying the cause of early recurrent miscarriage and allowing subsequent genetic counselling. What is known already: Chromosome translocations are frequently associated with birth defects, spontaneous early pregnancy losses and infertility. However, submicroscopic traslocations (so-called cryptic traslocations) are too small to be detected by conventional karyotyping.. Due to balanced status, high resolution molecular techniques as arrayCGH are not able to detect it. Thus, cryptic traslocations detection is challenging. PGT is able to detect CNVs at higher resolution than routine karyotyping. Therefore, the recurrent diagnosis of CNV at embryo level could suggest a subchromosomal parental traslocation. The aim of this study is to investigate the feasibility of using PGT as an indicator of parental balanced cryptic traslocations. Study design, size, duration We included three couples who underwent PGT for unexplained repeated pregnancy loss (RPL) in our clinic from February 2020 to November 2020. Common established causes of RPL (uterine anomalies, antiphospholipid syndrome, immunological, hormonal and metabolic disorders) were previously rouled-out. Even couple karyotypes were normal. Twenty-three embryos from those couples were biopsied at blastocyst and analysed for CNVs detection using low coverage whole genome NGS. Participants/materials, setting, methods PGT by NGS was performed by Veriseq-NGS (Illumina), with previous whole genome amplification. Fluorescence in situ hybridization (FISH) using parental blood samples were performed to validate the origin of subchromosomal number variation. Commercially available subtelomeric specific probes were selected according to the CNV identified and the procedures were performed according to the manufacturer’s protocols. Main results and the role of chance Overall, CNVs of terminal duplication and deletion that imply unbalanced traslocation derivatives were detected in the 43.5% of biopsied embryos. For couple 1, 4 out of 5 embryos (80%) carried deletion of telomeric region on chromosomes 5 and 21. Three out of 6 biopsed embyos (50%) were diagnosed with subchromosomal copy variants at telomeric region on chromosomes 6 and 16 for couple 2. In the case of couple 3, three out of 12 embryos (25%) were carriers of CNV at subtelomeric region on chromosomes 2 and 6. The size of CNVs detected ranges from 8Mb to 20Mb. Accurate diagnosis with the parental study was made by FISH. The combination of probes to detect the structural chromosome alteration were: Tel5qter-LSI21q, Tel6pter-CEP16 and Tel6pter-CEP6 for each couple respectively. The FISH studies reveal that CNVs were inherited from one parent carrying the balanced cryptic traslocation. Ultimately, the abnormal karyotype from the carrier parent were 46,XY,t(5;21)(q33.2;q21.2) for couple 1, 46,XY,t(6;16)(p22.3;q22.1) for couple 2 and 46,XY,t(2;6)(p25.1;p24.2) for couple 3. Finally, each couple performed a cryotransfer of a single normal balanced embryo. Two pregnancies are ongoing. Limitations, reasons for caution The main limitation of this approach is the NGS- PGT resolution. CNVs smaller than 5Mb could not be detected. Wider implications of the findings: This study shows the value of PGT for unexplained RPL, followed by parental FISH to better characterize CNVs and identify couples in whom one partner carries a cryptic translocation. Accurate diagnosis of parental chromosome translocation can achieve with FISH only, but FISH would not be performed unless PGT showed CNVs. Trial registration number Not applicable

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