scholarly journals Challenges in Diagnosing Rare Genetic Causes of Common In Utero Presentations: Report of Two Patients with Mucolipidosis Type II (I-Cell Disease)

2018 ◽  
Vol 07 (03) ◽  
pp. 134-137 ◽  
Author(s):  
Gregory Costain ◽  
Maha Saleh ◽  
Shimrit Yaniv-Salem ◽  
Greg Ryan ◽  
Eric Morgen ◽  
...  
Keyword(s):  
Single Gene ◽  
Genetic Diagnosis ◽  
Type Ii ◽  
Lysosomal Storage ◽  
Cell Disease ◽  
Single Gene Disorders ◽  
Whole Exome ◽  
History Of ◽  
Traditional Approaches ◽  
Mucolipidosis Type

AbstractTraditional approaches to prenatal genetic diagnosis for common presentations such as short femurs or intrauterine growth restriction are imperfect, and whole-exome sequencing is an emerging option. Mucolipidosis type II (I-cell disease) is an ultra-rare autosomal recessive lysosomal storage disorder with the potential for prenatal-onset skeletal and placental manifestations. We describe the prenatal signs in two recent unrelated patients with confirmed diagnoses soon after birth. In both cases, parents were consanguineous but there was no known family history of mucolipidosis type II. False reassurance was provided after negative testing for another disease with overlapping prenatal manifestations already present in one of the families, emphasizing that offspring of consanguineous parents can be at risk for more than one recessive condition. Our experience illustrates the potential advantages in expanding prenatal applications of WES for the identification of rare single gene disorders in offspring of consanguineous unions.

scholarly journals Novel MYO15A variants are associated with hearing loss in the two Iranian pedigrees

2020 ◽  
Vol 21 (1) ◽  
Author(s):  
Somayeh Khatami ◽  
Masomeh Askari ◽  
Fatemeh Bahreini ◽  
Morteza Hashemzadeh-Chaleshtori ◽  
Saeed Hematian ◽  
...  
Keyword(s):  
Hearing Loss ◽  
Exome Sequencing ◽  
Whole Exome Sequencing ◽  
Genetic Diagnosis ◽  
Clinical Genetic ◽  
Large Size ◽  
Whole Exome ◽  
Novel Variants ◽  
Syndromic Hearing Loss ◽  
Traditional Approaches

Abstract Background Clinical genetic diagnosis of non-syndromic hearing loss (NSHL) is quite challenging. With regard to its high heterogeneity as well as large size of some genes, it is also really difficult to detect causative mutations using traditional approaches. One of the recent technologies called whole-exome sequencing (WES) has been thus developed in this domain to remove the limitations of conventional methods. Methods This study was a report on a research study of two unrelated pedigrees with multiple affected cases of hearing loss (HL). Accordingly, clinical evaluations and genetic analysis were performed in both families. Results The results of WES data analysis to uncover autosomal recessive non-syndromic hearing loss (ARNSHL) disease-causing variants was reported in the present study. Initial analysis identified two novel variants of MYO15A i.e. c.T6442A:p.W2148R and c.10504dupT:p.C3502Lfs*15 correspondingly which were later confirmed by Sanger validations and segregation analyses. According to online prediction tools, both identified variants seemed to have damaging effects. Conclusion In this study, whole exome sequencing were used as a first approach strategy to identify the two novel variants in MYO15A in two Iranian families with ARNSHL.

Pathophysiology and therapy for haemoglobinopathies; Part II: thalassaemias

2006 ◽  
Vol 8 (10) ◽  
pp. 1-26 ◽  
Author(s):  
Fabrizia Urbinati ◽  
Catherine Madigan ◽  
Punam Malik
Keyword(s):  
Single Gene ◽  
Globin Gene ◽  
Marrow Transplant ◽  
World Population ◽  
Symptomatic Therapy ◽  
Globin Genes ◽  
Cell Disease ◽  
Critical Function ◽  
Single Gene Disorders ◽  
Clinical Syndromes

Thalassaemias result from mutations of the globin genes that cause reduced or absent haemoglobin production and thus interfere with the critical function of oxygen delivery. They represent the most common single-gene disorders, with 4.83% of the world population carrying globin gene variants. Reduced or absent α-globin (α-thalassaemia) or β-globin (β-thalassaemia) leads to anaemia and multifaceted clinical syndromes. In this second of two reviews on the pathophysiology of haemoglobinopathies, we describe the clinical features, pathophysiology and molecular basis of α- and β-thalassaemias. We then discuss current targeted therapies, including the new oral iron chelators, which, along with chronic transfusions, constitute the mainstay of symptomatic therapy for the majority of patients. Finally, we describe potentially curative therapies, such as bone marrow transplant, and discuss some of the outstanding research studies and questions, including the upcoming field of gene therapy for β-thalassaemia. An accompanying article on haemoglobinopathies (Part I) focuses on sickle cell disease.

Preimplantation genetic diagnosis of single-gene disorders: experience with more than 200 cycles conducted by a reference laboratory in the United States

2009 ◽  
Vol 92 (5) ◽  
pp. 1544-1556 ◽  
Author(s):  
Cristina Gutiérrez-Mateo ◽  
Jorge F. Sánchez-García ◽  
Jill Fischer ◽  
Sophia Tormasi ◽  
Jacques Cohen ◽  
...  
Keyword(s):  
United States ◽  
Preimplantation Genetic Diagnosis ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
The United States ◽  
Reference Laboratory ◽  
Single Gene Disorders

Clinical Spectrum of Mucolipidosis Type IV

PEDIATRICS ◽  
1988 ◽  
Vol 81 (4) ◽  
pp. 602-602
Author(s):  
RAPHAEL WEITZ ◽  
GERTRUDE KOHN
Keyword(s):  
Psychomotor Retardation ◽  
Clinical Spectrum ◽  
Lysosomal Storage ◽  
Motor Delay ◽  
Mucolipidosis Type Iv ◽  
Corneal Clouding ◽  
Type Iv ◽  
History Of ◽  
Corneal Opacities ◽  
Mucolipidosis Type

To the Editor.— We read with interest the presentation by Amir et al1 concerning the clinical spectrum and natural history of mucolipidosis type IV. Based on their experience with 20 patients, they try to provide guidelines for the clinical diagnosis of this lysosomal storage disease. It appears that severe visual impairment (due mainly to corneal opacities, myopia, and retinal degeneration) and psychomotor retardation are the cardinal features of this entity. However, corneal clouding and mild motor delay in their early stages may frequently be missed by even experienced pediatricians and we recently examined a 15-month-old boy who was referred to us for evaluation of a possible congenital myopathy.

scholarly journals Pilot Study of Return of Genetic Results to Patients in Adult Nephrology

2020 ◽  
Vol 15 (5) ◽  
pp. 651-664 ◽  
Author(s):  
Jordan G. Nestor ◽  
Maddalena Marasa ◽  
Hila Milo-Rasouly ◽  
Emily E. Groopman ◽  
S. Ali Husain ◽  
...  
Keyword(s):  
Single Gene ◽  
Qualitative Interviews ◽  
Genetic Diagnosis ◽  
Return Of Results ◽  
Biobank Research ◽  
Single Gene Disorders ◽  
Management Recommendations ◽  
Study Participants ◽  
Improving Patient Care ◽  
Genetic Results

Background and objectivesActionable genetic findings have implications for care of patients with kidney disease, and genetic testing is an emerging tool in nephrology practice. However, there are scarce data regarding best practices for return of results and clinical application of actionable genetic findings for kidney patients.Design, setting, participants, & measurementsWe developed a return of results workflow in collaborations with clinicians for the retrospective recontact of adult nephrology patients who had been recruited into a biobank research study for exome sequencing and were identified to have medically actionable genetic findings.ResultsUsing this workflow, we attempted to recontact a diverse pilot cohort of 104 nephrology research participants with actionable genetic findings, encompassing 34 different monogenic etiologies of nephropathy and five single-gene disorders recommended by the American College of Medical Genetics and Genomics for return as medically actionable secondary findings. We successfully recontacted 64 (62%) participants and returned results to 41 (39%) individuals. In each case, the genetic diagnosis had meaningful implications for the patients’ nephrology care. Through implementation efforts and qualitative interviews with providers, we identified over 20 key challenges associated with returning results to study participants, and found that physician knowledge gaps in genomics was a recurrent theme. We iteratively addressed these challenges to yield an optimized workflow, which included standardized consultation notes with tailored management recommendations, monthly educational conferences on core topics in genomics, and a curated list of expert clinicians for patients requiring extranephrologic referrals.ConclusionsDeveloping the infrastructure to support return of genetic results in nephrology was resource-intensive, but presented potential opportunities for improving patient care.PodcastThis article contains a podcast at https://www.asn-online.org/media/podcast/CJASN/2020_04_16_12481019.mp3

Usage of karyomapping for preimplantation genetic diagnosis (PGD) of complex single gene disorders (sgds)

2014 ◽  
Vol 102 (3) ◽  
pp. e175
Author(s):  
R. Prates ◽  
A. Jordan ◽  
G. Rosen ◽  
M. DiMattina ◽  
S. Chen ◽  
...  
Keyword(s):  
Preimplantation Genetic Diagnosis ◽  
Single Gene ◽  
Genetic Diagnosis ◽  
Single Gene Disorders
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