The benefits and challenges of family genetic testing in rare genetic diseases—lessons from Fabry disease

Germain, Dominique P.; Moiseev, Sergey; Süárez-Obando, Fernando; Ismaili, Faisal Al; Khawaja, Huda Al; Altarescu, Gheona; Barreto, Fellype Carvalho; Haddoum, F.; Hadipour, Fatemeh; Maksimova, I. A.; Kramis, Mirelle; Nampoothiri, Sheela; Nguyen, Khanh Ngoc; Niu, Dau‐Ming; Politei, Juan; Ro, Long‐Sun; Vu, Dung; Chen, Nan; Kutsev, Sergey I.

doi:10.1002/mgg3.1666

Cited by 31 publications

(16 citation statements)

References 78 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Moreover, their identification allows physicians to perform cascade genotyping in at risk family members and identify undiagnosed relatives [69]. Furthermore, NBS will help to better understand the natural course of the disease.…”

Section: Biomarkers and Biochemicalmentioning

confidence: 99%

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Gragnaniello¹,

Polo²,

Giuliani³

et al. 2021

Biomolecules

Self Cite

View full text Add to dashboard Cite

Fabry disease (FD) is a progressive multisystemic lysosomal storage disease. Early diagnosis by newborn screening (NBS) may allow for timely treatment, thus preventing future irreversible organ damage. We present the results of 5.5 years of NBS for FD by α-galactosidase A activity and globotriaosylsphingosine (lyso-Gb3) assays in dried blood spot through a multiplexed MS/MS assay. Furthermore, we report our experience with long-term follow-up of positive subjects. We screened more than 170,000 newborns and 22 males were confirmed to have a GLA gene variant, with an incidence of 1:7879 newborns. All patients were diagnosed with a variant previously associated with the later-onset phenotype of FD or carried an unclassified variant (four patients) or the likely benign p.Ala143Thr variant. All were asymptomatic at the last visit. Although lyso-Gb3 is not considered a reliable second tier test for newborn screening, it can simplify the screening algorithm when its levels are elevated at birth. After birth, plasma lyso-Gb3 is a useful marker for non-invasive monitoring of all positive patients. Our study is the largest reported to date in Europe, and presents data from long-term NBS for FD that reveals the current incidence of FD in northeastern Italy. Our follow-up data describe the early disease course and the trend of plasma lyso-Gb3 during early childhood.

show abstract

Section: Biomarkers and Biochemicalmentioning

confidence: 99%

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Gragnaniello¹,

Polo²,

Giuliani³

et al. 2021

Biomolecules

Self Cite

View full text Add to dashboard Cite

show abstract

“…Once a genetic diagnosis is achieved, patients need support to understand not only the implications of this verdict and the real meaning of carrying a genetic abnormality but also, and sometimes more importantly, to grief and to adapt to all psychosocial aspects involved [ 9 , 12 , 13 ]. Furthermore, genetics is shared among the family having implications for the closer relatives accounting for their risk of carrying a disease-causing variant [ 14 ]. These disease-causing genetic changes might be passed from one generation to the next, although for rare disorders they also might occur de novo, with the patient being the first affected person in the family [ 15 , 16 , 17 ].…”

Section: The Role Of Genetic Counselling For Rare Diseasesmentioning

confidence: 99%

“…However, there are still challenges for the application of cascade genetic testing, such as cost, cultural and social issues, communication (including reduced access to genetic counsellors) and logistic issues (including lack of genetic specialists or the geographical location). For example, living in a different region than the patient testing positive might make family screening of relatives difficult and unequal access to genetics services will also complicate cascade testing [ 13 , 14 , 20 ]. Furthermore, for some genetic diseases, inheritance patterns and mechanisms of disease are complex and require genetic specialists enriched with communication skills to help families understand the genetic cause and implications for the family [ 21 ].…”

Section: The Role Of Genetic Counselling For Rare Diseasesmentioning

confidence: 99%

Current Status of Genetic Counselling for Rare Diseases in Spain

et al. 2021

View full text Add to dashboard Cite

Genetic Counselling is essential for providing personalised information and support to patients with Rare Diseases (RD). Unlike most other developed countries, Spain does not recognize geneticists or genetic counsellors as healthcare professionals Thus, patients with RD face not only challenges associated with their own disease but also deal with lack of knowledge, uncertainty, and other psychosocial issues arising as a consequence of diagnostic delay. In this review, we highlight the importance of genetic counsellors in the field of RD as well as evaluate the current situation in which rare disease patients receive genetic services in Spain. We describe the main units and strategies at the national level assisting patients with RD and we conclude with a series of future perspectives and unmet needs that Spain should overcome to improve the management of patients with RD.

show abstract

“…In many high-risk screenings for FD, GLA sequencing was performed on family members of the proband, and many cases of FD have been diagnosed by family analysis [124].…”

Section: Gla Sequencing and Genetic Counseling For Families Of Patients With Fdmentioning

confidence: 99%

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

et al. 2021

View full text Add to dashboard Cite

Fabry disease (FD) is an X-linked inherited disorder caused by mutations in the GLA gene, which encodes the lysosomal enzyme α-galactosidase A (α-Gal A). FD detection in patients at an early stage is essential to achieve sufficient treatment effects, and high-risk screening may be effective. Here, we performed high-risk screening for FD in Japan and showed that peripheral neurological manifestations are important in young patients with FD. Moreover, we reviewed the literature on high-risk screening in patients with renal, cardiac, and central neurological manifestations. Based on the results of this study and review of research abroad, we believe that FD can be detected more effectively by targeting individuals based on age. In recent years, the methods for high-risk screening have been ameliorated, and high-risk screening studies using GLA next-generation sequencing have been conducted. Considering the cost-effectiveness of screening, GLA sequencing should be performed in individuals with reduced α-Gal A activity and females with certain FD manifestations and/or a family history of FD. The findings suggest that family analysis would likely detect FD patients, although GLA sequencing of asymptomatic family members requires adequate genetic counseling.

show abstract

The benefits and challenges of family genetic testing in rare genetic diseases—lessons from Fabry disease

Abstract: This is an open access article under the terms of the Creat ive Commo ns Attri butio n-NonCo mmerc ial-NoDerivs License, which permits use and distribution in any medium, provided the original work is properly cited, the use is non-commercial and no modifications or adaptations are made.

Cited by 31 publications

References 78 publications

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Newborn Screening for Fabry Disease in Northeastern Italy: Results of Five Years of Experience

Current Status of Genetic Counselling for Rare Diseases in Spain

High-Risk Screening for Fabry Disease: A Nationwide Study in Japan and Literature Review

Contact Info

Product

Resources

About