Идёт набор NCT07332702

Long Read Analysis in Spinal Muscular Atrophy - LOREASI

Без фазы С лечением Spinal Muscular Atrophy (SMA)

Ориентир для пациента и семьи

Простыми словами

Автоматическая сводка по структурированным данным реестра. Она помогает сориентироваться, но не заменяет официальный протокол или оценку врача.

Что изучают: В протоколе указаны: blood sample.
Кому может быть актуально: Состояния в реестре: Spinal Muscular Atrophy (SMA). Базовые параметры: от 18 лет · Все.
Что важно проверить: Возраст, диагноз и пол — только базовые ориентиры. Предыдущее лечение, анализы и другие обязательные условия указаны ниже в критериях участия.
Где проводится: Франция
Следующий шаг: Сохраните исследование, покажите его лечащему врачу и уточните актуальный статус у исследовательского центра. Расходы, документы и поездка →

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Официальное название

Detection of Cis Duplications of the SMN1 Gene Using Long-read Analysis to Address a Major Issue in Genetic Counseling for Spinal Muscular Atrophy

Обзор

Spinal Muscular Atrophy (SMA) is a severe neuromuscular disease caused by deletion of the SMN1 gene, with the most severe form leading to death in children without treatment. Genetic counselling to detect couples where both partners are carriers is particularly important. In some countries, preconception screening is offered. However, some carriers escape detection due to the existence of two copies of the SMN1 gene side-by-side (2+0 genotype). Currently, no molecular genetic methods used for diagnostic purposes can detect these 2+0 genotypes, which pose a significant challenge in genetic counselling. This study aims to use new technologies based on the analysis of ultra-long molecules to detect side-by-side duplications of the SMN1 gene to detect heterozygous subjects not identified by current techniques and improve genetic counselling.

Подробное описание

Spinal Muscular Atrophy (SMA) is a severe autosomal recessive neuromuscular disease, with the most severe form leading to death in children without treatment. Genetic counseling to detect couples where both partners are heterozygous is particularly important. In some countries, preconception screening is offered. However, some individuals' heterozygous status escape detection due to the existence of a cis duplication of the SMN1 gene on the second allele (\[2+0\] genotype). Currently, no molecular genetic methods used for diagnostic purposes can detect these \[2+0\] genotypes, which poses a significant challenge in genetic counseling.

The SMN1 gene, responsible for SMA, is located in the 5q11q13 region, which remains poorly understood in the human reference genome ("dark region"). The architecture of this inverted duplicated region favors recombination events that lead to deletions, duplications, and gene conversions. The SMN1 gene, located in the telomeric region, has a very homologous copy, the SMN2 gene, located in the centromeric region. The lack of detailed knowledge about duplication events hinders the development of molecular tools aimed at improving genetic counseling.

This study aims to use new technologies based on the analysis of ultra-long molecules to detect cis duplication of the SMN1 gene. We will assess the usefulness of optical mapping (Bionano) to analyze this complex region.

Вмешательства

Генная терапия blood sample
For subjects who agree to participate in the study, a blood sample will be taken (2x5 mL on EDTA) and sent the same day at 4°C to the genetics laboratory at Rouen University Hospital using a carrier that guarantees delivery on D+1

Первичные конечные точки

Ability to identify a [2+0] SMN1 genotype [Срок оценки: From enrollment until the end of the analyses (36 months)]

Вторичные конечные точки (1)

Ability to perform assembly of ultra-long molecules of DNA [Срок оценки: From enrollment until the end of the analyses (36 months)]

Критерии участия

Критерии включения

Adult Subject:

Subject with either:

1 or 3 copies of the SMN1 gene (control group) and a variable number of copies of the SMN2 gene
2 copies of the SMN1 gene in cis (2+0 genotype) (test group)
Affiliation to French health insurance
Signed consent form