染色体缺失如何揭示隐性突变？与CHAT或SLC18A3突变相关的10q11.2缺失会导致先天性肌无力综合征。

How chromosomal deletions can unmask recessive mutations? Deletions in 10q11.2 associated with CHAT or SLC18A3 mutations lead to congenital myasthenic syndrome.

作者信息

Schwartz Mathias, Sternberg Damien, Whalen Sandra, Afenjar Alexandra, Isapof Arnaud, Chabrol Brigitte, Portnoï Marie-France, Heide Solveig, Keren Boris, Chantot-Bastaraud Sandra, Siffroi Jean-Pierre

机构信息

AP-HP, Département de Génétique Médicale, Hôpital Armand Trousseau, UPMC, Paris, France.

AP-HP, Hôpital Pitié-Salpêtrière, Biochimie et Génétique, Inserm U 1127, CNRS UMR 7225, Sorbonne Universités, UPMC Univ Paris 06 UMR S 1127, ICM, Paris, France.

出版信息

Am J Med Genet A. 2018 Jan;176(1):151-155. doi: 10.1002/ajmg.a.38515. Epub 2017 Nov 12.

DOI:10.1002/ajmg.a.38515

PMID:29130637

Abstract

A congenital myasthenia was suspected in two unrelated children with very similar phenotypes including several episodes of severe dyspnea. Both children had a 10q11.2 deletion revealed by Single Nucleotide Polymorphisms array or by Next Generation Sequencing analysis. The deletion was inherited from the healthy mother in the first case. These deletions unmasked a recessive mutation at the same locus in both cases, but in two different genes: CHAT and SLC18A3.

摘要

两名无血缘关系、具有非常相似表型（包括多次严重呼吸困难发作）的儿童被怀疑患有先天性肌无力。通过单核苷酸多态性阵列或下一代测序分析发现，这两名儿童均存在10q11.2缺失。在第一个病例中，该缺失是从健康母亲那里遗传而来的。在这两个病例中，这些缺失均揭示了同一基因座上的隐性突变，但涉及两个不同的基因：CHAT和SLC18A3。