肥大型心筋症は、この遺伝子に変異があると常染色体劣性型の肥大型心筋症を引き起こす

Mutations in cause an autosomal-recessive form of hypertrophic cardiomyopathy.

• Joel Salazar-Mendiguchía
• Juan Pablo Ochoa
• Julian Palomino-Doza
• Fernando Domínguez
• Carles Díez-López
• Mohammed Akhtar
• Soraya Ramiro-León
• María M Clemente
• Antonia Pérez-Cejas
• María Robledo
• Iria Gómez-Díaz
• María Luisa Peña-Peña
• Vicente Climent
• Francisco Salmerón-Martínez
• Celestino Hernández
• Pablo E García-Granja
• M Victoria Mogollón
• Ivonne Cárdenas-Reyes
• Marcos Cicerchia
• Diego García-Giustiniani
• Arsonval Lamounier
• Belén Gil-Fournier
• Felícitas Díaz-Flores
• Rafael Salguero
• Luis Santomé
• Petros Syrris
• Montse Olivé
• Pablo García-Pavía
• Martín Ortiz-Genga
• Perry M Elliott
• Lorenzo Monserrat

抄録

目的:

肥大型心筋症（HCM）患者の 50%までは、遺伝学的研究では疾患の原因となる変異を認めていない。我々は、この遺伝子の希少な変異体とHCMの発症との関係を調べようとした。

OBJECTIVE: Up to 50% of patients with hypertrophic cardiomyopathy (HCM) show no disease-causing variants in genetic studies. has been suggested as a candidate gene for the development of cardiomyopathies, although evidence for a causative role in HCM is limited. We sought to investigate the relationship between rare variants in and the development of HCM.

方法:

HCMの臨床診断を受けたインデックス症例4867例と、他の心筋症を有する3628例のプロバントにおいて、次世代シークエンシングにより、HCMの遺伝子配列が決定された。また、心筋症以外の家族性心血管系疾患（主にチャンネル病と大動脈疾患）を有する3136例を対照とした。

METHODS: was sequenced by next generation sequencing in 4867 index cases with a clinical diagnosis of HCM and in 3628 probands with other cardiomyopathies. Additionally, 3136 index cases with familial cardiovascular diseases other than cardiomyopathy (mainly channelopathies and aortic diseases) were used as controls.

結果:

稀なホモ接合体または複合ヘテロ接合体の変異（HCM15例、制限性心筋症1例）を有する16例の指標症例を対象とした。対照集団ではホモ接合体または複合ヘテロ接合体は確認されなかった。家族評価では、ホモ接合体と複合ヘテロ接合体のみに疾患の徴候が認められたが、ヘテロ接合体の家族はすべて健康であった。診断時の平均年齢は35歳（範囲15～69歳）であった。患者の50％は同心性左室肥大（LVH）を有し、45％は初診時に無症状であった。晩期のガドリニウム増強は80％の患者に認められ、20％の患者に左室（LV）収縮機能障害が認められた。50％の患者には非持続性心室頻拍が認められた。20％の患者が有害な脳血管イベントを発症した（20％）。

RESULTS: Sixteen index cases with rare homozygous or compound heterozygous variants in (15 HCM and one restrictive cardiomyopathy) were included. No homozygous or compound heterozygous were identified in the control population. Familial evaluation showed that only homozygous and compound heterozygous had signs of disease, whereas all heterozygous family members were healthy. The mean age at diagnosis was 35 years (range 15-69). Fifty per cent of patients had concentric left ventricular hypertrophy (LVH) and 45% were asymptomatic at the moment of the first examination. Significant degrees of late gadolinium enhancement were detected in 80% of affected individuals, and 20% of patients had left ventricular (LV) systolic dysfunction. Fifty per cent had non-sustained ventricular tachycardia. Twenty per cent of patients suffered an adverse cerebrovascular event (20%).

結論:

は常染色体劣性遺伝する HCM のまれな原因であり，同心円状 LVH と高率の LV 機能障害を伴う．

CONCLUSION: appears to be an uncommon cause of HCM inherited in an autosomal-recessive manner and associated with concentric LVH and a high rate of LV dysfunction.

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