中国のある家族におけるホモ接合型-関連性遺伝性出血性毛細血管拡張症

Homozygous -Related Hereditary Hemorrhagic Telangiectasia in a Chinese Family.

• Jinrong Liu
• Jigang Yang
• Xiaolei Tang
• Huimin Li
• Yuelin Shen
• Weiyue Gu
• Shunying Zhao

抄録

遺伝性出血性毛細血管拡張症（HHT）は臨床的に診断可能であるが，小児には特徴的な特徴がないことが多い．我々は、遺伝子検査で診断されたホモ接合性成長分化因子2()関連のHHTを有する一家を報告する。5歳2ヶ月の男児が単発性低酸素血症を呈した。両親は2番目のいとこであった．身体所見では爪床のチアノーゼと指のクラブ状節理が認められた．脈拍酸素飽和度は84～89％であった．肺機能，造影肺CT，非造影心エコーは正常であった．肺灌流スキャンでは脳と両側の腎臓に放射能が検出され、肺内シャントの存在を示唆していた。全ゲノムシークエンシングの結果、ヘテロ接合の両親から遺伝することが判明した。8歳の時，鼻出血を発症し，血管造影検査でびまん性肺動静脈奇形が認められた．9歳の時にシロリムスが投与され，症状は著しく改善した．しかし，同じホモ接合型を持つ7歳になる妹には現在症状がなかった．身体検査の結果，母親の胸部にピンポイントサイズの毛細血管拡張症が1個，妹の額に血管病変が認められた．さらに，この患者の父と大叔父には軽度から中等度の鼻出血の既往歴があった．HHTの原因となる変異はまれである。我々の報告は、ホモ接合体-関連のHHTの最初の報告であり、また、この変異はこれまでに報告されていない。我々の報告では、同じ病原性を持つ-related HHTの変異体であっても、発現が異なることも確認されています。

Hereditary hemorrhagic telangiectasia (HHT) can be clinically diagnosed, but children often lack characteristic features. We report a family with homozygous growth differentiation factor 2 ()-related HHT diagnosed by genetic testing. A boy aged 5 years and 2 months presented with isolated hypoxemia. He was the product of a consanguineous marriage; his parents were second cousins. Physical examination revealed cyanosis of nail beds and clubbed fingers. Pulse oxygen saturation was 84% to 89%. Lung function, contrast-enhanced lung computed tomography, and noncontrast echocardiography were normal. A pulmonary perfusion scan revealed radioactivity in the brain and bilateral kidney, suggesting the existence of a intrapulmonary shunt. Whole-exome sequencing revealed a homozygous variant [c.1060_1062delinsAG (p.Tyr354ArgfsTer15)] in , which was found to be inherited from his heterozygous parents. At the age of 8 years, he developed epistaxis, and an angiogram revealed diffuse pulmonary arteriovenous malformations. At the age of 9 years, he was treated with sirolimus, and his condition improved significantly. However, his now 7-year-old sister with the same homozygous variant currently has no symptoms. Physical examinations revealed 1 pinpoint-sized telangiectasia on the chest of his mother and a vascular lesion on the forehead of his sister. Additionally, the patient's father and great-uncle had a history of mild to moderate epistaxis. Mutation in is a rare cause of HHT. Ours is the first report of homozygous -related HHT; in addition, this variant has not been reported previously. In our report, we also confirm variable expressivity, even with the same pathogenic variant in -related HHT.

Copyright © 2020 by the American Academy of Pediatrics.