Research press release


Nature Genetics

A genetic clue to a mysterious disorder

診断が難しい疼痛性疾患である関節可動亢進型エーラスダンロス症候群(EDS III)の遺伝的基盤について報告する論文が、今週掲載される。

EDS IIIは、さまざまな疾患の複合体で、説明のつかない複数の症状(例えば、頭痛、体の痛み、皮膚潮紅、激しいかゆみ、胃腸障害)と関節の過可動性という特徴がある。こうした相互に関係がないように見えるさまざまな症状は、症状の間の根本的関係が確定していないため、心理的要因又はその他の要因によるものと考えられる傾向がある。

今回、Joshua Milnerたちは、EDS IIIと一致する遺伝性疾患を持つ米国の96人(35家系)を集めて研究を行った。これらの患者は、免疫応答の一環として産生されるタンパク質であるトリプターゼの血清中濃度が高かったが、それ以外の免疫細胞障害の徴候は見られなかった。Milnerたちは、遺伝子マッピング法と遺伝子コピー数検査を用いて、2種類のトリプターゼのうちの1つ(α-トリプターゼ)をコードする遺伝子(TPSAB1)のコピー数が通常よりも多いことを35家系全てで確認した。TPSAB1遺伝子のコピー数は、上記の症状の重度と相関していた。



The genetic basis of a painful and difficult-to-diagnose disorder is reported in a paper published online this week in Nature Genetics.

Ehlers-Danlos syndrome type III (EDS) is a collection of different disorders characterized by hypermobile joints and multiple unexplained symptoms, such as headache and body pain, skin flushing, severe itching and gastrointestinal problems. These varied and seemingly unrelated symptoms tend to be attributed to psychological or other factors because an underlying relationship between the symptoms has not been established.

Joshua Milner and colleagues recruited 96 individuals from 35 families in the United States with an inherited syndrome consistent with EDS. The patients also had elevated levels of tryptase - a protein produced as part of the immune response - but showed no other signs of immune cell dysfunction. Using genetic mapping methods and a test to look at gene copy numbers, the authors found that all of the families carried extra copies of a gene (TPSAB1) that produces one of the two types of tryptase, called alpha-tryptase. The number of copies of TPSAB1 was correlated with the severity of the symptoms.

The authors then looked at large databases of US patient records and found that, in every case where a patient had elevated serum tryptase levels, the patient also had extra copies of TPSAB1 but had not been diagnosed with EDS or immune cell disease. When the authors interviewed these people, they found that they had symptoms similar to those of the patients in the original study.

These findings may improve the diagnosis of patients with EDS-like symptoms who also have a family history of similar disease and elevated tryptase levels. The authors suggest that future research could explore treatments targeting alpha-tryptase, as complete loss of alpha-tryptase is common and does not cause any known clinical problems.

doi: 10.1038/ng.3696


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