講演情報
[O24-2]Whole genome sequencing resolved a whole exome negative patient with congenital ichthyosis and severe atopic dermatitis
○柳 久美子1, 佐藤 未織2, 比田井 朋美1, 小俣 牧子1, 佐藤 万仁1, 山毛利 雅彦1, 五十嵐 ありさ1, 青木 大芽1, 飯田 貴也1, 寒竹 正人3, 馬場 洋介4, 宮林 和紀4, 田中 諒6, 吉田 和恵2,6, 野村 伊一郎2,5, 大矢 幸弘2, 松原 洋一7, 要 匡1 (1.国立成育医療研究センター ゲノム医療研究部, 2.国立成育医療研究センター アレルギーセンター, 3.順天堂大学医学部附属練馬病院 新生児科, 4.順天堂大学医学部附属静岡病院 小児科, 5.国立成育医療研究センター 好酸球性消化管疾患研究室, 6.国立成育医療研究センター 皮膚科, 7.国立成育医療研究センター)
Whole exome sequencing (WES) analysis provides great success in identifying pathogenic variants in rare diseases and undiagnosed patients. However, more than half of such patients performed by WES analysis still remain undiagnosed. Here, we report a case in which the causative variants, which were unsolved by WES analysis, were successfully identified by whole genome sequencing (WGS) analysis, leading to a diagnosis. The affected proband was an 8-month-old boy born to non-consanguineous parents. He had congenital ichthyosis, severe atopic dermatitis, erythroderma and gastrointestinal allergy. He also showed poor weight gain and failure to thrive. His brother had similar symptoms and died because of recurrent infection in late infancy. After obtaining written informed consent, trio-WES analysis was performed, which revealed candidate causative variants, heterozygotes variants of SPINK5:NM_006846:c.2468dup:p.(Lys824Glufs*4) and CYP4F22:NM_173483.4:c.850C＞T:p.(Arg284Trp) from his father and mother, respectively. However, since those are responsible for autosomal recessive diseases, diagnosis could not be made. Thus, we performed WGS analysis. The WGS anslysis revealed an about 1.8 kb deletion including one exon in addition to the c.2468dup in SPINK5. The deletion was from his mother. Hair abnormalities (bamboo hair) were clinically observed in the patient, and he was finally diagnosis as Netherton syndrome.WGS analysis covers a wider detection range of variants than WES analysis and is more useful to identify causative variants in such rare diseases and undiagnosed patients.