講演情報
[P27-13]頭蓋外胚葉異形成症におけるIFT122の新規病的バリアント
○高橋 宏典1, 永山 志穂1, 木佐美 祥1, 長谷川 冬雪2, 藤原 寛行1, 秦 健一郎3,4 (1.自治医科大学 産科婦人科, 2.国立成育医療研究センター 周産期・母性診療センター, 3.群馬大学 分子細胞生物学, 4.国立成育医療研究センター研究所 周産期病態研究部)
Cranioectodermal dysplasia (CED) type 1,2 is categorized by ciliopathies with major skeletal involvements and autosomal recessive inheritance. The causative gene is intraflagellar transport 122 (IFT122). Here, we detected novel compound heterozygous variants in IFT122. A proband fetus was conceived by naturally. The mother was a 27-year-old Japanese (gestation 4, parous 1), who had no significant familial history. No consanguinity was noted. The first trimester ultrasound showed cystic hygroma and subcutaneous edema of the head, chest and back. The early second trimester ultrasound showed hypoplastic extremities (-3.4 to -5.2SD). The proband fetus was artificially terminated at 19 weeks based on parents’ wish. Post-mortem examination showed hydrops, flat face, short neck, low-set ears, polydactyly of the foot and syndactyly of the 5th/6th digits of the foot. X-ray showed short rib, craniosynostosis, bilateral radial, tibia, fibula and ulna were hypoplastic, bowing of the tibia and fibula. CED was suspected based on the above findings. Trio exome sequencing was performed in the Initiative on Rare and Undiagnosed Diseases. We identified novel compound heterozygous variants in IFT122. The maternal derived-mutation was c.230T＞G (p.V77G). The paternal-derived mutation was c.692A＞T (p.D231V). The two were novel missense mutations. The two variants were considered likely pathogenic according to ACMG guideline. The degree of cystic hygroma and shortened extremities was not mild in this case. The novel variants may show a severe phenotype in CED.