講演情報
[O23-4]母由来のPORCNミスセンス変異を同定した46,XY男児のPORCN non-Goltz spectrumの1例
○長崎 啓祐1, 深堀 響子1, 矢本 香織2, 才津 浩智2, 緒方 勤3 (1.新潟大学医歯学総合病院 小児科, 2.浜松医科大学 医化学講座, 3.浜松医科大学 小児科)
【Background】Although germline-derived pathogenic variants in PORCN on Xp11.23 are known to cause focal dermal hypoplasia (FDH) recognized as an X-linked dominant male-lethal disorder, recent studies have revealed that several germline-derived PORCN variants lead to an X-linked recessive disorder, with abnormal phenotype in hemizygous males and normal phenotype in heterozygous females. Happle has proposed a novel disease entity PORCN non-Goltz spectrum (PONGOS) for this condition. We report a Japanese patient with PONGOS.【Case】Proband was found to have bilateral microphthalmia, limb malformations, and bilateral cryptorchidism. He showed growth failure, developmental delay, and hypotonia. On the last examination at 10.8 years of age, he measured 109.4 cm (-4.9 SD) and weighed 12.9 kg (-8.5 SD). He could stand by himself but was unable to walk without support. Notably, no skin lesion was identified in this patient. The mother was free from abnormal phenotype including ocular and limb lesions. Whole exome sequencing was carried out, identifying a maternally inherited hemizygous variant of PORCN (c.368T＞(G:p.(Met123Arg)). In addition, X chromosome inactivation pattern showing random X-inactivation in the mother.【Discussion & Conclusion】FDH and PONGOS could be regarded as continuous entities involved in a single clinical spectrum rather than as distinctive disorders. Indeed, clinical features would primarily be determined by the degree of residual functions of PORCN variants in both males and females and by the X-inactivation pattern of each organ in females.