講演情報
[O24-1]スプライス異常が同定されたfocal dermal hypoplasiaの家族例
○矢本 香織1,2, 岡田 賢3, 加藤 芙弥子4, 藤澤 泰子2, 深見 真紀5, 才津 浩智1, 緒方 勤1,2,6 (1.浜松医科大学 医化学講座, 2.浜松医科大学 小児科, 3.広島大学 小児科, 4.浜松成育医療学講座, 5.国立成育医療センター 分子内分泌研究部, 6.浜松医療センター 小児科)
Background: Whole exome sequencing (WES) can identify sequence variants not only on exons and their splice sites but also on a certain extent of intronic sequences from the splice sites. Recently, developed splice prediction tools have served for the detection of alternative splice sites created by intronic variants.
Case report: Two females in a family had focal dermal hypoplasia-like phenotypes. The proband was a 42-year-old female with hyperpigmentation, ridged dysplastic nails, ectrodactyly, and enamel hypoplasia. Her 4-year-old daughter exhibited hyperpigmentation, ridged dysplastic nails, and cutaneous syndactyly.
Molecular studies: WES revealed a novel PORCN intronic variant (NM_203475.3:c.374-16T＞G) in a mother and her daughter. This variant was predicted to create an alternative splice acceptor site by splice prediction tools (SpliceAI, ESEfinder, and NetGene2), and the occurrence of aberrant splicing resulting in an in-frame 15 bp insertion was confirmed by sequencing of the RT-PCR products. Additionally, an extremely small amount of variant mRNA and a severely skewed inactivation of the X chromosome carrying the variant were shown in the mother.
Conclusions: The results imply the usefulness of WES, which can identify intronic variant and in silico splice prediction tools in the detection of pathogenic intronic variants affecting splicing. Furthermore, small amount of variant mRNA observed in the mother suggests that leukocytes expressing the pathogenic PORCN variant were gradually eliminated with age because of the reduced viability.
Case report: Two females in a family had focal dermal hypoplasia-like phenotypes. The proband was a 42-year-old female with hyperpigmentation, ridged dysplastic nails, ectrodactyly, and enamel hypoplasia. Her 4-year-old daughter exhibited hyperpigmentation, ridged dysplastic nails, and cutaneous syndactyly.
Molecular studies: WES revealed a novel PORCN intronic variant (NM_203475.3:c.374-16T＞G) in a mother and her daughter. This variant was predicted to create an alternative splice acceptor site by splice prediction tools (SpliceAI, ESEfinder, and NetGene2), and the occurrence of aberrant splicing resulting in an in-frame 15 bp insertion was confirmed by sequencing of the RT-PCR products. Additionally, an extremely small amount of variant mRNA and a severely skewed inactivation of the X chromosome carrying the variant were shown in the mother.
Conclusions: The results imply the usefulness of WES, which can identify intronic variant and in silico splice prediction tools in the detection of pathogenic intronic variants affecting splicing. Furthermore, small amount of variant mRNA observed in the mother suggests that leukocytes expressing the pathogenic PORCN variant were gradually eliminated with age because of the reduced viability.