Gana Simone, Piccinni Luisa, Rognone Elisa, Beverino Alessia, Varesio Costanza, Asaro Alessia, Pichiecchio Anna, Valente Enza Maria
Neurogenetics Research Center, IRCCS Mondino Foundation, Pavia, Italy.
Department of Brain and Behavioural Sciences, University of Pavia, Pavia, Italy.
Neurogenetics. 2025 Jun 30;26(1):53. doi: 10.1007/s10048-025-00832-9.
RASopathies are a wide group of multisystemic disorders caused by pathogenic variants in genes belonging to the RAS/MAPK pathway. Among these, PPP1CB gene variants cause Noonan syndrome-like disorder with loose anagen hair 2 (NSLAH2), a rare condition with neuro-cardio-facio-skeletal involvement and the peculiar loose anagen hair. We report on a girl carrying the recurrent c.146 C > G (p.Pro49Arg) pathogenic variant, who presented the classical NSLH features associated with a previously unreported complete commissural agenesis, likely expanding the phenotype. The prominent role of Ras protein in oligodendrocyte maturation and differentiation might lend biological plausibility to the myelination impairment observed in our patient.
RAS 病是由 RAS/MAPK 信号通路相关基因的致病变异引起的一大类多系统疾病。其中,PPP1CB 基因变异导致毛发松动性无汗型努南综合征样疾病 2(NSLAH2),这是一种罕见疾病,累及神经、心脏、面部和骨骼,并伴有特殊的毛发松动现象。我们报告了一名携带复发性 c.146 C>G(p.Pro49Arg)致病变异的女孩,她表现出经典的 NSLAH 特征,并伴有此前未报道的完全性连合发育不全,这可能扩展了该疾病的表型。Ras 蛋白在少突胶质细胞成熟和分化中的重要作用,可能为我们患者中观察到的髓鞘形成受损提供生物学依据。