Börjeson-Forssman-Lehman Syndrome (BFLS) is a rare X-linked recessive syndrome characterized by intellectual disability, developmental delay, obesity, epilepsy, swelling of the subcutaneous tissues of the face, large but not deformed ears, hypogonadism, and gynecomastia. Pathogenic mutations in PHD finger protein 6 (PHF6) have been reported to cause BFLS. In this study, we describe two male siblings with mild intellectual disability, global developmental delay, short stature, microcephaly, and nyctalopia. Whole exome sequencing of the affected siblings and the parents identified a missense variant (c.413C > G) in the PHF6 gene, which leads to alteration of a serine residue at position 138 to cysteine. This mutation is located in a highly conserved region. Sanger sequencing confirmed the segregation of this mutation in the family in an X-linked recessive fashion. Multiple mass spectrometry-based proteomic studies have reported phosphorylation at serine 138 that describes the possible role of serine 138 in signaling. This novel variant in PHF6 gene helped in establishing a diagnosis of BFLS.

中文翻译：

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导致Börjeson-Forssman-Lehman综合征的PHF6基因的新型错义变异。

Börjeson-Forssman-Lehman综合征（BFLS）是一种罕见的X连锁隐性综合征，其特征在于智力残疾，发育迟缓，肥胖，癫痫，面部皮下组织肿胀，大而不会变形的耳朵，性腺功能减退和男性乳房发育不全。据报道，PHD手指蛋白6（PHF6）的致病性突变可导致BFLS。在这项研究中，我们描述了两个患有轻度智力障碍，整体发育迟缓，身材矮小，小头畸形和夜视的男性兄弟姐妹。受影响的兄弟姐妹的整个外显子测序和在所识别的错义变异体（c.413C> G）父母PHF6基因，导致第138位的丝氨酸残基变为半胱氨酸。该突变位于高度保守的区域。桑格测序证实该突变以X连锁隐性方式在家族中分离。基于多个质谱的蛋白质组学研究已经报道了丝氨酸138的磷酸化，描述了丝氨酸138在信号传导中的可能作用。PHF6基因中的这个新变异有助于诊断BFLS。