Giugliano Teresa, Santoro Claudia, Torella Annalaura, Del Vecchio Blanco Francesca, Bernardo Pia, Nigro Vincenzo, Piluso Giulio
Dipartimento di Biochimica, Biofisica e Patologia Generale, Università degli Studi della Campania "Luigi Vanvitelli,", Naples, Italy.
Dipartimento della Donna, del Bambino e della Chirurgia generale e specialistica, Università degli Studi della Campania "Luigi Vanvitelli,", Naples, Italy.
Am J Med Genet A. 2018 Mar;176(3):722-726. doi: 10.1002/ajmg.a.38589. Epub 2017 Dec 28.
UBE2A deficiency is a syndromic condition of X-linked intellectual disability (ID) characterized by typical dysmorphic features that include synophrys, prominent supraorbital ridges, almond-shaped, and deep-set eyes, large ears, wide mouth, myxedematous appearance, hirsutism, micropenis, and onychodystrophy. To date, only seven familial UBE2A intragenic mutations and nine larger microdeletions encompassing UBE2A have been reported. Here, we describe two siblings with X-linked ID and typical clinical features of UBE2A deficiency caused by a novel hemizygous variant, identified by massively parallel sequencing of X-exome. The synonymous c.330G>A substitution in UBE2A modifies the last nucleotide of exon 5, causing the exon skipping and resulting in an out-of-frame transcript, likely encoding for a truncated form of the ubiquitin-conjugating enzyme E2 A. As confirmed by deep sequencing, the c.330G>A substitution in UBE2A was undetectable in genomic DNA from maternal blood cells, suggesting that the recurrent UBE2A deficiency observed in males of this family is caused by a maternal germline mosaicism.
UBE2A缺乏症是一种X连锁智力障碍（ID）的综合征性疾病，其特征为典型的畸形特征，包括连眉、眶上嵴突出、杏仁状深陷眼、大耳朵、宽嘴巴、黏液性水肿外观、多毛症、小阴茎和甲营养不良。迄今为止，仅报道了7个家族性UBE2A基因内突变和9个包含UBE2A的较大微缺失。在此，我们描述了两名患有X连锁ID且具有UBE2A缺乏症典型临床特征的同胞，该疾病由一种新的半合子变异引起，通过对X外显子组进行大规模平行测序得以鉴定。UBE2A中同义的c.330G>A替换改变了外显子5的最后一个核苷酸，导致外显子跳跃并产生移码转录本，可能编码截短形式的泛素结合酶E2A。深度测序证实，在母亲血细胞的基因组DNA中未检测到UBE2A中的c.330G>A替换，这表明该家族男性中观察到的复发性UBE2A缺乏症是由母系生殖系嵌合体引起的。
