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UBE2A deficiency in two siblings: A novel splicing variant inherited from a maternal germline mosaicism
Author(s) -
Giugliano Teresa,
Santoro Claudia,
Torella Annalaura,
Del Vecchio Blanco Francesca,
Bernardo Pia,
Nigro Vincenzo,
Piluso Giulio
Publication year - 2018
Publication title -
american journal of medical genetics part a
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.064
H-Index - 112
eISSN - 1552-4833
pISSN - 1552-4825
DOI - 10.1002/ajmg.a.38589
Subject(s) - germline , genetics , germline mosaicism , rna splicing , biology , gene , rna
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.