MED12 Mutation in Two Families with X-Linked Ohdo Syndrome

Genes

Luigia De Falco¹  Luigi D’Amore¹  Pasquale Savarese¹  Antonio Fico¹  Eloisa Evangelista¹  Raffaella Ruggiero¹  Giovanni Savarese¹  Luca Rocchetti²  Alberto Sensi² 

[1] AMES-Centro Polidiagnostico Strumentale, Srl, 80013 Naples, Italy;U.O. Genetica Medica della Romagna, Dipartimento di Patologia Clinica AUSL, 47522 Cesena, Italy;

关键词: X-linked intellectual deficiency;    next generation sequencing (NGS);    MED12;    genotype-phenotype correlation;   

DOI  :  10.3390/genes12091328

来源: DOAJ

【 摘 要 】

X-linked intellectual deficiency (XLID) is a widely heterogeneous group of genetic disorders that involves more than 100 genes. The mediator of RNA polymerase II subunit 12 (MED12) is involved in the regulation of the majority of RNA polymerase II-dependent genes and has been shown to cause several forms of XLID, including Opitz-Kaveggia syndrome also known as FG syndrome (MIM #305450), Lujan-Fryns syndrome (MIM #309520) and the X-linked Ohdo syndrome (MIM #300895). Here, we report on two first cousins with X-linked Ohdo syndrome with a missense mutation in MED12 gene, identified through whole exome sequencing. The probands had facial features typical of X-linked Ohdo syndrome, including blepharophimosis, ptosis, a round face with a characteristic nose and a narrow mouth. Nextera DNA Exome kit (Illumina Inc., San Diego, CA, USA) was used for exome capture. The variant identified was a c.887G > A substitution in exon 7 of the MED12 gene leading to the substitution of a glutamine for a highly conserved arginine (p. Arg296Gln). Although the variant described has been previously reported in the literature, our study contributes to the expanding phenotypic spectrum of MED12-related disorders and above all, it demonstrates the phenotypic variability among different affected patients despite harboring identical mutations.

【 授权许可】

Unknown