Identification of a novel mutation in the polymerase delta 1 (POLD1) gene in a lipodystrophic patient affected by mandibular hypoplasia, deafness, progeroid features (MDPL) syndrome

Definitive diagnosis of mandibular hypoplasia, deafness, progeroid features and lipodystrophy (MDPL) syndrome caused by a recurrent <i>de novo</i> mutation in the <i>POLD1</i> gene

“…The male-to-female ratio is 7:15. Among them, 15 patients had p.Ser605del, including our case; three patients had p.Arg507Cys [11][12][13][14][15][16] and only one had the novel mutation p.Ile1070Ans [16], and two related female patients had the recently identified mutation, p.Glu1067Lys [17]. Thus, the mutation detected in our patient, p.Ser605del, might constitute a hotspot for MDPL syndrome (Table 2, Fig.…”

“…2C). The deletion was reported as a pathogenic variant in patients with mandibular hypoplasia, deafness, progeroid features, and lipodystrophy syndrome (MDPL syndrome) [11][12][13][14][15][16][17]. In addition, no pathogenic mutations were also found in other lipodystrophy-related genes, including FBN1, LIPE, NK, PIK3R1, PSMB8, RTRF, and BANF1, as well as in the Werner helicase gene (WRN) by either Sanger sequencing or WES [21].…”

“…Thus, according to both the unique phenotypic mani- festations and the WES analysis, the patient was diagnosed as having MDPL syndrome; MIM #615381 in the Online Mendelian Inheritance in Man database [11][12][13][14][15][16][17].…”

“…To date, 21 patients with POLD1-related MDPL syndrome [11][12][13][14][15][16][17]26] have been reported in English publications, most frequently from European countries ( Table 2). The male-to-female ratio is 7:15.…”

“…Notably, a new causal factor of progressive lipodystrophy associated with MDPL syndrome has been identified [11][12][13][14][15][16][17]. Mutations in the polymerase delta 1 (POLD1) gene have been detected in several patients with MDPL, suggesting that MDPL is the result of POLD1 gene mutation.…”