Long term survival of a patient with Perlman syndrome due to novel compound heterozygous missense mutations in RNB domain of DIS3L2.
Perlman syndrome is a rare overgrowth syndrome characterized by polyhydramnios, macrosomia, distinctive facial appearance, renal dysplasia, and a predisposition to Wilms' tumor. The syndrome is often associated with a high neonatal mortality rate and there are few reports of long-term survivors. We studied a 6-year-old Japanese female patient, who was diagnosed with Perlman syndrome, with novel compound heterozygous mutations in DIS3L2 (c.[367-2A > G];[1328T > A]), who has survived long term. Most reported DIS3L2 mutations have been the homozygous deletion of exon 6 or exon 9, and these mutations would certainly have caused the loss of both RNA binding and degradation activity. We have identified new compound heterozygous mutations in the DIS3L2 of this long-term survivor of Perlman syndrome. The reason our patient has survived long-term would be a missense mutation (c.1328 T > A, p.Met443Lys) having retained RNA binding in both the cold-shock domains and the S1 domain, and through partial RNA degradation. If partial exonuclease functions remain in at least one allele, long-term survival may be possible. Further studies of Perlman syndrome patients with proven DIS3L2 mutations are needed to clarify genotype-phenotype correlation.
Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Noriko
N
Soma
Faculty of Medicine, Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Saga University, Saga, Japan.
Ken
K
Higashimoto
Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Masaru
M
Imamura
Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Akihiko
A
Saitoh
Faculty of Medicine, Division of Molecular Genetics and Epigenetics, Department of Biomolecular Sciences, Saga University, Saga, Japan.
Hidenobu
H
Soejima
Department of Homeostatic Regulation and Development, Graduate School of Medical and Dental Sciences, Niigata University, Niigata, Japan.
Keisuke
K
Nagasaki
D001483:Base Sequence; D002648:Child; D005095:Exoribonucleases / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005320:Fetal Macrosomia / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery; D015870:Gene Expression; D056726:Genetic Association Studies; D006579:Heterozygote; D006801:Humans; D020125:Mutation, Missense; D010375:Pedigree; D000071376:RNA-Binding Motifs; D017741:Survivors; D009396:Wilms Tumor / Q000175:diagnosis / Q000235:genetics* / Q000473:pathology / Q000601:surgery
C571454:DIS3L2 protein, human; D005095:Exoribonucleases
DIS3L2; Perlman syndrome; RNB domain; Wilms’ tumor; compound heterozygous mutations; long-term survivor