Prolyl Endopeptidase-like Deficiency Associated with Growth Hormone Deficiency

Abstract

Prolyl endopeptidase-like (PREPL) deficiency (MIM#616224) is a rare congenital disorder characterised by neonatal hypotonia and feeding difficulties, growth hormone (GH) deficiency and hypergonadotropic hypogonadism. This syndrome is an autosomal recessive disease resulting from mutations in the PREPL gene (MIM#609557). Herein we report a 7-year-old female patient with biallelic mutations in PREPL (c.1528C>T in one allele and whole gene deletion in the other) with early growth impairment in infancy. GH deficiency was confirmed at 20 months of life. Recombinant GH treatment was introduced with a good response. Her clinical features were similar to those of previously reported cases. The description of new patients with PREPL deficiency syndrome is essential to better delineate the phenotypic and genotypic spectrum of the disease.

Keywords: Prolyl endopeptidase-like; genetics; growth hormone deficiency.

Figure 1

Growth chart of our patient. The start of somatotropin treatment is indicated (GH), with a subsequent good response GH: growth hormone

Figure 2

Study of the genetic condition. Whole-exome sequencing identified an apparent homozygous variant in PREPL c.1528C>T from paternal inheritance. The array-CGH (with exonic coverage of PREPL) showed a 0.031Mb deletion in 2p21 chromosome (including PREPL gene) inherited from the mother. In the array-CGH, the DNA from the patient is signalled with CY3 red, whereas the DNA from the mother is signalled with CY5 blue PREPL: prolyl endopeptidase-like gene