Endocrine Abstracts

JOINT379

With the development of genetic screening for disease in childhood, more genetic variants are found. The family segregation study of variants found in disease with autosomal recessive inheritance, may cast doubt on paternity when the father is not a carrier of the variant found in the child. Uniparental isodisomy, which means both alleles originating from a single-parental homologous chromosome, can be associated with pathogenic variants causing autosomal recessive disease and has already been described in other pathologies of chromosome 5 in 10 children (Qian 2021, Park 2019, Gonzalez-Quintana 2020, Numata 2014). We report the case of a child with congenital hypopituitarism. NGS sequencing of a panel of genes identified in PROP1 (Prophet of Pit1) a homozygous variant c. 301_302del resulting in a truncated protein p. Leu102fs, one of the most frequent PROP1 pathogenic variants in Europe. Alterations of PROP1 gene are common findings in children with congenital hypopituitarism and genetic transmission is autosomal recessive. This gene is located on the long arm of chromosome 5 (5q35. 3). The family segregation study found that the mother was a heterozygous carrier of the variant, but the father was not a carrier. We searched for uniparental isodisomy of chromosome 5 in the family by short tandem repeat analysis and SNP-array. Both techniques confirmed that the child has maternal uniparental isodisomy of the entire chromosome 5. Cytogenetic analysis including karyotype and targeted FISH on chromosome 5, performed in proband and parents, showed no alteration of chromosome 5 structure. In conclusion This is the first case report of uniparental isodisomy of chromosome 5 leading to a homozygous mutation of PROP1. Clinicians and genetic counselors should be aware that autosomal recessive disorders due to homozygous variants can occur as a result of uniparental isodisomy, especially if parents are not consanguineous.