Vol.:(0123456789) 1 3 Molecular Biology Reports https://doi.org/10.1007/s11033-023-08595-y SHORT COMMUNICATION Variants in FREM1 and trisomy 18 identifed in a neonatal progeria patient Saima Siddiqi 1  · Noor ul Ain 1  · Mehran Kauser 1,2  · Zahra Mukhtar 1,3  · Muhammad Ansar 4  · Muhammad Umair 5 Received: 8 March 2023 / Accepted: 14 June 2023 © The Author(s), under exclusive licence to Springer Nature B.V. 2023 Abstract Background Neonatal progeroid disorders are rare disorders with clinical features including low body mass index, proptosis, aged and dysmorphic facial features at the time of birth, prominent veins, sparse scalp hairs, and severe growth retardation. Very few cases have been identifed with an unknown genetic cause. Here, we report clinical and genetic fndings of a proband with hallmark features of neonatal progeria. Methods Microarray comparative genomic hybridization, whole exome sequencing (WES) and Sanger sequencing were performed using standard methods. Results Array combined genome hybridization data revealed trisomy 18 in the proband (II-1), and WES data identifed novel compound heterozygous variants (c.247 C > T; p.H83Y and c.14769868InsA) in the FREM1 gene. Conclusion We report a novel complex case of neonatal progeria with atrial septal defects, trisomy 18 without typical fea- tures of Edward syndrome. The phenotype of the patient was more consistent with neonatal progeria, thus we speculate it to be caused by the FREM1 variants. Keywords FREM1 · Neonatal progeria · Compound heterozygous variants Introduction Progeria is a premature aging disease, and aging is mani- fested at a very early stage in life. It is a rare disease afecting 1 in 4 million newborns worldwide [1]. It is characterized by generalized lipodystrophy, sparse scalp hairs, prominent scalp veins, and failure to thrive [1]. The Hutchinson–Gilford progeria syndrome (HGPS) is the most well characterized form of progeria. HGPS is caused by heterozygous muta- tions in the Lamin A/C (LMNA) gene. LMNA encodes a protein called lamin A which is responsible for determining the shape of the nucleus inside cells. Mutations in LMNA result in defective lamin A protein, which makes the nuclear envelope unstable, damaging the nucleus and causing pre- mature death of cells. However, changes that produce the exact disease phenotype are still unknown. The age of onset of HGPS patients is usually 2 to 3 years, with an average lifespan of 14.6 years [2]. The sign and symptoms of neonatal progeroid patients include pre and post-natal growth retardation, pseudo-hydro- cephalus, severe adipose tissue defciency, old looking face at the time of birth, low birth weight, beak nose and bird head. The average life expectancy of patients with neonatal progeroid disorder is 7 months [3]. The inheritance pattern observed in reported cases suggested a recessive mode of inheritance as parents in all reported cases were normal and usually cousins [4]. The present study describes the clinical and genetic fnd- ings of a novel case of neonatal progeria with atrial sep- tal defects. The patient was diagnosed having a trisomy of * Saima Siddiqi saimasiddiqi2@gmail.com 1 Institute of Biomedical and Genetic Engineering (IBGE), Islamabad, Pakistan 2 Department of Animal Sciences/MLT, Faculty of life sciences, Karakoram International University (KIU), Gilgit, GB, Pakistan 3 PMAS arid Agriculture University, Rawalpindi, Pakistan 4 Laboratory of Genetic medicine and Development, University of Geneva, Geneva, Switzerland 5 Medical Genomics Research Department, King Abdullah International Medical Research Center (KAIMRC), Ministry of National Guard Health Afairs (MNGH), King Saud Bin Abdulaziz University for Health Sciences, Riyadh, Saudi Arabia