{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Pulli K"],"funding":["Academy of Finland","Finnish Cultural Foundation","European Union’s Horizon 2020 research and innovation programme under the Marie Sklodowska-Curie grant agreement","Sigrid Juselius Foundation","Foundation for Pediatric Research","Novo Nordisk Fonden","Biomedicum Helsinki Foundation"],"pagination":["e167598"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC11141940"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(10)"],"pubmed_abstract":["MAPK activating death domain (MADD) is a multifunctional protein regulating small GTPases RAB3 and RAB27, MAPK signaling, and cell survival. Polymorphisms in the MADD locus are associated with glycemic traits, but patients with biallelic variants in MADD manifest a complex syndrome affecting nervous, endocrine, exocrine, and hematological systems. We identified a homozygous splice site variant in MADD in 2 siblings with developmental delay, diabetes, congenital hypogonadotropic hypogonadism, and growth hormone deficiency. This variant led to skipping of exon 30 and in-frame deletion of 36 amino acids. To elucidate how this mutation causes pleiotropic endocrine phenotypes, we generated relevant cellular models with deletion of MADD exon 30 (dex30). We observed reduced numbers of β cells, de"],"journal":["JCI insight"],"pubmed_title":["A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes."],"pmcid":["PMC11141940"],"funding_grant_id":["00200579,00230670","275259","180086,160284","894596","1135","NNF17OC0027448","20210167"],"pubmed_authors":["Ibrahim H","Ahonen P","Vaaralahti K","Tommiska J","Iivonen AP","Vuoristo S","Saarimaki-Vire J","Kansakoski J","Otonkoski T","Raivio T","Liu X","Andoniadou CL","Pulli K","Varjosalo M","Santambrogio A","Kemkem Y","Chandra V","Wang Y"],"additional_accession":[]},"is_claimable":false,"name":"A splice site variant in MADD affects hormone expression in pancreatic β cells and pituitary gonadotropes.","description":"MAPK activating death domain (MADD) is a multifunctional protein regulating small GTPases RAB3 and RAB27, MAPK signaling, and cell survival. Polymorphisms in the MADD locus are associated with glycemic traits, but patients with biallelic variants in MADD manifest a complex syndrome affecting nervous, endocrine, exocrine, and hematological systems. We identified a homozygous splice site variant in MADD in 2 siblings with developmental delay, diabetes, congenital hypogonadotropic hypogonadism, and growth hormone deficiency. This variant led to skipping of exon 30 and in-frame deletion of 36 amino acids. To elucidate how this mutation causes pleiotropic endocrine phenotypes, we generated relevant cellular models with deletion of MADD exon 30 (dex30). We observed reduced numbers of β cells, de","dates":{"release":"2024-01-01T00:00:00Z","publication":"2024 May","modification":"2026-06-01T17:16:10.179Z","creation":"2025-07-25T03:08:06.49Z"},"accession":"S-EPMC11141940","cross_references":{"pubmed":["38775154"],"doi":["10.1172/jci.insight.167598"]}}