Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism

Background/ObjectivesCongenital hypopituitarism is a raredisease which, for most patients, has no identified molecularcause. We aimed to document the molecular basis of growthretardation in a Moroccan cohort.Design/Patients80 index cases [54 with isolated growth hor-mone deficiency (IGHD), 26 with combined pituitary hormonedeficiency (CPHD)] were screened for molecular defects inGH1(includingLCR-GH1),GHRHR,GHSR,GHRH,PROP1,POU1F1,HESX1,LHX3,LHX4andSOX3.ResultsFive different deleterious mutations were identified in14 patients from eight families. In the IGHD group, three geneswere found to be involved:GH1,GHRHRandGHSR. In theCPHD group,PROP1was the only mutated gene. In addition,two heterozygous variations whose deleterious effect remains tobe demonstrated were identified (inGH1andLHX4), and twopolymorphisms (missense variations) were detected (inLHX3and inGHSR). The prevalence of mutations in this MoroccanGHD cohort was 10% (8/80), 111% (6/54) in the IGHD groupand 77% (2/26) in the CPHD group.ConclusionThis is the first molecular screening of congenitalGHD in a Moroccan population and, like other studies, muta-tions were preferentially identified in familial cases (75%); muta-tions in genes such asPOU1F1,HESX1,SOX3,LHX3andLHX4are extremely rare. The p.R73CPROP1mutation was the mostfrequent mutation in CPHD; this should be the first one toscreen in this population. Our results should contribute to abetter diagnosis and management of this heterogeneous diseaseconditio