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Molecular screening of a large cohort of Moroccan patients with congenital hypopituitarism
Author(s) -
Fritez Nabila,
Sobrier MarieLaure,
Iraqi Hinde,
ViéLuton MariePierre,
Netchine Irène,
El Annas Abdessamad,
Pantel Jacques,
Collot Nathalie,
Rose Sophie,
Piterboth William,
Legendre Marie,
Chraibi Abdelmjid,
Amselem Serge,
Kadiri Abdelkrim,
Hilal Latifa
Publication year - 2015
Publication title -
clinical endocrinology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.055
H-Index - 147
eISSN - 1365-2265
pISSN - 0300-0664
DOI - 10.1111/cen.12706
Subject(s) - ighd , missense mutation , hypopituitarism , cohort , growth hormone deficiency , population , mutation , biology , medicine , genetics , dwarfism , endocrinology , gene , pediatrics , growth hormone , hormone , environmental health
Summary Background/Objectives Congenital hypopituitarism is a rare disease which, for most patients, has no identified molecular cause. We aimed to document the molecular basis of growth retardation in a Moroccan cohort. Design/Patients 80 index cases [54 with isolated growth hormone deficiency ( IGHD ), 26 with combined pituitary hormone deficiency ( CPHD )] were screened for molecular defects in GH 1 (including LCR ‐ GH 1) , GHRHR , GHSR , GHRH , PROP 1 , POU 1F1 , HESX 1 , LHX 3 , LHX 4 and SOX 3 . Results Five different deleterious mutations were identified in 14 patients from eight families. In the IGHD group, three genes were found to be involved: GH 1 , GHRHR and GHSR . In the CPHD group, PROP 1 was the only mutated gene. In addition, two heterozygous variations whose deleterious effect remains to be demonstrated were identified (in GH 1 and LHX 4 ), and two polymorphisms (missense variations) were detected (in LHX 3 and in GHSR ). The prevalence of mutations in this Moroccan GHD cohort was 10% (8/80), 11·1% (6/54) in the IGHD group and 7·7% (2/26) in the CPHD group. Conclusion This is the first molecular screening of congenital GHD in a Moroccan population and, like other studies, mutations were preferentially identified in familial cases (75%); mutations in genes such as POU 1F1 , HESX 1 , SOX 3 , LHX 3 and LHX 4 are extremely rare. The p.R73C PROP 1 mutation was the most frequent mutation in CPHD ; this should be the first one to screen in this population. Our results should contribute to a better diagnosis and management of this heterogeneous disease condition.