Genetic Screening in Children with Congenital Combined Pituitary Hormone Deficiency

BRASLAVSKY, DÉBORA; SAVEANU, ALEXANDRU; KESELMAN, ANA; BARLIER, ANNE; REYNAUD, RACHEL; PHILIPPON, MELANIE; CASTINETTI, FREDERIC; BRUE, THIERRY; BERGADÁ, IGNACIO

Montevideo

Congreso; XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society; 2012

XXIII Annual Meeting of the Paediatrics Endocrinology Latinoamerican Society

Mutation frequency of genes involved in Congenital multiple pituitary hormone deficiency (CMPHD) varies between populations. Genetic screening in CMPHD from Argentina. In 25 children with sporadic CMPHD genetic studies were guided by phenotypes: hormone deficiencies and MRI findings. Studied genes were PROP1, HESX1, SOX3, PITX2, OTX2, LHX4 and LHX3. Mutations were found in two(8%). Heterozygous LHX4 mutation (p.Lys242del) was found in a boy with corticotroph, somatotroph, thyrotroph and lactotroph deficiencies, pituitary hypoplasia without extrapituitary abnormalities. Heterozygous LHX3 allele variant(p.Arg310Pro) was present in a boy with nystagmus, microcephaly, normal neck rotation; gonadotroph, corticotroph, somatotroph, thyrotroph and lactotroph deficiencies; pituitary hypoplasia, ectopic neurohypophysis and disrupted stalk. LHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of thePROP1, HESX1, SOX3, PITX2, OTX2, LHX4 and LHX3. Mutations were found in two(8%). Heterozygous LHX4 mutation (p.Lys242del) was found in a boy with corticotroph, somatotroph, thyrotroph and lactotroph deficiencies, pituitary hypoplasia without extrapituitary abnormalities. Heterozygous LHX3 allele variant(p.Arg310Pro) was present in a boy with nystagmus, microcephaly, normal neck rotation; gonadotroph, corticotroph, somatotroph, thyrotroph and lactotroph deficiencies; pituitary hypoplasia, ectopic neurohypophysis and disrupted stalk. LHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of theand LHX3. Mutations were found in two(8%). Heterozygous LHX4 mutation (p.Lys242del) was found in a boy with corticotroph, somatotroph, thyrotroph and lactotroph deficiencies, pituitary hypoplasia without extrapituitary abnormalities. Heterozygous LHX3 allele variant(p.Arg310Pro) was present in a boy with nystagmus, microcephaly, normal neck rotation; gonadotroph, corticotroph, somatotroph, thyrotroph and lactotroph deficiencies; pituitary hypoplasia, ectopic neurohypophysis and disrupted stalk. LHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of theLHX4 mutation (p.Lys242del) was found in a boy with corticotroph, somatotroph, thyrotroph and lactotroph deficiencies, pituitary hypoplasia without extrapituitary abnormalities. Heterozygous LHX3 allele variant(p.Arg310Pro) was present in a boy with nystagmus, microcephaly, normal neck rotation; gonadotroph, corticotroph, somatotroph, thyrotroph and lactotroph deficiencies; pituitary hypoplasia, ectopic neurohypophysis and disrupted stalk. LHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of theLHX3 allele variant(p.Arg310Pro) was present in a boy with nystagmus, microcephaly, normal neck rotation; gonadotroph, corticotroph, somatotroph, thyrotroph and lactotroph deficiencies; pituitary hypoplasia, ectopic neurohypophysis and disrupted stalk. LHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of theLHX4 mutation affected a biologically critical and highly conserved residue, in favor of the pathogenic role of the variant in the observed phenotype. Functional studies of the LHX3 mutated protein were suggestive of a rare polymorphism, thus unlikely to account for the phenotype. A genetic screening strategy based on endocrine and neuroradiological phenotype allowed the identification of gene defects. The frequency of mutations in LHX3 based on endocrine and neuroradiological phenotype allowed the identification of gene defects. The frequency of mutations in LHX3 and LHX4 in CMPHD is low. Clinical relevance of such mutations should take into account functional studies and cosegregation pattern. The etiology of most of the cases of CMPHD remains to be established.LHX4 in CMPHD is low. Clinical relevance of such mutations should take into account functional studies and cosegregation pattern. The etiology of most of the cases of CMPHD remains to be established.mutated protein were suggestive of a rare polymorphism, thus unlikely to account for the phenotype. A genetic screening strategy based on endocrine and neuroradiological phenotype allowed the identification of gene defects. The frequency of mutations in LHX3 based on endocrine and neuroradiological phenotype allowed the identification of gene defects. The frequency of mutations in LHX3 and LHX4 in CMPHD is low. Clinical relevance of such mutations should take into account functional studies and cosegregation pattern. The etiology of most of the cases of CMPHD remains to be established.LHX4 in CMPHD is low. Clinical relevance of such mutations should take into account functional studies and cosegregation pattern. The etiology of most of the cases of CMPHD remains to be established.