Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing
Autor(a) principal: | |
---|---|
Data de Publicação: | 2017 |
Outros Autores: | , , , , , , , , , , , |
Tipo de documento: | Relatório |
Idioma: | eng |
Título da fonte: | Arquivos de Endocrinologia e Metabolismo (Online) |
Texto Completo: | http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972017000600633 |
Resumo: | SUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene. |
id |
SBEM-1_250347718a96ea8d72699ea363079f5e |
---|---|
oai_identifier_str |
oai:scielo:S2359-39972017000600633 |
network_acronym_str |
SBEM-1 |
network_name_str |
Arquivos de Endocrinologia e Metabolismo (Online) |
repository_id_str |
|
spelling |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencingSUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene.Sociedade Brasileira de Endocrinologia e Metabologia2017-12-01info:eu-repo/semantics/reportinfo:eu-repo/semantics/publishedVersiontext/htmlhttp://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972017000600633Archives of Endocrinology and Metabolism v.61 n.6 2017reponame:Arquivos de Endocrinologia e Metabolismo (Online)instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)instacron:SBEM10.1590/2359-3997000000311info:eu-repo/semantics/openAccessCorrea,Fernanda A.França,Marcela M.Fang,QingMa,QianyiBachega,Tania A.Rodrigues,AndresaOzel,Bilge A.Li,Jun Z.Mendonca,Berenice B.Jorge,Alexander A. L.Carvalho,Luciani R.Camper,Sally A.Arnhold,Ivo J. Peng2018-01-31T00:00:00Zoai:scielo:S2359-39972017000600633Revistahttps://www.aem-sbem.com/https://old.scielo.br/oai/scielo-oai.php||aem.editorial.office@endocrino.org.br2359-42922359-3997opendoar:2018-01-31T00:00Arquivos de Endocrinologia e Metabolismo (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM)false |
dc.title.none.fl_str_mv |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
title |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
spellingShingle |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing Correa,Fernanda A. |
title_short |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
title_full |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
title_fullStr |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
title_full_unstemmed |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
title_sort |
Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing |
author |
Correa,Fernanda A. |
author_facet |
Correa,Fernanda A. França,Marcela M. Fang,Qing Ma,Qianyi Bachega,Tania A. Rodrigues,Andresa Ozel,Bilge A. Li,Jun Z. Mendonca,Berenice B. Jorge,Alexander A. L. Carvalho,Luciani R. Camper,Sally A. Arnhold,Ivo J. P |
author_role |
author |
author2 |
França,Marcela M. Fang,Qing Ma,Qianyi Bachega,Tania A. Rodrigues,Andresa Ozel,Bilge A. Li,Jun Z. Mendonca,Berenice B. Jorge,Alexander A. L. Carvalho,Luciani R. Camper,Sally A. Arnhold,Ivo J. P |
author2_role |
author author author author author author author author author author author author |
dc.contributor.author.fl_str_mv |
Correa,Fernanda A. França,Marcela M. Fang,Qing Ma,Qianyi Bachega,Tania A. Rodrigues,Andresa Ozel,Bilge A. Li,Jun Z. Mendonca,Berenice B. Jorge,Alexander A. L. Carvalho,Luciani R. Camper,Sally A. Arnhold,Ivo J. P |
description |
SUMMARY Isolated growth hormone deficiency (IGHD) is the most common pituitary hormone deficiency and, clinically, patients have delayed bone age. High sequence similarity between CYP21A2 gene and CYP21A1P pseudogene poses difficulties for exome sequencing interpretation. A 7.5 year-old boy born to second-degree cousins presented with severe short stature (height SDS −3.7) and bone age of 6 years. Clonidine and combined pituitary stimulation tests revealed GH deficiency. Pituitary MRI was normal. The patient was successfully treated with rGH. Surprisingly, at 10.8 years, his bone age had advanced to 13 years, but physical exam, LH and testosterone levels remained prepubertal. An ACTH stimulation test disclosed a non-classic congenital adrenal hyperplasia due to 21-hydroxylase deficiency explaining the bone age advancement and, therefore, treatment with cortisone acetate was added. The genetic diagnosis of a homozygous mutation in GHRHR (p.Leu144His), a homozygous CYP21A2 mutation (p.Val282Leu) and CYP21A1P pseudogene duplication was established by Sanger sequencing, MLPA and whole-exome sequencing. We report the unusual clinical presentation of a patient born to consanguineous parents with two recessive endocrine diseases: non-classic congenital adrenal hyperplasia modifying the classical GH deficiency phenotype. We used a method of paired read mapping aided by neighbouring mis-matches to overcome the challenges of exome-sequencing in the presence of a pseudogene. |
publishDate |
2017 |
dc.date.none.fl_str_mv |
2017-12-01 |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/report |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
format |
report |
status_str |
publishedVersion |
dc.identifier.uri.fl_str_mv |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972017000600633 |
url |
http://old.scielo.br/scielo.php?script=sci_arttext&pid=S2359-39972017000600633 |
dc.language.iso.fl_str_mv |
eng |
language |
eng |
dc.relation.none.fl_str_mv |
10.1590/2359-3997000000311 |
dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
eu_rights_str_mv |
openAccess |
dc.format.none.fl_str_mv |
text/html |
dc.publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
publisher.none.fl_str_mv |
Sociedade Brasileira de Endocrinologia e Metabologia |
dc.source.none.fl_str_mv |
Archives of Endocrinology and Metabolism v.61 n.6 2017 reponame:Arquivos de Endocrinologia e Metabolismo (Online) instname:Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) instacron:SBEM |
instname_str |
Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
instacron_str |
SBEM |
institution |
SBEM |
reponame_str |
Arquivos de Endocrinologia e Metabolismo (Online) |
collection |
Arquivos de Endocrinologia e Metabolismo (Online) |
repository.name.fl_str_mv |
Arquivos de Endocrinologia e Metabolismo (Online) - Sociedade Brasileira de Endocrinologia e Metabologia (SBEM) |
repository.mail.fl_str_mv |
||aem.editorial.office@endocrino.org.br |
_version_ |
1752122514947964928 |