Growth hormone deficiency with advanced bone age: phenotypic interaction between GHRH receptor and CYP21A2 mutations diagnosed by sanger and whole exome sequencing
Arch. endocrinol. metab. (Online)
; 61(6): 633-636, Dec. 2017. graf
Article
de En
| LILACS
| ID: biblio-887602
Bibliothèque responsable:
BR1.1
ABSTRACT
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.
Texte intégral:
1
Collection:
01-internacional
Base de données:
LILACS
Sujet principal:
Dysplasies osseuses
/
Steroid 21-hydroxylase
/
Récepteur aux neuropeptides
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Hyperplasie congénitale des surrénales
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Nanisme hypophysaire
Type d'étude:
Diagnostic_studies
/
Etiology_studies
Limites:
Child
/
Humans
/
Infant
/
Male
Langue:
En
Journal:
Arch. endocrinol. metab. (Online)
Sujet du journal:
ENDOCRINOLOGIA
/
METABOLISMO
Année:
2017
Type de document:
Article
Pays d'affiliation:
Brésil