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A novel 9 bp deletion (c.1271_1279delGTGCCCGCG) in exon 10 of CYP21A2 gene causing severe congenital adrenal hyperplasia
Ist Teil von
Endocrine, 2021-07, Vol.73 (1), p.196-202
Ort / Verlag
New York: Springer US
Erscheinungsjahr
2021
Quelle
SpringerLink (Online service)
Beschreibungen/Notizen
Background
Congenital adrenal hyperplasia (CAH) is an autosomal recessive disorder of adrenal steroidogenesis with a broad spectrum of clinical presentations, ranging from the severe classical salt-wasting (SW) and simple-virilizing (SV) form, to the mild nonclassical form. A large variety of
CYP21A2
genotypes in correlation with phenotype have been described.
Materials and methods
DNA samples from a 14-day-old male newborn with clinical and laboratory signs of SW CAH and family members were subjected for molecular analysis of the nine most common point
CYP21A2
mutations by ACRS/PCR method. Direct DNA sequencing of the whole
CYP21A2
gene was performed to detect the second mutant allele in the patient. The in silico predicting analysis and the crystal structure analysis of the mutated CYP21A2 protein have been performed.
Results
Molecular analysis confirmed that the patient was compound heterozygote carrying p.Q318X mutation inherited from the mother and a novel c.1271_1279delGTGCCCGCG (p.G424_R426del) variant in exon 10 inherited from the father. The in silico predicting software tools classified the novel mutation as pathogenic. Crystal structure analysis showed that the three residues affected by the novel in-frame deletion form several hydrogen bonds that could lead to impaired stability and function of the CYP21A2 protein. These findings were concordant with the patient’s phenotype. The need of several molecular methods to elucidate the genotype in this patient has also been discussed.
Conclusions
A novel 9 bp deletion in
CYP21A2
gene with predicted pathogenic effect on the enzyme activity was detected in neonatal patient causing severe SW CAH.