Atypical presentation in patients with 17 α-hydroxylase deficiency caused by a deletion in the CYP17A1 gene: short stature

Abstract

Background. Patients with 17α-hydroxylase deficiency (17 OHD) usually present with tall stature and eunuchoid features, rather than growth retardation. However, unlike the classic form of the disease, short stature due to a lack of pubertal growth spurt and sex hormone deficiency was present in our four cases. We wanted to emphasize that short stature might be the cause of first presentation in patients with 17 OHD. Cases. We report five patients of Kurdish origin with 17 OHD, four of whom had short stature; two presented because of short stature and two were detected as having short stature. The external genitalia had a female appearance and was prepubertal in all cases. Hypertension was also detected in four of the patients. Serum biochemical and hormonal analyses were performed for each patient. Laboratory data suggesting severe growth hormone (GH) deficiency were obtained from one patient, while the other had a familial history suggesting constitutional delay of growth and puberty (CDGP). Whole exome sequence analysis of the CYP17A1 gene was performed on all patients. STR fragment analysis and multiplex ligation dependent probe amplification (MLPA) analysis was also performed to detect mutations associated with congenital adrenal hyperplasia (CAH) in the CYP17A1 gene. No mutation was detected in the whole exome sequence analysis of the CYP17A1 gene in all five patients, although wide deletions were identified in the 1st-6th exons of this gene at MLPA analysis. Conclusions. Patients with 17α-hydroxylase deficiency can present with short stature because they have no pubertal growth spurt during adolescence. Therefore, 17 OHD should be considered in the differential diagnosis of patients with delayed puberty and short stature.

Identification of a homozygous c.1039C>T (p.R347C) variant in <i>CYP17A1</i> in a 67-year-old female patient with partial 17α-hydroxylase/17,20-lyase deficiency

“…The MLPA method is mainly employed in the molecular diagnosis of CAH owing to 21hydroxylase deficiency for the detection of deletions/ duplications in CYP21A2. There are few studies on the application of MLPA in the diagnosis of 17OHD [12][13][14]. The present case illustrates the need for scrutinizing a homozygous mutation pattern by not only direct DNA sequencing but also MLPA analysis.…”

Presentation, Diagnosis, and Follow-Up Characteristics of 17α-Hydroxylase Deficiency Cases with Exon 1–6 Deletion (Founder Mutation) in the CYP17A1Gene: 20-Year Single-Center Experience

“…The MLPA test is a reliable and convenient method for diagnosing large deletions/duplications and is commonly used when large sets of samples need to be tested in a single run. In different studies conducted in Turkey, it has been reported that exon 1-6 deletion of the CYP17A1 gene may cause a serious phenotypic change by severely disrupting P450c17 enzyme activity, especially in natives from the eastern and southeastern regions of Turkey [Turkkahraman et al, 2015;Kardelen et al, 2018;Bolu et al, 2020;Beştaş et al, 2021]. These results suggest that exon 1-6 deletion is a founder mutation in east and southeast Turkey.…”