ECE2013 Poster Presentations Male reproduction (41 abstracts)
Complete aromatase deficiency in four adult men: detection of a novel mutation and two known mutations in the CYP19A1 gene
Elisa Pignatti 1 , Kursad Unluhizarci 3 , Ermine Kartal 4 , Kamel Ajlouni 5 , Nahla Khawaja 5 , Cesare Carani 1, , Marco Marino 1 , Manuela Simoni 1, , Eleonora Vighi 1 & Vincenzo Rochira 1,
1Chair and Unit of Endocrinology and Metabolism, Department of Biomedical, Metabolic and Neural Sciences, University of Modena and Reggio Emilia, Modena, Italy; 2Integrated Department of Medicine, Endocrinology and Metabolism, Geriatrics, Azienda USL of Modena, NOCSAE of Baggiovara, Modena, Italy; 3Department of Endocrinology, Erciyes University Medical School, Kayseri, Turkey; 4Department of Endocrinology and Metabolisim Disease, Ege University, Ýzmir, Turkey; 5National Center for Diabetes, Endocrinology and Genetics (NCDEG), Amman, Jordan.
Introduction: At present, only eight men with loss-of-function mutations in the CYP19A1 gene have been described. Here we report the genetic study of four adult men with undetectable serum estrogens, unfused epiphyses, eunuchoid skeletal proportions, continuing linear growth, tall stature, genu valgum, osteoporosis, obesity and achantosis nigricans. Patient 1 (26-years/182 cm) and 2 (28-years/187 cm) are from Turkey with a history of consanguinity. Patient 3 (44-years/185 cm) and 4 (29-years/197 cm) are two brothers from Jordan without a history of consanguinity.
Methods: All coding exons with their flanking intronic sequences of CYP19A1 gene, amplified by PCR, were directly sequenced by ABI-Prism 3130 Genetic Analyzer and compared with known human CYP19A1 gene sequences.
Results: Patient 1 was homozygous for a point mutation in the first nucleotide of intron 3 (IVS3+1G>T); Patient 2 homozygous for a G>A mutation (c.1124 G>A) in exon IX resulting in protein missense mutation p.R375H. The two brothers (Patients 3 and 4) had a homozygous mutation in exon IV (c.434 G>A) leading to Arg to Gln substitution at position 115 (p.R115Q). All patients had impaired glucose tolerance, Patient 3 was diabetic, Patient 2 had a history of three forearm bone fractures after minimal trauma, Patient 1, 3, and 4 had impaired liver function and GH secretion.
Conclusions: The description of these new four aromatase-deficient men confirms the detrimental effects of congenital estrogen deficiency on glucose, liver and bone metabolism (particularly bone maturation and mineralization). The homozygous missense mutation in exon IV (p.R115Q) (Patients 3 and 4) is novel. Both aminoacids are basic, but their different conformational structure probably leads to tertiary or quaternary distortion in protein structure. The other two mutations have been previously described in heterozygosis and are found in homozygosis for the first time. Clinical evidence of documented osteoporotic fractures in an aromatase-deficient man is described for the first time.
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Endocrine Abstracts
ISSN 1470-3947 (print) | ISSN 1479-6848 (online)
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