The abstracts descibes four new cases of patients with aromatase deficiency. Both the clinical features and the results of the molecular studies are reported

CARANI, Cesare

E. Kartal

K. M. Ajlouni

K. Unluhizarci

MARINO, MARCO

N. Khawaja

PIGNATTI, Elisa

ROCHIRA, Vincenzo

SIMONI, Manuela

VIGHI, Eleonora

The study describes 4 new cases of the rare disease aromatase deficienc

K. Ajlouni

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Complete aromatase deficiency in four adult men: detection of a novel mutation and two known mutations in the CYP19A1 gene

24/06/13 23:42COMPLETE AROMATASE DEFICIENCY IN FOUR ADULT MEN: DETECTION OF A…9A1 GENE -- Pignatti et al. 34 (3): FP22-1 -- Endocrine ReviewsPagina 1 di 1http://edrv.endojournals.org/cgi/content/meeting_abstract/34/03_MeetingAbstracts/FP22-1?sid=794652cc-466a-47bc-afd9-ec205a88c1acEndocr Rev, Vol. 34 (03_MeetingAbstracts): FP22-1Copyright © 2013 by The Endocrine SocietyCOMPLETE AROMATASE DEFICIENCY IN FOUR ADULTMEN: DETECTION OF A NOVEL MUTATION AND TWOKNOWN MUTATIONS IN THE CYP19A1 GENEElisa Pignatti1, Kamel Mohammad Ajlouni, MDFACE2, Nahla Khawaja3, KursadUnluhizarci4, Emine Kartal5, Cesare Carani, MD1, Manuela Simoni, MDPhD1, MarcoMarino1, Eleonora Vighi1 and Vincenzo Rochira, MDPhD11 University of Modena & Reggio Emilia, Modena , Italy2 Natl Ctr for Diab Endo and Gen, Amman , Jordan3 National Center for Diabetes, Endocrinology and Genetics (NCDEG), Amman , Jordan4 Faculty of Medicine, Erciyes University, Kayseri , Turkey5 Ege University, zmir , TurkeyINTRODUCTION. At present, only eight men with loss-of-function mutations in theCYP19A1 gene have been described (1). We report the genetic study of four adult menwith undetectable serum estrogens, unfused epiphyses, eunuchoid skeletal proportions,continuing linear growth, tall stature, genu valgum, osteoporosis, obesity and achantosisnigricans. Patient 1 (26-yrs/182cm) and 2 (28-yrs/187cm) are from Turkey, Patient 3 (44-yrs/185cm) and 4 (29-yrs/197cm) are two brothers from Jordan. All patients had a historyof consanguinity (father and mother of each patient are cousins).METHODS. All coding exons with their flanking intronic sequences of CYP19A1 gene,amplified by PCR, were sequenced by ABI-Prism 3130 Genetic Analyzer and comparedwith known human CYP19A1 gene sequences.RESULTS. Patient 1 was homozygous for a point mutation in the first nucleotide of intron3 (IVS3+1G>T); Patient 2 homozygous for a G>A mutation (c.1124 G>A) in exon IXresulting in protein missense mutation p.R375H. The two brothers (Patients 3 and 4) hada homozygous mutation in exon IV (c.434 G>A) leading to Arg to Gln substitution atposition 115 (p.R115Q). All patients had impaired glucose tolerance, Patient 3 wasdiabetic, Patient 2 had a history of three forearm bone fractures after minimal trauma,Patient 1, 3, and 4 had impaired liver function. Patient 1 had documented GH-deficiency,all other patients had no evidence of GH hypersecretion.CONCLUSIONS. The description of these new four aromatase-deficient men confirms thedetrimental effects of congenital estrogen deficiency on glucose, liver and bonemetabolism (particularly bone maturation and mineralization) (1). The homozygousmissense mutation in exon IV (p.R115Q) (Patients 3 and 4) is novel: both aminoacids arebasic, their different conformational structure probably leads to tertiary or quaternarydistortion in protein structure. The other two known mutations are found in homozygosisfor the first time. Clinical evidence of osteoporotic fractures is described for the first timeand further emphasizes estrogen role on bone health in men and the need for fractureprevention in these patients (2). Thus, drugs preventing bone fractures could beconsidered as additional treatment other than estrogen replacement (3). Finally, tallstature with concomitant GH-deficiency or with low to normal GH secretion depends onunfused epiphyses that allows bone elongation resulting in eunuchoid skeletal proportions(4).(1) Rochira V. & Carani C., Nat Rev Endocrinol 2009; 5:559-568. (2) Rochira V. et al.,Bone 2007; 40:1662-1668. (3) Maffei L. et al., J Clin Endocrinol Metab 2004; 89:61-70. (4)Rochira V. et al., J Clin Endocrinol Metab 2010; 95:1626-1633.Nothing to Disclose: EP, KMA, NK, KU, EK, CC, MS, MM, EV, VR*Please take note of The Endocrine Society’s news embargo policy at www.endo-society.org/endo2013/media.cfmHome24/06/13 23:44COMPLETE AROMATASE DEFICIENCY IN FOUR ADULT MEN: DETECTION OF A…1 GENE -- Pignatti et al. 34 (3): SUN-527 -- Endocrine ReviewsPagina 1 di 1http://edrv.endojournals.org/cgi/content/meeting_abstract/34/03_MeetingAbstracts/SUN-527?sid=794652cc-466a-47bc-afd9-ec205a88c1acEndocr Rev, Vol. 34 (03_MeetingAbstracts): SUN-527Copyright © 2013 by The Endocrine SocietyCOMPLETE AROMATASE DEFICIENCY IN FOUR ADULTMEN: DETECTION OF A NOVEL MUTATION AND TWOKNOWN MUTATIONS IN THE CYP19A1 GENEElisa Pignatti1, Kamel Mohammad Ajlouni, MDFACE2, Nahla Khawaja3, KursadUnluhizarci4, Emine Kartal5, Cesare Carani, MD1, Manuela Simoni, MDPhD1, MarcoMarino1, Eleonora Vighi1 and Vincenzo Rochira, MDPhD11 University of Modena & Reggio Emilia, Modena , Italy2 Natl Ctr for Diab Endo and Gen, Amman , Jordan3 National Center for Diabetes, Endocrinology and Genetics (NCDEG), Amman , Jordan4 Faculty of Medicine, Erciyes University, Kayseri , Turkey5 Ege University, zmir , TurkeyINTRODUCTION. At present, only eight men with loss-of-function mutations in theCYP19A1 gene have been described (1). We report the genetic study of four adult menwith undetectable serum estrogens, unfused epiphyses, eunuchoid skeletal proportions,continuing linear growth, tall stature, genu valgum, osteoporosis, obesity and achantosisnigricans. Patient 1 (26-yrs/182cm) and 2 (28-yrs/187cm) are from Turkey, Patient 3 (44-yrs/185cm) and 4 (29-yrs/197cm) are two brothers from Jordan. All patients had a historyof consanguinity (father and mother of each patient are cousins).METHODS. All coding exons with their flanking intronic sequences of CYP19A1 gene,amplified by PCR, were sequenced by ABI-Prism 3130 Genetic Analyzer and comparedwith known human CYP19A1 gene sequences.RESULTS. Patient 1 was homozygous for a point mutation in the first nucleotide of intron3 (IVS3+1G>T); Patient 2 homozygous for a G>A mutation (c.1124 G>A) in exon IXresulting in protein missense mutation p.R375H. The two brothers (Patients 3 and 4) hada homozygous mutation in exon IV (c.434 G>A) leading to Arg to Gln substitution atposition 115 (p.R115Q). All patients had impaired glucose tolerance, Patient 3 wasdiabetic, Patient 2 had a history of three forearm bone fractures after minimal trauma,Patient 1, 3, and 4 had impaired liver function. Patient 1 had documented GH-deficiency,all other patients had no evidence of GH hypersecretion.CONCLUSIONS. The description of these new four aromatase-deficient men confirms thedetrimental effects of congenital estrogen deficiency on glucose, liver and bonemetabolism (particularly bone maturation and mineralization) (1). The homozygousmissense mutation in exon IV (p.R115Q) (Patients 3 and 4) is novel: both aminoacids arebasic, their different conformational structure probably leads to tertiary or quaternarydistortion in protein structure. The other two known mutations are found in homozygosisfor the first time. Clinical evidence of osteoporotic fractures is described for the first timeand further emphasizes estrogen role on bone health in men and the need for fractureprevention in these patients (2). Thus, drugs preventing bone fractures could beconsidered as additional treatment other than estrogen replacement (3). Finally, tallstature with concomitant GH-deficiency or with low to normal GH secretion depends onunfused epiphyses that allows bone elongation resulting in eunuchoid skeletal proportions(4).(1) Rochira V. & Carani C., Nat Rev Endocrinol 2009; 5:559-568. (2) Rochira V. et al.,Bone 2007; 40:1662-1668. (3) Maffei L. et al., J Clin Endocrinol Metab 2004; 89:61-70. (4)Rochira V. et al., J Clin Endocrinol Metab 2010; 95:1626-1633.Nothing to Disclose: EP, KMA, NK, KU, EK, CC, MS, MM, EV, VR*Please take note of The Endocrine Society’s news embargo policy at www.endo-society.org/endo2013/media.cfmHome

The abstract deals with the clinical and genetic description of 4 new cases of aromatase deficiency

Kursad Unluhizarci

Ermine Kartal

Kamel Ajlouni

Nahla Khawaja

Elisa Pignatti

Cesare Carani

Marco Marino

Manuela Simoni

Eleonora Vighi

Vincenzo Rochira

Crossref

Endocrine Abstracts

Complete aromatase deficiency in four adult men: detection of a novel mutation and two known mutations in the<i>CYP19A1</i>gene

Complete aromatase deficiency in four adult men: detection of a novel mutation and two known mutations in the CYP19A1 gene

Abstract

Similar works

Full text

Available Versions

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Archivio istituzionale della ricerca - Università di Modena e Reggio Emilia

Crossref