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Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands

  • Malgorzata Kumorowicz-Czoch EMAIL logo , Anna Madetko-Talowska , Adam Dudek and Dorota Tylek-Lemanska
Published/Copyright: January 14, 2015
Journal of Pediatric Endocrinology and Metabolism
From the journal Journal of Pediatric Endocrinology and Metabolism Volume 28 Issue 7-8

Abstract

Background: The morphological and biochemical phenotype of PAX8 mutation in patients with congenital hypothyroidism (CH) is variable. The contribution of mutations in PAX8 gene in children with CH and dysgenetic thyroid glands still remains a subject of interest for researchers.

Patients and methods: Some 48 children (37 girls and 11 boys) with CH associated with thyroid ectopy (n=22), agenesis (n=10), hypoplasia (n=6), or thyroid dysgenesis of unknown cause (n=10) were enrolled. The study participants were born in south-eastern Poland in the years 1993–2012 and were selected for neonatal mass screening for CH. DNA was extracted from peripheral blood samples using Master Pure DNA Purification Kit (Epicentre Biotechnologies, Madison, WI, USA). The 12 exons of the PAX8 gene along with their exon-intron boundaries were amplified and sequenced by the Sanger method. Capillary electrophoresis was run on ABI 3500 (Applied Biosystems, Carlsbad, CA, USA).

Results: Novel heterozygous transition in exon 3 (c.68G>A) was detected in a 3-year-old girl with a thyroid hypoplasia. This substitution was not identified in the patient’s parents (de novo event). Additionally, a novel genetic variant in 3′UTR region of exon 12 (c.*416C>T) occurred in a 3-year-old boy with ectopic thyroid tissue and concomitant congenital urogenital malformation. This heterozygous variant was also detected in other healthy family members. Thirteen well-described single nucleotide polymorphisms were revealed in the PAX8 gene.

Conclusions: The study reports on the occurrence of two novel heterozygous substitutions in the PAX8 gene. Estimation of the contribution of the revealed c.68G>A variant to the etiology of CH in a girl with hypoplastic thyroid requires further functional analysis.

Keywords: congenital hypothyroidism (CH); PAX8 genetic variants; PAX8 mutations; thyroid dysgenesis (TD)
Corresponding author: Malgorzata Kumorowicz-Czoch, MD, PhD, Chair of Pediatrics, Polish-American Institute of Pediatrics, Department of Pediatric and Adolescent Endocrinology, Jagiellonian University Medical College, St. Anna 12 Street, 31-008 Cracow, Poland, Phone: +48 502138120, E-mail:

Acknowledgments

We greatly appreciate the cooperation of all patients and their families. We express our gratitude to Teresa Nizankowska-Blaz, Elzbieta Golebiowska, and Katarzyna Dolezal-Oltarzewska for the referral of patients, to Teresa Ochman and Ewa Samborska for excellent laboratory assistance, and to Ewa Kopytko and Joanna Szydlowska for English proofreading and corrections. We would like to thank our families for supporting us in all aspects.

Conflict of interest statement

Financial support: The study was supported by grant no. N N407 160640 from the National Science Centre.

Disclosure Statement: The authors have nothing to disclose.

References

1. Delange F. Neonatal screening for congenital hypothyroidism: results and perspectives. Horm Res 1997;48:51–61.10.1159/000185485Search in Google Scholar PubMed

2. LaFranchi SH. Approach to the diagnosis and treatment of neonatal hypothyroidism. J Clin Endocrinol Metab 2011;96;10:2959–67.10.1210/jc.2011-1175Search in Google Scholar PubMed

3. De Felice M, Di Lauro R. Thyroid development and its disorders: genetics and molecular mechanism. Endocr Rev 2004;25:722–46.10.1210/er.2003-0028Search in Google Scholar PubMed

4. Park SM, Chatterjee VK. Genetics of congenital hypothyroidism. J Med Genet 2005;42:379–89.10.1136/jmg.2004.024158Search in Google Scholar PubMed PubMed Central

5. Gaudino R, Garel C, Czernichow P, Leger J. Proportion of various types of thyroid disorders among newborns with congenital hypothyroidism and normally located gland: a regional cohort study. Clin Endocrinol 2005;62:444–8.10.1111/j.1365-2265.2005.02239.xSearch in Google Scholar PubMed

6. Castanet M, Polak M, Bonaiti-Pellie C, Lyonnet S, Czernichow P, et al. Nineteen years of national screening for congenital hypothyroidism: familial cases with thyroid dysgenesis suggest the involvement of genetic factors. J Clin Endocrinol Metab 2001;86:2009–14.10.1210/jcem.86.5.7501Search in Google Scholar PubMed

7. Devos H, Rodd C, Gagne N, Laframboise R, van Vliet G. A search for the possible molecular mechanisms of thyroid dysgenesis: sex ratios and associated malformations. J Clin Endocrinol Metab 1999;84:2502–6.10.1210/jcem.84.7.5831Search in Google Scholar PubMed

8. Krude H, Schutz B, Biebermann H, von Moers A, Schnabel D, et al. Choreoathetosis, hypothyroidism, and pulmonary alterations due to human NKX2-1 haploinsufficiency. J Clin Invest 2002;109:475–80.10.1172/JCI0214341Search in Google Scholar

9. Doyle DA, Gonzalez I, Thomas B, Scavina M. Autosomal dominant transmission of congenital hypothyroidism, neonatal respiratory distress, and ataxia caused by a mutation of NKX2-1. J Pediatr 2004;145:190–3.10.1016/j.jpeds.2004.04.011Search in Google Scholar PubMed

10. Moya CM, de Nanclares GP, Castano L, Potau N, Bilbao JR, et al. Functional study of a novel single deletion in the TITF1/NKX2.1 Homeobox gene that produces congenital hypothyroidism and benign chorea but not pulmonary distress. J Clin Endocrinol Metab 2006;91:1832–41.10.1210/jc.2005-1497Search in Google Scholar PubMed

11. Clifton-Bligh RJ, Wentworth JM, Heinz P, Crisp MS, John R, et al. Mutation of the gene encoding human TTF2 associated with thyroid agenesis, cleft palate and choanal atresia. Nat Genet 1998;19:399–401.10.1038/1294Search in Google Scholar PubMed

12. Castanet M, Park SM, Smith A, Bost M, Leger J, et al. A novel loss-of function mutation in TTF-2 is associated with congenital hypothyroidism, thyroid agenesis and cleft palate. Hum Mol Genet 2002;11:2051–9.10.1093/hmg/11.17.2051Search in Google Scholar PubMed

13. Meeus L, Gilbert B, Rydlewski C, Parma J, Lienhardt Roussie A, et al. Characterization of a novel loss of function mutation of PAX8 in a familial case of congenital hypothyroidism with in-place, normal-sized thyroid. J Clin Endocrinol Metab 2004;89:4285–91.10.1210/jc.2004-0166Search in Google Scholar PubMed

14. Trueba SS, Auge J, Mattei G, Etchevers H, Martinovic J, et al. PAX8, TITF1, and FOXE1 gene expression patterns during human development: new insights into human thyroid development and thyroid dysgenesis-associated malformations. J Clin Endocrinol Metab 2005;90:455–62.10.1210/jc.2004-1358Search in Google Scholar PubMed

15. Vilain C, Rydlewski C, Duprez L, Heinrichs C, Abramowicz M, et al. Autosomal dominant transmission of congenital thyroid hypoplasia due to loss-of-function mutation of PAX8. J Clin Endocrinol Metab 2001;86:234–8.10.1210/jc.86.1.234Search in Google Scholar

16. Congdon T, Nguyen LQ, Nogueira CR, Habiby RL, Medeiros-Neto G, et al. A novel mutation (Q40P) in PAX8 associated with congenital hypothyroidism and thyroid hypoplasia: evidence for phenotypic variability in mother and child. J Clin Endocrinol Metab 2001;86:3962–7.10.1210/jcem.86.8.7765Search in Google Scholar PubMed

17. De Sanctis L, Corrias A, Romagnolo D, Di Palma T, Biava A, et al. Familial PAX8 small deletion (c.989_992delACCC) associated with extreme phenotype variability. J Clin Endocrinol Metab 2004;89:5669–74.10.1210/jc.2004-0398Search in Google Scholar PubMed

18. Al Taji E, Biebermann H, Limanova Z, Hnikova O, Zikmund J, et al. Screening for mutations in transcription factors in a Czech cohort of 170 patients with congenital and early-onset hypothyroidism: identification of a novel PAX8 mutation in dominantly inherited early-onset non-autoimmune hypothyroidism. Eur J Endocrinol 2007;156:521–9.10.1530/EJE-06-0709Search in Google Scholar PubMed

19. Narumi S, Muroya K, Asakura Y, Adachi M, Hasegawa T. Transcription factor mutations and congenital hypothyroidism: systematic genetic screening of a population-based cohort of Japanese patients. J Clin Endocrinol Metab 2010;95:1981–5.10.1210/jc.2009-2373Search in Google Scholar PubMed

20. Carvalho A, Hermanns P, Rodrigues AL, Sousa I, Anselmo J, et al. A new PAX8 mutation causing congenital hypothyroidism in three generations of a family is associated with abnormalities in the urogenital tract. Thyroid 2013;23:1074–8.10.1089/thy.2012.0649Search in Google Scholar PubMed

21. Plachov D, Chowdhury K, Walther C, Simon D, Guenet JL, et al. Pax8, a murine paired box gene expressed in the developing excretory system and thyroid gland. Development 1990;110:643–51.10.1242/dev.110.2.643Search in Google Scholar PubMed

22. Esposito C, Miccadei S, Saiardi A, Civitareale D. PAX 8 activates the enhancer of the human thyroperoxidase gene. Biochem J 1998;331:37–40.10.1042/bj3310037Search in Google Scholar PubMed PubMed Central

23. Mascia A, Nitsch L, Di Lauro R, Zannini M. Hormonal control of the transcription factor Pax8 and its role in the regulation of thyroglobulin gene expression in thyroid cells. J Endocrinol 2002;172:163–76.10.1677/joe.0.1720163Search in Google Scholar PubMed

24. Ohno M, Zannini M, Levy O, Carrasco N, Di Lauro R. The paired-domain transcription factor Pax8 binds to the upstream enhancer of the rat sodium/iodide symporter gene and participates in both thyroid specific and cyclic-AMP-dependent transcription. Mol Cell Biol 1999;19:2051–60.10.1128/MCB.19.3.2051Search in Google Scholar PubMed PubMed Central

25. Di Magliano MP, Di Lauro R, Zannini M. Pax8 has a key role in thyroid cell differentiation. PNAS 2000;97:13144–9.10.1073/pnas.240336397Search in Google Scholar PubMed PubMed Central

26. Castanet M, Leenhardt L, Leger J, Simon-Carre A, Lyonnet S, et al. Thyroid hemiagenesis is a rare variant of thyroid dysgenesis with a familial component but without Pax8 mutations in a cohort of 22 cases. Pediatr Res 2005;57:908–13.10.1203/01.PDR.0000161409.04177.36Search in Google Scholar PubMed

27. Cangul H, Morgan NV, Forman JR, Saglam H, Aycan Z, et al. Novel TSHR mutations in consanguineous families with congenital nongoitrous hypothyroidism. Clin Endocrinol 2010;73:671–7.10.1111/j.1365-2265.2010.03849.xSearch in Google Scholar PubMed

28. Ramos HE, Nesi-Franca S, Boldarine VT, Pereira RM, Chiamolera MI, et al. Clinical and molecular analysis of thyroid hypoplasia: a population-based approach in Southern Brazil. Thyroid 2009;19:61–8.10.1089/thy.2008.0116Search in Google Scholar PubMed

29. Macchia PE, Lapi P, Krude H, Pirro MT, Missero C, et al. PAX8 mutations associated with congenital hypothyroidism caused by thyroid dysgenesis. Nat Genet 1998;19:83–6.10.1038/ng0598-83Search in Google Scholar PubMed

30. Di Palma T, Zampella E, Filippone MG, Macchia PE, Ris-Stalpers C, et al. Characterization of a novel loss-of-function mutation of PAX8 associated with congenital hypothyroidism. Clin Endocrinol 2010;73:808–14.10.1111/j.1365-2265.2010.03851.xSearch in Google Scholar PubMed

31. Jo W, Ishizu K, Fujieda K, Tajima T. Congenital hypothyroidism caused by a PAX8 gene mutation manifested as sodium/iodide symporter gene defect. J Thyroid Res. 2010;2010:619013. doi: 10.4061/2010/619013.10.4061/2010/619013Search in Google Scholar PubMed PubMed Central

32. Alcantara-Ortigoza MA, Gonzales-del Angel A, Martinez-Cruz V, Vela-Amieva M, Sanchez-Perez C, et al. Molecular analysis of the PAX8 gene in a sample of Mexican patients with primary congenital hypothyroidism: identification of the recurrent p.Arg31His mutation. Clin Endocrinol 2011;76:147–50.Search in Google Scholar

33. Esperante SA, Rivolta CM, Miravalle L, Herzovich V, Iorcanscky S, et al. Identification and characterization of four PAX8 rare sequence variants (p.T225M, p.L233L, p.G336S and p.A439A) in patients with congenital hypothyroidism and dysgenetic thyroid glands. Clin Endocrinol 2008;68:828–35.10.1111/j.1365-2265.2007.03111.xSearch in Google Scholar PubMed

34. Tonacchera M, Banco ME, Montanelli L, Di Cosmo C, Agretti P, et al. Genetic analysis of the PAX8 gene in children with congenital hypothyroidism and dysgenetic or eutopic thyroid glands: identification of a novel sequence variant. Clin Endocrinol 2007;67:34–40.10.1111/j.1365-2265.2007.02831.xSearch in Google Scholar PubMed

35. Kumorowicz-Czoch M, Tylek-Lemanska D, Starzyk J. Thyroid dysfunctions in children detected in mass screening for congenital hypothyroidism. J Pediatr Endocrinol Metab 2011;24:141–5.10.1515/jpem.2011.080Search in Google Scholar PubMed

36. Madison LD, LaFranchi S. Screening for congenital hypothyroidism: current controversies. Curr Opin Endocrinol Diabetes 2005;12:36–41.10.1097/01.med.0000150854.32675.28Search in Google Scholar

37. Brzewski M, Janczarska D, Jakubowska A, Majkowska Z, Marcinski A, et al. Thyroid volume determined by ultrasound examination in preschool children in Warsaw – reference values and clinical implications. Pol J Radiol 2002;67:41–4.Search in Google Scholar

38. Szybinski Z, Trofimiuk-Muldner M, Buziak-Bereza M, Walczycka L, Hubalewska-Dydejczyk A. Reference values for thyroid volume established by ultrasound in Polish schoolchildren. Pol J Endocrinol 2012;63:104–9.Search in Google Scholar

39. Szinnai G. Genetics of normal and abnormal thyroid development in humans. Best Pract Res Clin Endocrinol Metab 2014;28:133–50.10.1016/j.beem.2013.08.005Search in Google Scholar PubMed

40. Hermanns P, Grasberger H, Cohen R, Freiberg C, Dorr HG, et al. Two cases of thyroid dysgenesis caused by different novel PAX8 mutations in the DNA-binding region: in vitro studies reveal different pathogenic mechanisms. Thyroid 2013;23:791–6.10.1089/thy.2012.0141Search in Google Scholar PubMed PubMed Central

41. Hermanns P, Grasberger H, Refetoff S, Pohlenz J. Mutations in NKX2.5 gene and the PAX8 promoter in a girl with thyroid dysgenesis. J Clin Endocrinol Metab 2011;96:E977–81.10.1210/jc.2010-2341Search in Google Scholar PubMed PubMed Central

42. Lanzerath K, Bettendorf M, Haag C, Kneppo C, Schulze E, et al. Screening for Pax8 mutations in patients with congenital hypothyroidism in South-West Germany. Horm Res 2006;66:96–100.10.1159/000093799Search in Google Scholar PubMed

Supplemental Material

The online version of this article (DOI: 10.1515/jpem-2014-0310) offers supplementary material, available to authorized users.

Received: 2014-7-21
Accepted: 2014-11-14
Published Online: 2015-1-14
Published in Print: 2015-7-1

©2015 by De Gruyter

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
https://doi.org/10.1515/jpem-2014-0310
Keywords for this article
congenital hypothyroidism (CH); PAX8 genetic variants; PAX8 mutations; thyroid dysgenesis (TD)

Articles in the same Issue

  1. Frontmatter
  2. Highlight: Thyroid
  3. Thyroid disorders revisited
  4. Genetic analysis of the paired box transcription factor (PAX8) gene in a cohort of Polish patients with primary congenital hypothyroidism and dysgenetic thyroid glands
  5. Prognostic factors in pediatric differentiated thyroid cancer patients with pulmonary metastases
  6. Reclassification of cytologically atypical thyroid nodules based on radiologic features in pediatric patients
  7. Evaluation of inflammatory and oxidative biomarkers in children with well-controlled congenital hypothyroidism
  8. Investigation of autoimmune diseases accompanying Hashimoto’s thyroiditis in children and adolescents and evaluation of cardiac signs
  9. Neonatal thyroid storm accompanied with severe anaemia
  10. Functional characterization of the novel sequence variant p.S304R in the hinge region of TSHR in a congenital hypothyroidism patients and analogy with other formerly known mutations of this gene portion
  11. Subclinical hypothyroidism as a rare cofactor in chronic kidney disease (CKD) – related anemia
  12. Cytometric analysis of perforin expression in NK cells, CD8+, and CD4+ lymphocytes in children with autoimmune Hashimoto’s thyroiditis – a preliminary study
  13. Papillary thyroid cancer and autoimmune polyglandular syndrome
  14. Review article
  15. Should radioiodine be the first-line treatment for paediatric Graves’ disease?
  16. Image in pediatric endrocrinology
  17. Diffusion-weighted magnetic resonance imaging in a case of severe classic maple syrup urine disease
  18. Original articles
  19. Novel mutations of DAX1 (NR0B1) in two Chinese families with X-linked adrenal hypoplasia congenita and hypogonadotropic hypogonadism
  20. Rickets and vitamin D deficiency in Alaska native children
  21. Persistent elevation of fibroblast growth factor 23 concentrations in healthy appropriate-for-gestational-age preterm infants
  22. Parents’ experiences of having a baby with ambiguous genitalia
  23. Effect of GnRHa 3.75 mg subcutaneously every 6 weeks on adult height in girls with idiopathic central precocious puberty
  24. Congenital adrenal hyperplasia in children – a survey on the current practice in the UK
  25. Randomized clinical trial evaluating metformin versus oral contraceptive pills in the treatment of adolescents with polycystic ovarian syndrome
  26. Influence of the body weight on the onset and progression of puberty in boys
  27. Therapy monitoring in congenital adrenal hyperplasia by dried blood samples
  28. Hyperinsulinemic hypoglycemia: think of hyperinsulinism/hyperammonemia (HI/HA) syndrome caused by mutations in the GLUD1 gene
  29. Sulfonylurea in the treatment of neonatal diabetes mellitus children with heterogeneous genetic backgrounds
  30. Monitoring gonadotropin-releasing hormone analogue (GnRHa) treatment in girls with central precocious puberty: a comparison of four methods
  31. Dietary intake, body composition, and physical activity among young patients with type 1 diabetes mellitus
  32. Metabolic syndrome in obese children and adolescents in Serbia: prevalence and risk factors
  33. Progressive osseous heteroplasia, as an isolated entity or overlapping with Albright hereditary osteodystrophy
  34. Patient reports
  35. 17α-Hydroylase/17,20-lyase deficiency related to P.Y27*(c.81C>A) mutation in CYP17A1 gene
  36. A patient developing anaphylaxis and sensitivity to two different GnRH analogues and a review of literature
  37. Idiopathic short stature due to novel heterozygous mutation of the aggrecan gene
  38. Triple A syndrome with a novel indel mutation in the AAAS gene and delayed puberty
  39. Case report: long-term follow-up of a 45,X male with SHOX haploinsufficiency
  40. Antenatal Bartter syndrome presenting as hyperparathyroidism with hypercalcemia and hypercalciuria: a case report and review
  41. Successful use of continuous subcutaneous hydrocortisone infusion after bilateral adrenalectomy secondary to bilateral pheochromocytoma
  42. Donohue syndrome: a new case with a new complication
  43. Euprolactinemic galactorrhea secondary to domperidone treatment
  44. 17βHSD-3 enzyme deficiency due to novel mutations in the HSD17B3 gene diagnosed in a neonate
  45. Two different patterns of mini-puberty in two 46,XY newborns with 17β-hydroxysteroid dehydrogenase type 3 deficiency
  46. Short communication
  47. Early onset hearing loss in autosomal recessive hypophosphatemic rickets caused by loss of function mutation in ENPP1
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