A Genetic Approach in the Evaluation of Short Stature

DÖNMEZ, AYŞE SENA; turkyilmaz, ayberk; Cayir, Atilla

doi:10.5152/eurasianjmed.2022.22171

A Genetic Approach in the Evaluation of Short Stature

Ayberk TÜRKYILMAZ, (Karadeniz Teknik Üniversitesi, Tıp Fakültesi, Tıbbi Genetik Anabilim Dalı, Trabzon, Türkiye)

AYŞE SENA DÖNMEZ, (Bölgesel Eğitim ve Araştırma Hastanesi, Pediatri Bölümü, Erzurum, Türkiye)

Atilla ÇAYIR (Bölge Eğitim ve Araştırma Hastanesi, Çocuk Endokrinolojisi Anabilim Dalı, Erzurum, Türkiye)

Eurasian Journal of Medicine

4 0

Yıl: 2022 Cilt: 54 Sayı: 1 Sayfa Aralığı: 179 - 186 Metin Dili: İngilizce DOI: 10.5152/eurasianjmed.2022.22171 İndeks Tarihi: 24-05-2023

A Genetic Approach in the Evaluation of Short Stature

Öz:

Short stature is considered a condition in which the height is 2 standard deviations below the mean height of a given age, sex, and population group. Human height is a polygenic and heterogeneous characteristic, and its heritability is reported to be approximately 80%. More than 600 variants associated with human growth were detected in the genome-wide association studies. Rare and common variants concurrently affect human height. The rare variations that play a role in human height determination and have a strong impact on protein functions lead to monogenic short stature phenotypes, which are a highly heterogeneous group. With rapidly developing technologies in the last decade, molecular genetic tests have begun to be used widely in clinical genetics, and thus, the genetic etiology of several rare diseases has been elucidated. Identifying the genetic etiology underlying idiopathic short stature which represents phenotypically heterogeneous group of diseases ranging from isolated short stature to severe and syndromic short stature has promoted the understanding of the genetic regulation of growth plate and longitudinal bone growth. In cases of short stature, definite molecular diagnosis based on genetic evaluation enables the patient and family to receive genetic counseling on the natural course of the disease, prognosis, genetic basis, and recurrence risk. The determination of the genetic etiology in growth disorders is essential for the development of novel targeted therapies and crucial in the development of mutation-specific treatments in the future.

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Belge Türü: Makale Makale Türü: Derleme Erişim Türü: Erişime Açık

1. Cohen P, Rogol AD, Deal CL, et al. Consensus statement on the diagnosis and treatment of children with idiopathic short stature: a summary of the Growth Hormone Research Society, the Lawson Wilkins Pediatric Endocrine Society, and the European Society for Paediatric Endocrinology Workshop. J Clin Endocrinol Metab. 2008;93(11):4210-4217. [CrossRef]
2. Bhadada SK, Agrawal NK, Singh SK, Agrawal JK. Etiological profile of short stature. Indian J Pediatr. 2003;70(7):545-547. [CrossRef]
3. Savage MO, Backeljauw PF, Calzada R, et al. Early detection, referral, investigation, and diagnosis of children with growth disorders. Horm Res Paediatr. 2016;85(5):325-332. [CrossRef]
4. Velayutham K, Selvan SSA, Jeyabalaji RV, Balaji S. Prevalence and etiological profile of short stature among school children in a south Indian population. Indian J Endocrinol Metab. 2017;21(6):820-822. [CrossRef]
5. Ruo-Qian C, Shui-Xian S, Yue-Zhen T, et al. A cluster systematic sampling survey of the body height distribution profile and the prevalence of short stature of urban and surburban children aged from 6 to 18 years in Shanghai. Chin J Evid Based Pediatr. 2009;4(1):5.
6. Lindsay R, Feldkamp M, Harris D, Robertson J, Rallison M. Utah Growth Study: growth standards and the prevalence of growth hormone deficiency. J Pediatr. 1994;125(1):29-35. [CrossRef]
7. Voss LD, Mulligan J, Betts PR, Wilkin TJ. Poor growth in school entrants as an index of organic disease: the Wessex growth study. Br Med J. 1992;305(6866):1400-1402. [CrossRef]
8. Ece A, Ceylan A, Dikici B, Bilici M, Davutoğlu M. The prevalence of short stature, underweight and obesity in schoolchildren in Diyarbakir, Turkey. Van. Med J. 2004;11(4):128-136.
9. Genç Kayıran P, Taymaz T, Kayıran SM, Memioğlu N, Taymaz B, Gürakan B. The frequency of overweight, obesity and short stature among primary school students in three different regions of Turkey. The Medical Bulletin of Sisli Etfal Hospital. 2011;45(1):13-18.
10. İnanç BB. Short stature and low weight in schoolchildren. J Clin Anal Med. 2015;6(5):545-549.
11. Visscher PM, Medland SE, Ferreira MAR, et al. Assumption-free estimation of heritability from genome-wide identity-by-descent sharing between full siblings. PLOS Genet. 2006;2(3):e41. [CrossRef]
12. Lango Allen H, Estrada K, Lettre G, et al. Hundreds of variants clustered in genomic loci and biological pathways affect human height. Nature. 2010;467(7317):832-838. [CrossRef]
13. Silventoinen K, Sammalisto S, Perola M, et al. Heritability of adult body height: a comparative study of twin cohorts in eight countries. Twin Res. 2003;6(5):399-408. [CrossRef]
14. Marouli E, Graff M, Medina-Gomez C, et al. Rare and low-frequency coding variants alter human adult height. Nature. 2017;542(7640):186-190. [CrossRef]
15. Wood AR, Esko T, Yang J, et al. Defining the role of common variation in the genomic and biological architecture of adult human height. Nat Genet. 2014;46(11):1173-1186. [CrossRef]
16. Lui JC, Nilsson O, Chan Y, et al. Synthesizing genome-wide association studies and expression microarray reveals novel genes that act in the human growth plate to modulate height. Hum Mol Genet. 2012;21(23):5193-5201. [CrossRef]
17. Gahl WA, Markello TC, Toro C, et al. The National Institutes of Health undiagnosed diseases program: insights into rare diseases. Genet Med. 2012;14(1):51-59. [CrossRef]
18. Ahn J, Oh J, Suh J, et al. Next-generation sequencing-based mutational analysis of idiopathic short stature and isolated growth hormone deficiency in Korean pediatric patients. Mol Cell Endocrinol. 2022;544:111489. [CrossRef]
19. Jee YH, Andrade AC, Baron J, Nilsson O. Genetics of short stature. Endocrinol Metab Clin North Am. 2017;46(2):259-281. [CrossRef]
20. Alatzoglou KS, Webb EA, Le Tissier P, Dattani MT. Isolated growth hormone deficiency (GHD) in childhood and adolescence: recent advances. Endocr Rev. 2014;35(3):376-432. [CrossRef]
21. Laron Z. Lessons from 50 years of study of Laron syndrome. Endocr Pract. 2015;21(12):1395- 1402. [CrossRef]
22. Ross RJ. The GH receptor and GH insensitivity. Growth Horm IGF Res. 1999;9(suppl B):42-5. [CrossRef]
23. Bernasconi A, Marino R, Ribas A, et al. Characterization of immunodeficiency in a patient with growth hormone insensitivity secondary to a novel STAT5b gene mutation. Pediatrics. 2006;118(5):e1584-e1592. [CrossRef]
24. Fuqua JS, Derr M, Rosenfeld RG, Hwa V. Identification of a novel heterozygous IGF1 splicing mutation in a large kindred with familial short stature. Horm Res Paediatr. 2012;78(1):59-66. [CrossRef]
25. Abou Ghoch J, Choucair N, Pfäffle R, Mégarbané A. Homozygous mutation of the IGF1 receptor gene in a patient with severe pre-and postnatal growth failure and congenital malformations. Eur J Endocrinol. 2013;168:K1-K7.
26. Kansra AR, Dolan LM, Martin LJ, Deka R, Chernausek SD. IGF receptor gene variants in normal adolescents: effect on stature. Eur J Endocrinol. 2012;167(6):777-781. [CrossRef]
27. Kronenberg HM. Developmental regulation of the growth plate. Nature. 2003;423(6937):332- 336. [CrossRef]
28. Bonaventure J, Rousseau F, Legeai Mallet L, Le Merrer ML, Munnich A, Maroteaux P. Common mutations in the gene encoding fibroblast growth factor receptor 3 account for achondroplasia, hypochondroplasia and thanatophoric dysplasia. Acta Paediatr Suppl. 1996;417:33-38. [CrossRef]
29. Foldynova Trantirkova S, Wilcox WR, Krejci P. Sixteen years and counting: the current understanding of fibroblast growth factor receptor 3 (FGFR3) signaling in skeletal dysplasias. Hum Mutat. 2012;33(1):29-41. [CrossRef]
30. Rousseau F, Bonaventure J, Legeai-Mallet L, et al. Mutations in the gene encoding fibroblast growth factor receptor-3 in achondroplasia. Nature. 1994;371(6494):252-254. [CrossRef]
31. Wang J, Wang Z, An Y, et al. Exome sequencing reveals a novel PTHLH mutation in a Chinese pedigree with brachydactyly type E and short stature. Clin Chim Acta. 2015;446:9-14. [CrossRef]
32. Martin TJ, Gillespie MT. Of mice and men, recapitulation of Blomstrand’s chondrodysplasia. J Clin Endocrinol Metab. 2001;86(4):1487-1488. [CrossRef]
33. Schipani E, Kruse K, Jüppner H. A constitutively active mutant PTH-PTHrP receptor in Jansentype metaphyseal chondrodysplasia. Science. 1995;268(5207):98-100. [CrossRef]
34. Hellemans J, Coucke PJ, Giedion A, et al. Homozygous mutations in IHH cause acrocapitofemoral dysplasia, an autosomal recessive disorder with cone-shaped epiphyses in hands and hips. Am J Hum Genet. 2003;72(4):1040-1046. [CrossRef]
35. Lehmann K, Seemann P, Stricker S, et al. Mutations in bone morphogenetic protein receptor 1B cause brachydactyly type A2. Proc Natl Acad Sci U S A. 2003;100(21):12277-12282. [CrossRef]
36. Oishi I, Suzuki H, Onishi N, et al. The receptor tyrosine kinase Ror2 is involved in non canonical Wnt5a/JNK signalling pathway. Genes Cells. 2003;8(7):645-654. [CrossRef]
37. Afzal AR, Rajab A, Fenske CD, et al. Recessive Robinow syndrome, allelic to dominant brachydactyly type B, is caused by mutation of ROR2. Nat Genet. 2000;25(4):419-422. [CrossRef]
38. Olney RC, Bükülmez Hl, Bartels CF, et al. Heterozygous mutations in natriuretic peptide receptor-B (NPR2) are associated with short stature. J Clin Endocrinol Metabol. 2006;91(4):1229-1232.
39. Begemann M, Zirn B, Santen G, et al. Paternally inherited IGF2 mutation and growth restriction. N Engl J Med. 2015;373(4):349-356. [CrossRef]
40. Giabicani E, Netchine I, Brioude F. New clinical and molecular insights into Silver–Russell syndrome. Curr Opin Pediatr. 2016;28(4):529-535. [CrossRef]
41. Dierker T, Bachvarova V, Krause Y, et al. Altered heparan sulfate structure in Glce−/− mice leads to increased Hedgehog signaling in endochondral bones. Matrix Biol. 2016;49:82-92. [CrossRef]
42. Terhal PA, Nievelstein RJA, Verver EJ, et al. A study of the clinical and radiological features in a cohort of 93 patients with a COL2A1 mutation causing spondyloepiphyseal dysplasia congenita or a related phenotype. Am J Med Genet A. 2015;167A(3):461-475. [CrossRef]
43. Tompson SW, Bacino CA, Safina NP, et al. Fibrochondrogenesis results from mutations in the COL11A1 type XI collagen gene. Am J Hum Genet. 2010;87(5):708-712. [CrossRef]
44. Bonaventure J, Chaminade F, Maroteaux P. Mutations in three subdomains of the carboxy-terminal region of collagen type X account for most of the Schmid metaphyseal dysplasias. Hum Genet. 1995;96(1):58-64. [CrossRef]
45. Unger S, Bonafé L, Superti-Furga A. Multiple epiphyseal dysplasia: clinical and radiographic features, differential diagnosis and molecular basis. Best Pract Res Clin Rheumatol. 2008;22(1):19-32. [CrossRef]
46. Gleghorn L, Ramesar R, Beighton P, Wallis G. A mutation in the variable repeat region of the aggrecan gene (AGC1) causes a form of spondyloepiphyseal dysplasia associated with severe, premature osteoarthritis. Am J Hum Genet. 2005;77(3):484-490. [CrossRef]
47. Briggs MD, Hoffman SM, King LM, et al. Pseudoachondroplasia and multiple epiphyseal dysplasia due to mutations in the cartilage oligomeric matrix protein gene. Nat Genet. 1995;10(3):330- 336. [CrossRef]
48. Chapman KL, Mortier GR, Chapman K, Loughlin J, Grant ME, Briggs MD. Mutations in the region encoding the von Willebrand factor A domain of matrilin-3 are associated with multiple epiphyseal dysplasia. Nat Genet. 2001;28(4):393- 396. [CrossRef]
49. Cain SA, McGovern A, Baldwin AK, Baldock C, Kielty CM. Fibrillin-1 mutations causing Weill- Marchesani syndrome and acromicric and geleophysic dysplasias disrupt heparan sulfate interactions. PLOS ONE. 2012;7(11):e48634. [CrossRef]
50. Nicole S, Davoine CS, Topaloglu H, et al. Perlecan, the major proteoglycan of basement membranes, is altered in patients with Schwartz-Jampel syndrome (chondrodystrophic myotonia). Nat Genet. 2000;26(4):480-483. [CrossRef]
51. Jakubiczka S, Bettecken T, Koch G, Tüysüz B, Wollnik B, Wieacker P. Campomelic dysplasia without sex reversal in a Turkish patient is due to mutation Ala119Val within the SOX9 gene. Clin Dysmorphol. 2001;10(3):197-201. [CrossRef]
52. Binder G. Short stature due to SHOX deficiency: genotype, phenotype, and therapy. Horm Res Paediatr. 2011;75(2):81-89. [CrossRef]
53. Alazami AM, Al Owain M, Alzahrani F, et al. Loss of function mutation in LARP7, chaperone of 7SK ncRNA, causes a syndrome of facial dysmorphism, intellectual disability, and primordial dwarfism. Hum Mutat. 2012;33(10):1429- 1434. [CrossRef]
54. Sirmaci A, Spiliopoulos M, Brancati F, et al. Mutations in ANKRD11 cause KBG syndrome, characterized by intellectual disability, skeletal malformations, and macrodontia. Am J Hum Genet. 2011;89(2):289-294. [CrossRef]
55. Roelfsema JH, Peters DJ. Rubinstein–Taybi syndrome: clinical and molecular overview. Expert Rev Mol Med. 2007;9(23):1-16. [CrossRef]
56. Bögershausen N, Gatinois V, Riehmer V, et al. Mutation update for Kabuki syndrome genes KMT2D and KDM6A and further delineation of X linked Kabuki syndrome subtype 2. Hum Mutat. 2016;37(9):847-864. [CrossRef]
57. Mokrani Benhelli H, Gaillard L, Biasutto P, et al. Primary microcephaly, impaired DNA replication, and genomic instability caused by compound heterozygous ATR mutations. Hum Mutat. 2013;34(2):374-384. [CrossRef]
58. Ogi T, Walker S, Stiff T, et al. Identification of the first ATRIP–deficient patient and novel mutations in ATR define a clinical spectrum for ATR– ATRIP Seckel syndrome. PLOS Genet. 2012;8(11):e1002945. [CrossRef]
59. Qvist P, Huertas P, Jimeno S, et al. CtIP mutations cause Seckel and Jawad syndromes. PLOS Genet. 2011;7(10):e1002310. [CrossRef]
60. Harley ME, Murina O, Leitch A, et al. TRAIP promotes DNA damage response during genome replication and is mutated in primordial dwarfism. Nat Genet. 2016;48(1):36-43. [CrossRef]
61. Pastorczak A, Szczepanski T, Mlynarski W, International Berli n-Fra nkfur t-Mun ster (I-BFM) ALL host genetic variation working group. Clinical course and therapeutic implications for lymphoid malignancies in Nijmegen breakage syndrome. Eur J Med Genet. 2016;59(3):126-132. [CrossRef]
62. Boerkoel CF, O'neill S, André JL, et al. Manifestations and treatment of Schimke immuno-osseous dysplasia: 14 new cases and a review of the literature. Eur J Pediatr. 2000;159(1-2):1-7. [CrossRef]
63. Ben Omran TI, Cerosaletti K, Concannon P, Weitzman S, Nezarati MM. A patient with mutations in DNA ligase IV: clinical features and overlap with Nijmegen breakage syndrome. Am J Med Genet A. 2005;137A(3):283-287. [CrossRef]
64. Rosin N, Elcioglu NH, Beleggia F, et al. Mutations in XRCC4 cause primary microcephaly, short stature and increased genomic instability. Hum Mol Genet. 2015;24(13):3708-3717. [CrossRef]
65. Rauen KA. The rasopathies. Annu Rev Genomics Hum Genet. 2013;14:355-369. [CrossRef]
66. Tidyman WE, Rauen KA. Pathogenetics of the RASopathies. Hum Mol Genet. 2016;25(R2):R123- R132. [CrossRef]
67. Aoki Y, Niihori T, Inoue S-i, Matsubara Y. Recent advances in RASopathies. J Hum Genet. 2016;61(1):33-39. [CrossRef]
68. Pasteris NG, Cadle A, Logie LJ, et al. Isolation and characterization of the faciogenital dysplasia (Aarskog-Scott syndrome) gene: a putative RhoRac guanine nucleotide exchange factor. Cell. 1994;79(4):669-678. [CrossRef]
69. Ahrens W, Hiort O, Staedt P, Kirschner T, Marschke C, Kruse K. Analysis of the GNAS1 gene in Albright’s hereditary osteodystrophy. J Clin Endocrinol Metab. 2001;86(10):4630-4634. [CrossRef]
70. Chudasama KK, Winnay J, Johansson S, et al. SHORT syndrome with partial lipodystrophy due to impaired phosphatidylinositol 3 kinase signaling. Am J Hum Genet. 2013;93(1):150-157. [CrossRef]
71. Flechtner I, Lambot-Juhan K, Teissier R, et al. Unexpected high frequency of skeletal dysplasia in idiopathic short stature and small for gestational age patients. Eur J Endocrinol. 2014;170(5):677-684. [CrossRef]
72. Gkourogianni A, Andrew M, Tyzinski L, et al. Clinical characterization of patients with autosomal dominant short stature due to aggrecan mutations. J Clin Endocrinol Metab. 2017;102(2):460-469. [CrossRef]
73. Geffner M, Lundberg M, Koltowska- Häggström M, et al. Changes in height, weight, and body mass index in children with craniopharyngioma after three years of growth hormone therapy: analysis of KIGS (Pfizer International Growth Database). J Clin Endocrinol Metab. 2004;89(11):5435-5440. [CrossRef]
74. Hirschfeldova K, Solc R, Baxova A, et al. SHOX gene defects and selected dysmorphic signs in patients of idiopathic short stature and Léri– Weill dyschondrosteosis. Gene. 2012;491(2):123- 127. [CrossRef]
75. Huber C, Rosilio M, Munnich A, Cormier- Daire V, French SHOX GeNeSIS Module. High incidence of SHOX anomalies in individuals with short stature. J Med Genet. 2006;43(9):735-739. [CrossRef]
76. Jorge AA, Souza SC, Nishi MY, et al. SHOX mutations in idiopathic short stature and Leri Weill dyschondrosteosis: frequency and phenotypic variability. Clin Endocrinol (Oxf ). 2007;66(1):130-135. [CrossRef]
77. Sandoval GT, Jaimes GC, Barrios MC, Cespedes C, Velasco HM. SHOX gene and conserved noncoding element deletions/duplications in C olombian patients with idiopathic short stature. Mol Genet Genomic Med. 2014;2(2):95- 102. [CrossRef]
78. Binder G, Renz A, Martinez A, et al. SHOX haploinsufficiency and Leri-Weill dyschondrosteosis: prevalence and growth failure in relation to mutation, sex, and degree of wrist deformity. J Clin Endocrinol Metab. 2004;89(9):4403-4408. [CrossRef]
79. Gravholt CH, Andersen NH, Conway GS, et al. Clinical practice guidelines for the care of girls and women with Turner syndrome: proceedings from the 2016 Cincinnati International Turner Syndrome Meeting. Proceedings From 2016 Cincinnati International Turner Syndrome Meeting. Eur J Endocrinol. 2017;177(3):G1-G70. [CrossRef]
80. Mintz CS, Seaver LH, Irons M, Grimberg A, Lozano R, ACMG Professional Practice and Guidelines Committee. Focused Revision: ACMG practice resource: genetic evaluation of short stature. Genet Med. 2021;23(5):813-815. [CrossRef]
81. Van Duyvenvoorde HA, Lui JC, Kant SG, et al. Copy number variants in patients with short stature. Eur J Hum Genet. 2014;22(5):602-609. [CrossRef]
82. Zahnleiter D, Uebe S, Ekici AB, et al. Rare copy number variants are a common cause of short stature. PLOS Genet. 2013;9(3):e1003365. [CrossRef]
83. Canton AP, Costa SS, Rodrigues TC, et al. Genome-wide screening of copy number variants in children born small for gestational age reveals several candidate genes involved in growth pathways. Eur J Endocrinol. 2014;171(2):253-262. [CrossRef]
84. Wit JM, Van Duyvenvoorde HA, Van Klinken JB, et al. Copy number variants in short children born small for gestational age. Horm Res Paediatr. 2014;82(5):310-318. [CrossRef]
85. Homma TK, Krepischi ACV, Furuya TK, et al. Recurrent copy number variants associated with syndromic short stature of unknown cause. Horm Res Paediatr. 2018;89(1):13-21. [CrossRef]
86. Marchini A, Ogata T, Rappold GA. A track record on SHOX: from basic research to complex models and therapy. Endocr Rev. 2016;37(4):417-448. [CrossRef]
87. Hauer NN, Sticht H, Boppudi S, et al. Genetic screening confirms heterozygous mutations in ACAN as a major cause of idiopathic short stature. Sci Rep. 2017;7(1):12225. [CrossRef]
88. Vasques GA, Amano N, Docko AJ, et al. Heterozygous mutations in natriuretic peptide receptor- B (NPR2) gene as a cause of short stature in patients initially classified as idiopathic short stature. J Clin Endocrinol Metab. 2013;98(10):E1636 -E1644. [CrossRef]
89. Wang SR, Carmichael H, Andrew SF, et al. Largescale pooled next-generation sequencing of 1077 genes to identify genetic causes of short stature. J Clin Endocrinol Metab. 2013;98(8):E142 8-E1437. [CrossRef]
90. Hattori A, Katoh-Fukui Y, Nakamura A, et al. Next generation sequencing-based mutation screening of 86 patients with idiopathic short stature. Endocr J. 2017;64(10):947-954. [CrossRef]
91. Yang L, Zhang C, Wang W, et al. Pathogenic gene screening in 91 Chinese patients with short stature of unknown etiology with a targeted nextgeneration sequencing panel. BMC Med Genet. 2018;19(1):212. [CrossRef]
92. Kim YM, Lee YJ, Park JH, et al. High diagnostic yield of clinically unidentifiable syndromic growth disorders by targeted exome sequencing. Clin Genet. 2017;92(6):594-605. [CrossRef]
93. Homma TK, Freire BL, Honjo Kawahira RS, et al. Genetic disorders in prenatal onset syndromic short stature identified by exome sequencing. J Pediatr. 2019;215:192-198. [CrossRef]
94. Hauer NN, Popp B, Schoeller E, et al. Clinical relevance of systematic phenotyping and exome sequencing in patients with short stature. Genet Med. 2018;20(6):630-638. [CrossRef]
95. Huang Z, Sun Y, Fan Y, et al. Genetic evaluation of 114 Chinese short stature children in the next generation era: a single center study. Cell Physiol Biochem. 2018;49(1):295-305. [CrossRef]
96. Piedrahita JA. The role of imprinted genes in fetal growth abnormalities. Birth Defects Res A Clin Mol Teratol. 2011;91(8):682-692. [CrossRef]
97. Wakeling EL, Brioude F, Lokulo-Sodipe O, et al. Diagnosis and management of Silver–Russell syndrome: first international consensus statement. Nat Rev Endocrinol. 2017;13(2):105-124. [CrossRef]
98. Stessman HA, Turner TN, Eichler EE. Molecular subtyping and improved treatment of neurodevelopmental disease. Genome Med. 2016;8(1):22. [CrossRef]

APA	turkyilmaz a, DÖNMEZ A, Cayir A (2022). A Genetic Approach in the Evaluation of Short Stature. , 179 - 186. 10.5152/eurasianjmed.2022.22171
Chicago	turkyilmaz ayberk,DÖNMEZ AYŞE SENA,Cayir Atilla A Genetic Approach in the Evaluation of Short Stature. (2022): 179 - 186. 10.5152/eurasianjmed.2022.22171
MLA	turkyilmaz ayberk,DÖNMEZ AYŞE SENA,Cayir Atilla A Genetic Approach in the Evaluation of Short Stature. , 2022, ss.179 - 186. 10.5152/eurasianjmed.2022.22171
AMA	turkyilmaz a,DÖNMEZ A,Cayir A A Genetic Approach in the Evaluation of Short Stature. . 2022; 179 - 186. 10.5152/eurasianjmed.2022.22171
Vancouver	turkyilmaz a,DÖNMEZ A,Cayir A A Genetic Approach in the Evaluation of Short Stature. . 2022; 179 - 186. 10.5152/eurasianjmed.2022.22171
IEEE	turkyilmaz a,DÖNMEZ A,Cayir A "A Genetic Approach in the Evaluation of Short Stature." , ss.179 - 186, 2022. 10.5152/eurasianjmed.2022.22171
ISNAD	turkyilmaz, ayberk vd. "A Genetic Approach in the Evaluation of Short Stature". (2022), 179-186. https://doi.org/10.5152/eurasianjmed.2022.22171

APA	turkyilmaz a, DÖNMEZ A, Cayir A (2022). A Genetic Approach in the Evaluation of Short Stature. Eurasian Journal of Medicine, 54(1), 179 - 186. 10.5152/eurasianjmed.2022.22171
Chicago	turkyilmaz ayberk,DÖNMEZ AYŞE SENA,Cayir Atilla A Genetic Approach in the Evaluation of Short Stature. Eurasian Journal of Medicine 54, no.1 (2022): 179 - 186. 10.5152/eurasianjmed.2022.22171
MLA	turkyilmaz ayberk,DÖNMEZ AYŞE SENA,Cayir Atilla A Genetic Approach in the Evaluation of Short Stature. Eurasian Journal of Medicine, vol.54, no.1, 2022, ss.179 - 186. 10.5152/eurasianjmed.2022.22171
AMA	turkyilmaz a,DÖNMEZ A,Cayir A A Genetic Approach in the Evaluation of Short Stature. Eurasian Journal of Medicine. 2022; 54(1): 179 - 186. 10.5152/eurasianjmed.2022.22171
Vancouver	turkyilmaz a,DÖNMEZ A,Cayir A A Genetic Approach in the Evaluation of Short Stature. Eurasian Journal of Medicine. 2022; 54(1): 179 - 186. 10.5152/eurasianjmed.2022.22171
IEEE	turkyilmaz a,DÖNMEZ A,Cayir A "A Genetic Approach in the Evaluation of Short Stature." Eurasian Journal of Medicine, 54, ss.179 - 186, 2022. 10.5152/eurasianjmed.2022.22171
ISNAD	turkyilmaz, ayberk vd. "A Genetic Approach in the Evaluation of Short Stature". Eurasian Journal of Medicine 54/1 (2022), 179-186. https://doi.org/10.5152/eurasianjmed.2022.22171