Gradual Loss of ACTH Due to a Novel Mutation in LHX4: Comprehensive Mutation Screening in Japanese Patients with Congenital Hypopituitarism

PLoS ONE

Volumn 7, Issue 9, 2012, Pages

  Takagi, Masaki ^a,b   Ishii, Tomohiro ^a   Inokuchi, Mikako ^a   Amano, Naoko ^a   Narumi, Satoshi ^a   Asakura, Yumi ^c   Muroya, Koji ^c   Hasegawa, Yukihiro ^b   Adachi, Masanori ^c   Hasegawa, Tomonobu ^a  

^a KEIO UNIVERSITY SCHOOL OF MEDICINE   (Japan)

^b TOKYO METROPOLITAN CHILDREN'S MEDICAL CENTER   (Japan)

^c KANAGAWA CHILDREN'S MEDICAL CENTER   (Japan)

Author keywords

[No Author keywords available]

Indexed keywords

CORTICOTROPIN; RECOMBINANT GROWTH HORMONE; THYROXINE;

ADOLESCENT; ADULT; ARTICLE; CHILD; CLINICAL FEATURE; CONTROLLED STUDY; EXON; FEMALE; GENE; GENE CONTROL; GENE DOSAGE; GENE MUTATION; GENETIC ANALYSIS; GENETIC SCREENING; GLI2 GENE; GROWTH HORMONE DEFICIENCY; HESX1 GENE; HETEROZYGOSITY; HUMAN; HYPOPITUITARISM; HYPOTHALAMUS HYPOPHYSIS ADRENAL SYSTEM; INTRON; JAPANESE; LHX3 GENE; LHX4 GENE; MAJOR CLINICAL STUDY; MALE; MULTIPLEX LIGATION DEPENDENT PROBE AMPLIFICATION; NEUROIMAGING; OTX2 GENE; POU1F1 GENE; PRESCHOOL CHILD; PREVALENCE; PROP1 GENE; PROTEIN DOMAIN; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION; SCHOOL CHILD; SOX2 GENE; SOX3 GENE; TRANSACTIVATION;

ADRENOCORTICOTROPIC HORMONE; AMINO ACID SEQUENCE; ANIMALS; ASIAN CONTINENTAL ANCESTRY GROUP; GENE DOSAGE; HETEROZYGOTE; HUMANS; HYPOPITUITARISM; LIM-HOMEODOMAIN PROTEINS; MOLECULAR SEQUENCE DATA; MUTATION; PEDIGREE; PITUITARY GLAND; SEQUENCE ALIGNMENT; TRANSCRIPTION FACTORS;

EID: 84866683883     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0046008     Document Type: Article

References (25)

1. Romero CJ, Nesi-França S, Radovick S, (2009) The molecular basis of hypopituitarism. Trends Endocrinol Metab 20: 506-516.
2. Kelberman D, Rizzoti K, Lovell-Badge R, Robinson IC, Dattani MT, (2009) Genetic regulation of pituitary gland development in human and mouse. Endocr Rev 30: 790-829.
3. Pfäffle R, Klammt J, (2011) Pituitary transcription factors in the aetiology of combined pituitary hormone deficiency. Best Pract Res Clin Endocrinol Metab 25: 43-60.
4. de Graaff LC, Argente J, Veenma DC, Drent ML, Uitterlinden AG, et al. (2010) PROP1, HESX1, POU1F1, LHX3 and LHX4 mutation and deletion screening and GH1 P89L and IVS3+1/+2 mutation screening in a Dutch nationwide cohort of patients with combined pituitary hormone deficiency. Horm Res Paediatr 73: 363-371.
5. Dateki S, Fukami M, Uematsu A, Kaji M, Iso M, et al. (2010) Mutation and gene copy number analyses of six pituitary transcription factor genes in 71 patients with combined pituitary hormone deficiency: identification of a single patient with LHX4 deletion. J Clin Endocrinol Metab 95: 4043-4047.
6. Reynaud R, Gueydan M, Saveanu A, Vallette-Kasic S, Enjalbert A, et al. (2006) Genetic screening of combined pituitary hormone deficiency: experience in 195 patients. J Clin Endocrinol Metab 91: 3329-3336.
7. Cogan JD, Wu W, Phillips JA 3rd, Arnhold IJ, Agapito A, et al. (1998) The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency. J Clin Endocrinol Metab 83: 3346-3349.
8. McLennan K, Jeske Y, Cotterill A, Cowley D, Penfold J, et al. (2003) Combined pituitary hormone deficiency in Australian children: clinical and genetic correlates. Clin Endocrinol 58: 785-794.
9. Rainbow LA, Rees SA, Shaikh MG, Shaw NJ, Cole T, et al. (2005) Mutation analysis of POUF-1, PROP-1 and HESX-1 show low frequency of mutations in children with sporadic forms of combined pituitary hormone deficiency and septo-optic dysplasia. Clin Endocrinol (Oxf) 62: 163-168.
10. Machinis K, Amselem S, (2005) Functional relationship between LHX4 and POU1F1 in light of the LHX4 mutation identified in patients with pituitary defects. J Clin Endocrinol Metab 90: 5456-5462.
11. Radovick S, Nations M, Du Y, Berg LA, Weintraub BD, et al. (1992) A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency. Science 257: 1115-1118.
12. Crofton PM, Don-Wauchope AC, Bath LE, Kelnar CJ, (2004) Cortisol responses to the insulin hypoglycaemia test in children. Horm Res. 61: 92-97.
13. Machinis K, Pantel J, Netchine I, Léger J, Camand OJ, et al. (2001) Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4. Am J Hum Genet 69: 961-968.
14. Tajima T, Hattori T, Nakajima T, Okuhara K, Tsubaki J, et al. (2007) A novel missense mutation (P366T) of the LHX4 gene causes severe combined pituitary hormone deficiency with pituitary hypoplasia, ectopic posterior lobe and a poorly developed sella turcica. Endocr J 54: 637-641.
15. Pfaeffle RW, Hunter CS, Savage JJ, Duran-Prado M, Mullen RD, et al. (2008) Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies. J Clin Endocrinol Metab 93: 1062-1071.
16. Castinetti F, Saveanu A, Reynaud R, Quentien MH, Buffin A, et al. (2008) A novel dysfunctional LHX4 mutation with high phenotypical variability in patients with hypopituitarism. J Clin Endocrinol Metab 93: 2790-2799.
17. Tajima T, Yorifuji T, Ishizu K, Fujieda K (2010) A novel mutation (V101A) of the LHX4 gene in a Japanese patient with combined pituitary hormone deficiency. Exp Clin Endocrinol Diabetes 118: 405-409.
18. Mendonca BB, Osorio MG, Latronico AC, Estefan V, Lo LS, et al. (1999) Longitudinal hormonal and pituitary imaging changes in two females with combined pituitary hormone deficiency due to deletion of A301, G302 in the PROP1 gene. J Clin Endocrinol Metab 84: 942-945.
19. Asteria C, Oliveira JH, Abucham J, Beck-Peccoz P, (2000) Central hypocortisolism as part of combined pituitary hormone deficiency due to mutations of PROP-1 gene. Eur J Endocrinol 143: 347-352.
20. Pernasetti F, Toledo SP, Vasilyev VV, Hayashida CY, Cogan JD, et al. (2000) Impaired adrenocorticotropin-adrenal axis in combined pituitary hormone deficiency caused by a two-base pair deletion (301-302delAG) in the prophet of Pit-1 gene. J Clin Endocrinol Metab 85: 390-397.
21. Bonfig W, Krude H, Schmidt H, (2011) A novel mutation of LHX3 is associated with combined pituitary hormone deficiency including ACTH deficiency, sensorineural hearing loss, and short neck-a case report and review of the literature. Eur J Pediatr 170: 1017-1021.
22. Ito J, Tanaka T, Horikawa R, Okada Y, Morita S, et al. (1993) Serum LH and FSH levels during GnRH tests and sleep in children. J Jpn Pediatr Soc (in Japanese) 97: 1789-1796.
23. Crofton PM, Don-Wauchope AC, Bath LE, Kelnar CJ, (2004) Cortisol responses to the insulin hypoglycaemia test in children. Horm Res 61: 92-97.
24. Fujieda K, Shimazu A, Hanyuu K, Tanaka T, Yokoya S, et al. (1996) Clinical evaluation of serum IGF-I, IGF-II and IGFBP-3 measured by IRMA kits in childhood. Clinical Endocrinology (in Japanese) 44: 1229-1239.
25. Japan Public Health Association (1996) Normal biochemical values in Japanese children (in Japanese). Tokyo: Sanko Press.