Molekulargenetische Diagnostik
Praxis Dr. Mato Nagel

Kombinierter Hypophysenhormon-Mangel

Der kombinierter Hypophysenhormon-Mangel ist eine Gruppe von Erkrankungen mit Entwicklungsstörungen der Hypophyse. Ursächlich sind Mutationen in verschiedenen TRanskriptionsfaktoren, die für die Entwicklung der Hypophyse vernantwortlich sind. Klinische Erscheinungen sind durch den Hypophysenhormon-Mangel geprägt. Hinzu können aber noch weitere Störungen im Zentralnervensystem vorhanden sein. Die Vererbung kann sowohl dominant als auch rezessiv erfolgen.

Gliederung

Erbliche Erkrankungen der Hypophyse
Familiäre und sporadische Hypophysenadenome
Kombinierter Hypophysenhormon-Mangel
Hyophysenhormonmangel Typ 1
POU1F1
Hyophysenhormonmangel Typ 2
PROP1
Hyophysenhormonmangel Typ 3
LHX3
Hyophysenhormonmangel Typ 4
LHX4
Hyophysenhormonmangel Typ 5
HESX1

Referenzen:

1.

None (2005) Growth hormone deficiency and combined pituitary hormone deficiency: does the genotype matter?

[^]
2.

Rogol AD et. al. (1976) Congenital hypothyroidism in a young man with growth hormone, thyrotropin, and prolactin deficiencies.

[^]
3.

Tatsumi K et. al. (1992) Cretinism with combined hormone deficiency caused by a mutation in the PIT1 gene.

[^]
4.

Ohta K et. al. (1992) Mutations in the Pit-1 gene in children with combined pituitary hormone deficiency.

[^]
5.

Radovick S et. al. (1992) A mutation in the POU-homeodomain of Pit-1 responsible for combined pituitary hormone deficiency.

[^]
6.

Pfäffle RW et. al. (1992) Mutation of the POU-specific domain of Pit-1 and hypopituitarism without pituitary hypoplasia.

[^]
7.

Wit JM et. al. (1989) Total deficiency of growth hormone and prolactin, and partial deficiency of thyroid stimulating hormone in two Dutch families: a new variant of hereditary pituitary deficiency.

[^]
8.

McArthur RG et. al. (1985) The natural history of familial hypopituitarism.

[^]
9.

McKusick VA et. al. (1967) General Tom Thumb and other midgets.

[^]
10.

de Zegher F et. al. (1995) The prenatal role of thyroid hormone evidenced by fetomaternal Pit-1 deficiency.

[^]
11.

Irie Y et. al. (1995) A novel E250X mutation of the PIT1 gene in a patient with combined pituitary hormone deficiency.

[^]
12.

Okamoto N et. al. (1994) Monoallelic expression of normal mRNA in the PIT1 mutation heterozygotes with normal phenotype and biallelic expression in the abnormal phenotype.

[^]
13.

Pellegrini-Bouiller I et. al. (1996) A new mutation of the gene encoding the transcription factor Pit-1 is responsible for combined pituitary hormone deficiency.

[^]
14.

Aarskog D et. al. (1997) Pituitary dwarfism in the R271W Pit-1 gene mutation.

[^]
15.

Pernasetti F et. al. (1998) Pro239Ser: a novel recessive mutation of the Pit-1 gene in seven Middle Eastern children with growth hormone, prolactin, and thyrotropin deficiency.

[^]
16.

Vallette-Kasic S et. al. (2001) Combined pituitary hormone deficiency due to the F135C human Pit-1 (pituitary-specific factor 1) gene mutation: functional and structural correlates.

[^]
17.

Hendriks-Stegeman BI et. al. (2001) Combined pituitary hormone deficiency caused by compound heterozygosity for two novel mutations in the POU domain of the Pit1/POU1F1 gene.

[^]
18.

Hashimoto Y et. al. (2003) A novel nonsense mutation in the Pit-1 gene: evidence for a gene dosage effect.

[^]
19.

Turton JP et. al. (2005) Novel mutations within the POU1F1 gene associated with variable combined pituitary hormone deficiency.

[^]
20.

Miyata I et. al. (2006) Identification and functional analysis of the novel S179R POU1F1 mutation associated with combined pituitary hormone deficiency.

[^]
21.

Schuelke M et. al. (2002) Septo-optic dysplasia associated with a new mitochondrial cytochrome b mutation.

[^]
22.

Freyd G et. al. (1990) Novel cysteine-rich motif and homeodomain in the product of the Caenorhabditis elegans cell lineage gene lin-11.

[^]
23.

Way JC et. al. (1988) mec-3, a homeobox-containing gene that specifies differentiation of the touch receptor neurons in C. elegans.

[^]
24.

Tsuchida T et. al. (1994) Topographic organization of embryonic motor neurons defined by expression of LIM homeobox genes.

[^]
25.

Zhadanov AB et. al. (1995) Expression pattern of the murine LIM class homeobox gene Lhx3 in subsets of neural and neuroendocrine tissues.

[^]
26.

Zhadanov AB et. al. (1995) Genomic structure and chromosomal localization of the mouse LIM/homeobox gene Lhx3.

[^]
27.

Mbikay M et. al. (1995) Linkage mapping of the gene for the LIM-homeoprotein LIM3 (locus Lhx3) to mouse chromosome 2.

[^]
28.

Sheng HZ et. al. (1996) Specification of pituitary cell lineages by the LIM homeobox gene Lhx3.

[^]
29.

Sharma K et. al. (1998) LIM homeodomain factors Lhx3 and Lhx4 assign subtype identities for motor neurons.

[^]
30.

Sloop KW et. al. (1999) Differential activation of pituitary hormone genes by human Lhx3 isoforms with distinct DNA binding properties.

[^]
31.

Sloop KW et. al. (2000) Analysis of the human LHX3 neuroendocrine transcription factor gene and mapping to the subtelomeric region of chromosome 9.

[^]
32.

Netchine I et. al. (2000) Mutations in LHX3 result in a new syndrome revealed by combined pituitary hormone deficiency.

[^]
33.

Sloop KW et. al. (2000) Molecular analysis of LHX3 and PROP-1 in pituitary hormone deficiency patients with posterior pituitary ectopia.

[^]
34.

Sharma K et. al. (2000) Genetic and epigenetic mechanisms contribute to motor neuron pathfinding.

[^]
35.

Thaler JP et. al. (2002) LIM factor Lhx3 contributes to the specification of motor neuron and interneuron identity through cell-type-specific protein-protein interactions.

[^]
36.

Lee SK et. al. (2003) Synchronization of neurogenesis and motor neuron specification by direct coupling of bHLH and homeodomain transcription factors.

[^]
37.

Bhangoo AP et. al. (2006) Clinical case seminar: a novel LHX3 mutation presenting as combined pituitary hormonal deficiency.

[^]
38.

Pfaeffle RW et. al. (2007) Four novel mutations of the LHX3 gene cause combined pituitary hormone deficiencies with or without limited neck rotation.

[^]
39.

Rajab A et. al. (2008) Novel mutations in LHX3 are associated with hypopituitarism and sensorineural hearing loss.

[^]
40.

Wu W et. al. (1998) Mutations in PROP1 cause familial combined pituitary hormone deficiency.

[^]
41.

Fofanova O et. al. (1998) Compound heterozygous deletion of the PROP-1 gene in children with combined pituitary hormone deficiency.

[^]
42.

Cogan JD et. al. (1998) The PROP1 2-base pair deletion is a common cause of combined pituitary hormone deficiency.

[^]
43.

Flück C et. al. (1998) Phenotypic variability in familial combined pituitary hormone deficiency caused by a PROP1 gene mutation resulting in the substitution of Arg-->Cys at codon 120 (R120C).

[^]
44.

Rosenbloom AL et. al. (1999) Clinical and biochemical phenotype of familial anterior hypopituitarism from mutation of the PROP1 gene.

[^]
45.

Mendonca BB 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.

[^]
46.

Pernasetti F 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.

[^]
47.

Agarwal G et. al. (2000) Adrenocorticotropin deficiency in combined pituitary hormone deficiency patients homozygous for a novel PROP1 deletion.

[^]
48.

Riepe FG et. al. (2001) Longitudinal imaging reveals pituitary enlargement preceding hypoplasia in two brothers with combined pituitary hormone deficiency attributable to PROP1 mutation.

[^]
49.

Vallette-Kasic S et. al. (2001) PROP1 gene screening in patients with multiple pituitary hormone deficiency reveals two sites of hypermutability and a high incidence of corticotroph deficiency.

[^]
50.

Lee JK et. al. (2004) Long-term growth hormone therapy in adulthood results in significant linear growth in siblings with a PROP-1 gene mutation.

[^]
51.

Böttner A et. al. (2004) PROP1 mutations cause progressive deterioration of anterior pituitary function including adrenal insufficiency: a longitudinal analysis.

[^]
52.

Reynaud R et. al. (2004) A familial form of congenital hypopituitarism due to a PROP1 mutation in a large kindred: phenotypic and in vitro functional studies.

[^]
53.

Wales JK et. al. (1996) Evidence for possible Mendelian inheritance of septo-optic dysplasia.

[^]
54.

Dattani MT et. al. (1998) Mutations in the homeobox gene HESX1/Hesx1 associated with septo-optic dysplasia in human and mouse.

[^]
55.

Thomas PQ et. al. (2001) Heterozygous HESX1 mutations associated with isolated congenital pituitary hypoplasia and septo-optic dysplasia.

[^]
56.

Brickman JM et. al. (2001) Molecular effects of novel mutations in Hesx1/HESX1 associated with human pituitary disorders.

[^]
57.

Tajima T et. al. (2003) Sporadic heterozygous frameshift mutation of HESX1 causing pituitary and optic nerve hypoplasia and combined pituitary hormone deficiency in a Japanese patient.

[^]
58.

Carvalho LR et. al. (2003) A homozygous mutation in HESX1 is associated with evolving hypopituitarism due to impaired repressor-corepressor interaction.

[^]
59.

Sobrier ML et. al. (2006) Novel HESX1 mutations associated with a life-threatening neonatal phenotype, pituitary aplasia, but normally located posterior pituitary and no optic nerve abnormalities.

[^]
60.

McNay DE et. al. (2007) HESX1 mutations are an uncommon cause of septooptic dysplasia and hypopituitarism.

[^]
61.

Machinis K et. al. (2001) Syndromic short stature in patients with a germline mutation in the LIM homeobox LHX4.

[^]
62.

Tajima T 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.

[^]
63.

Pfaeffle RW et. al. (2008) Three novel missense mutations within the LHX4 gene are associated with variable pituitary hormone deficiencies.

[^]
64.

Voss JW et. al. (1992) Anterior pituitary development: short tales from dwarf mice.

[^]
65.

Steiner MM et. al. (1965) Absence of pituitary gland, hypothyroidism, hypoadrenalism and hypogonadism in a 17-year-old dwarf.

[^]
66.

None (1969) Congenital absence of hypoplasia of the endocrine glands.

[^]
67.

Rosenfield RL et. al. (1967) Idiopathic anterior hypopituitarism in one of monozygous twins.

[^]
68.

Pinto G et. al. (1997) Pituitary stalk interruption syndrome: a clinical-biological-genetic assessment of its pathogenesis.

[^]
69.

Sadeghi-Nejad A et. al. (1974) A familial syndrome of isolated "aplasia" of the anterior pituitary. Diagnostic studies and treatment in the neonatal period.

[^]
70.

None (1953) [The role of hereditary factors in growth disorders].

[^]
71.

KIRCHHOFF HW et. al. (1954) [Clinical, hereditary and constitutional studies of primordial dwarfs].

[^]
72.

None (1964) STUDIES IN ISOLATES.

[^]
73.

Voutetakis A et. al. (2004) Pituitary magnetic resonance imaging in 15 patients with Prop1 gene mutations: pituitary enlargement may originate from the intermediate lobe.

[^]
74.

Ferrier PE et. al. (1969) Familial pituitary dwarfism associated with an abnormal sella turcica.

[^]
75.

Rush JA et. al. (1978) Septo-optic dysplasia (de Morsier syndrome).

[^]
76.

Purdy F et. al. (1979) Maternal factors in septo-optic dysplasia.

[^]
77.

Patel H et. al. (1975) Optic nerve hypoplasia with hypopituitarism. Septo-optic dysplasia with hypopituitarism.

[^]
78.

Benner JD et. al. (1990) Septo-optic dysplasia in two siblings.

[^]
79.

Blethen SL et. al. (1985) Hypopituitarism and septooptic "dysplasia" in first cousins.

[^]
80.

Hoyt WF et. al. (1970) Septo-optic dysplasia and pituitary dwarfism.

[^]
81.

Harris RJ et. al. (1972) Septo-optic dysplasia with growth hormone deficiency (De Morsier syndrome).

[^]
82.

Brook CG et. al. (1972) Septo-optic dysplasia.

[^]
83.

Stewart C et. al. (1983) Septo-optic dysplasia and median cleft face syndrome in a patient with isolated growth hormone deficiency and hyperprolactinemia.

[^]
84.

Brodsky MC et. al. (1997) Sudden death in septo-optic dysplasia. Report of 5 cases.

[^]
85.

None (1962) Median craioencephalic dysraphias and olfactogenital dysplasia.

[^]
86.

Birkebaek NH et. al. (2003) Endocrine status in patients with optic nerve hypoplasia: relationship to midline central nervous system abnormalities and appearance of the hypothalamic-pituitary axis on magnetic resonance imaging.

[^]
87.

Stevens CA et. al. (2004) Septo-optic dysplasia and amniotic bands: further evidence for a vascular pathogenesis.

[^]
88.

Harrison IM et. al. (2004) Septo-optic dysplasia with digital anomalies--a recurrent pattern syndrome.

[^]
89.

Webb EA et. al. (2010) Septo-optic dysplasia.

[^]