Table 1.

Summary of Molecular Genetic Testing Used in PROP1-Related Combined Pituitary Hormone Deficiency

Gene 1Test MethodProportion of Probands with a Pathogenic Variant Detectable by This Method
PROP1Sequence analysis 2, 3>98% 4
Deletion/duplication analysis 5See footnote 6

See Table A. Genes and Databases for chromosome locus and protein. See Molecular Genetics for information on allelic variants detected in this gene.


Sequence analysis detects variants that are benign, likely benign, of uncertain significance, likely pathogenic, or pathogenic. Pathogenic variants may include small intragenic deletions/insertions and missense, nonsense, and splice site variants; typically, exon or whole-gene deletions/duplications are not detected. For issues to consider in interpretation of sequence analysis results, click here.


The common recurring PROP1 deletion in which three AG repeats are reduced to two AG repeats (c.301_302delAG) accounts for 55% of alleles in familial cases and 12% of alleles in simplex cases of CPHD (i.e., single occurrence in a family).


The proportion of CPHD caused by pathogenic variants in PROP1 varies by study suggesting either bias in ascertainment in some studies or variation in the frequency of PROP1 pathogenic variants between populations of different ethnic origins [reviewed in de Graaff et al 2010]. See Table 2.


Testing that identifies exon or whole-gene deletions/duplications not detectable by sequence analysis of the coding and flanking intronic regions of genomic DNA. Included in the variety of methods that may be used are: quantitative PCR, long-range PCR, multiplex ligation-dependent probe amplification (MLPA), and chromosomal microarray (CMA) that includes this gene/chromosome segment.


Abrão et al [2006] reported complete deletion of PROP1 in two sibs with GH deficiency associated with other pituitary hormone deficiencies (TSH, PRL and gonadotropins). One of the sibs also had an evolving cortisol deficiency. Kelberman et al [2009] identified a homozygous deletion of PROP1 in two individuals with CPHD born to consanguineous parents. Zhang et al [2010] reported in two pedigrees with CPHD a deletion of a segment of about 53.2 kb encompassing PROP1 and adjacent sequences.

From: PROP1-Related Combined Pituitary Hormone Deficiency

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