Lack of aberrations of the BMP4, BMP2, and PTX1 genes in a patient with pituitary hypoplasia, os odontoideum, renal dysplasia, and right leg anomalies.
We report on a 15-year-old girl who presented with pituitary hypoplasia, os odontoideum, renal dysplasia, an asymmetrically short right leg, and postaxial hypodactyly of the right foot. Her endocrinological data showed anterior pituitary hormone deficiency. The fact that she had healthy parents and an elder sister suggests that she had either a de novo mutation or autosomal recessive inheritance. We speculated that bone morphogenetic protein 4 (BMP4), BMP2, or pituitary homeobox 1 (PTX1) might be the responsible genes in this patient based on the similarity of her clinical symptoms and phenotypes to knock-out mice of these genes. We performed mutation analysis of these genes by direct sequencing of genomic DNA. In BMP2 gene, AGA right curved arrow AGT transversion in exon 3, converting arginine to serine was detected. In PTX1 gene, transversion of GCC right curved arrow GGC in exon 2, converting alanine to glycine at codon 184 was found in the patient and controls. We did not find any non-sense mutations although 5 polymorphisms of these genes were found. This constellation of findings may represent a new entity of congenital combined pituitary hormone deficiency.
Goto
Masahiro
M
Department of Pediatrics, Graduate School of Medicine, University of Tokyo, Japan.
Takita
Junko
J
Hashimoto
Nobuko
N
Tateshita
Fumie
F
Toyoji
Hirofumi
H
Kato
Hitoshi
H
Egi
Shinzo
S
Hayashi
Yasuhide
Y
D000293:Adolescent; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000235:genetics*; D002869:Chromosome Aberrations; D003062:Codon; D004252:DNA Mutational Analysis; D005091:Exons; D005260:Female; D018398:Homeodomain Proteins / Q000235:genetics*; D006801:Humans; D007593:Joint Instability / Q000235:genetics*; D007668:Kidney / Q000002:abnormalities / Q000473:pathology*; D017880:Limb Deformities, Congenital / Q000235:genetics*; D009809:Odontoid Process / Q000293:injuries*; D051761:Paired Box Transcription Factors; D010902:Pituitary Gland / Q000002:abnormalities / Q000473:pathology*; D011110:Polymorphism, Genetic; D014057:Tomography, X-Ray Computed; D014157:Transcription Factors / Q000235:genetics*; D016212:Transforming Growth Factor beta
C525718:BMP2 protein, human; C525809:BMP4 protein, human; C525719:Bmp2 protein, mouse; C525810:Bmp4 protein, mouse; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D003062:Codon; D018398:Homeodomain Proteins; D051761:Paired Box Transcription Factors; D014157:Transcription Factors; D016212:Transforming Growth Factor beta; C101485:homeobox protein PITX1