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Homozygous microdeletion of the POU1F1, CHMP2B, and VGLL3 genes in chromosome 3-A novel syndrome
- Source :
- American Journal of Medical Genetics Part A. 155:2242-2246
- Publication Year :
- 2011
- Publisher :
- Wiley, 2011.
-
Abstract
- Microdeletion syndromes include numerous syndromic phenotypes associated with intellectual disability and dysmorphic features. We report on a patient with a novel microdeletion of chromosomal region 3p11.2-p12.1 containing POU1F1, chromatin-modifying protein 2B (CHMP2B), and vestigial-like 3 (VGLL3) genes. Our patient was diagnosed as having a neonatal multiple pituitary hormone [growth hormone (GH), thyroid-stimulating hormone (TSH), and prolactin] deficiency. In addition to the typical findings associated with these hormonal deficiencies, she exhibited clinical features resembling those of Laron syndrome (frontal bossing, saddle nose, small chin, blue sclera, and acromicria), with moderate intellectual disability. She also displayed an unusual growth pattern characterized by unresponsiveness to high doses of GH replacement therapy during infancy and early childhood and an accelerated growth rate beginning at the age of 4.5 years. Insulin-like growth factor (IGF)-1 levels were consistently extremely low or undetectable. Extensive medical and genetic analysis ruled out primary and secondary GH insensitivity. The distinct phenotype and the peculiar growth pattern observed in this affected patient, not reported to have been observed in other cases with POU1F1 gene inactivity, suggest that the other two deleted genes play a possible role in the development of this syndrome. This hypothesis may be supported by the fact that both the CHMP2B and VGLL3 genes are expressed in the liver and the growth plate, the two main target organs of the GH/IGF-1 axis. The homozygous deletion of the CHMP2B gene, previously associated with frontotemporal dementia, may contribute to the intellectual disability observed in this patient.
- Subjects :
- medicine.medical_specialty
Somatotropic cell
Thyrotropin
Growth hormone deficiency
Thyroid hormone receptor beta
Frontal Bossing
Intellectual Disability
Internal medicine
Intellectual disability
Genetics
medicine
Laron syndrome
Humans
Abnormalities, Multiple
Insulin-Like Growth Factor I
Israel
Child
Genetics (clinical)
Endosomal Sorting Complexes Required for Transport
business.industry
medicine.disease
Laron Syndrome
Prolactin
Endocrinology
Liver
Growth Hormone
Chromosomal region
Premature Birth
Female
Chromosomes, Human, Pair 3
Chromosome Deletion
Transcription Factor Pit-1
business
Transcription Factors
Endocrine gland
Subjects
Details
- ISSN :
- 15524825
- Volume :
- 155
- Database :
- OpenAIRE
- Journal :
- American Journal of Medical Genetics Part A
- Accession number :
- edsair.doi.dedup.....33556452dbf1c037d078f32c3d0bfe6d