Mutations in the pericentrin (PCNT) gene cause primordial dwarfism
Anita Rauch1, Christian T Thiel, Detlev Schindler
1Institute of Human Genetics, University Hospital Erlangen, Friedrich-Alexander University Erlangen-Nuremberg, Erlangen, Germany. Anita.Rauch@humgenet.uni-erlangen.de
Science (New York, N.Y.)
|January 5, 2008
Summary
Genetic mutations in the pericentrin (PCNT) gene cause primordial dwarfism. This rare condition leads to extreme short stature and microcephaly, impacting human growth processes.
Area of Science:
- Genetics
- Human Growth
- Cell Biology
Background:
- Extreme short stature provides insights into human growth.
- Microcephalic osteodysplastic primordial dwarfism type II (MOPD II) is a rare inherited condition.
- Centrosomal genes are crucial for cell division and development.
Purpose of the Study:
- To identify the genetic cause of MOPD II.
- To understand the role of the pericentrin (PCNT) gene in human growth and development.
Main Methods:
- Genetic linkage analysis was performed on 25 patients with MOPD II.
- Analysis focused on mutations in the pericentrin (PCNT) gene located on chromosome 21q22.3.
Main Results:
- Biallelic loss-of-function mutations in the PCNT gene were identified as the cause of MOPD II.
- Absence of PCNT leads to disorganized mitotic spindles and chromosome missegregation.
- Patients exhibit extreme short stature (average adult height ~100 cm) and severe microcephaly, with near-normal intelligence.
Conclusions:
- The PCNT gene is essential for normal human growth, particularly head and skeletal development.
- PCNT mutations disrupt cell division, leading to the characteristic features of MOPD II.
- This finding expands the understanding of genetic disorders affecting microcephaly and primordial dwarfism.
Related Concept Videos
01:43Incomplete Dominance
Gregor Mendel's work (1822 - 1884) was primarily focused on pea plants. Through his initial experiments, he determined that every gene in a diploid cell has two variants called alleles inherited from each parent. He suggested that amongst these two alleles, one allele is dominant in character and the other recessive. The combination of alleles determines the phenotype of a gene in an organism.
02:30Genomic Imprinting and Inheritance
Diploid organisms inherit genetic material through chromosomes from both parents. Copies of the same gene are known as alleles. In most cases, both alleles are simultaneously expressed and allow various cellular processes to function optimally. If one of the alleles is missing or mutated, the expression of the other allele can compensate; however, this is not true for all genes.
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
The expression of some genes depends on which parent passed the gene to the offspring, through a phenomenon known as...
01:33Pleiotropy
Pleiotropy is the phenomenon in which a single gene impacts multiple, seemingly unrelated phenotypic traits. For example, defects in the SOX10 gene cause Waardenburg Syndrome Type 4, or WS4, which can cause defects in pigmentation, hearing impairments, and an absence of intestinal contractions necessary for elimination. This diversity of phenotypes results from the expression pattern of SOX10 in early embryonic and fetal development. SOX10 is found in neural crest cells that form melanocytes,...
01:22Microtubules in Signaling
The primary cilium, made up of microtubules, acts as antennae on the cell surfaces for relaying external stimuli into the cells. These fine hair-like structures are present, generally one per cell. These are non-motile cilia in a 9+0 microtubules arrangement, where the central pair of microtubules are absent. The primary cilia arise from the basal body embedded in the cell membrane. Intraflagellar transport (IFT) carries requisite proteins from the cytoplasm to the cilium because the primary...
02:23Abnormal Proliferation
Under normal conditions, most adult cells remain in a non-proliferative state unless stimulated by internal or external factors to replace lost cells. Abnormal cell proliferation is a condition in which the cell's growth exceeds and is uncoordinated with normal cells. In such situations, cell division persists in the same excessive manner even after cessation of the stimuli, leading to persistent tumors. The tumor arises from the damaged cells that replicate to pass the damage to the daughter...
02:25Centrosome Duplication
The primary microtubule organizing center (MTOC) in animal cells is the centrosome. A centrosome has two cylindrical centrioles at its core. Each centriole consists of nine sets of three microtubules held together by proteins. The centrioles are positioned at right angles to each other and surrounded by a shapeless protein cloud called the pericentriolar matrix, or pericentriolar material (PCM).
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...
To ensure that each daughter cell receives a centrosome after cell division, centrosome duplication...