RGD Reference Report - Expansion of the phenotype of Kosaki overgrowth syndrome. - Rat Genome Database

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Expansion of the phenotype of Kosaki overgrowth syndrome.

Authors: Minatogawa, Mari  Takenouchi, Toshiki  Tsuyusaki, Yu  Iwasaki, Fuminori  Uehara, Tomoko  Kurosawa, Kenji  Kosaki, Kenjiro  Curry, Cynthia J 
Citation: Minatogawa M, etal., Am J Med Genet A. 2017 Sep;173(9):2422-2427. doi: 10.1002/ajmg.a.38310. Epub 2017 Jun 22.
RGD ID: 13442504
Pubmed: PMID:28639748   (View Abstract at PubMed)
DOI: DOI:10.1002/ajmg.a.38310   (Journal Full-text)

Skeletal overgrowth is a characteristic of several genetic disorders that are linked to specific molecular signaling cascades. Recently, we established a novel overgrowth syndrome (Kosaki overgrowth syndrome, OMIM #616592) arising from a de novo mutation in PDGFRB, that is, c.1751C>G p.(Pro584Arg). Subsequently, other investigators provided in vitro molecular evidence that this specific mutation in the juxtamembrane domain of PDGFRB causes an overgrowth phenotype and is the first gain-of-function point mutation of PDGFRB to be reported in humans. Here, we report the identification of a mutation in PDGFRB, c.1696T>C p.(Trp566Arg), in two unrelated patients with skeletal overgrowth, further confirming the existence of PDGFRB-related overgrowth syndrome arising from mutations in the juxtamembrane domain of PDGFRB. A review of all four of these patients with an overgrowth phenotype and PDGFRB mutations revealed postnatal skeletal overgrowth, premature aging, cognitive impairment, neurodegeneration, and a prominent connective tissue component to this complex phenotype. From a functional standpoint, hypermorphic mutations in PDGFRB lead to Kosaki overgrowth syndrome, infantile myofibromatosis (OMIM #228550), and Penttinen syndrome (OMIM #601812), whereas hypomorphic mutations lead to idiopathic basal ganglia calcification (OMIM #615007). In conclusion, a specific class of mutations in PDGFRB causes a clinically recognizable syndromic form of skeletal overgrowth.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDGFRBHumanKosaki Overgrowth Syndrome  IAGP DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 
PdgfrbRatKosaki Overgrowth Syndrome  ISOPDGFRB (Homo sapiens)DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 
PdgfrbMouseKosaki Overgrowth Syndrome  ISOPDGFRB (Homo sapiens)DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
PDGFRBHumanAbnormally lax or hyperextensible skin  IAGP DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 
PDGFRBHumanFragile skin  IAGP DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 
PDGFRBHumanIntellectual disability  IAGP DNA:mutation:cds:c.1696T>C p.W566R(human)RGD 
Objects Annotated

Genes (Rattus norvegicus)
Pdgfrb  (platelet derived growth factor receptor beta)

Genes (Mus musculus)
Pdgfrb  (platelet derived growth factor receptor, beta polypeptide)

Genes (Homo sapiens)
PDGFRB  (platelet derived growth factor receptor beta)


Additional Information