title: Genotypic and phenotypic spectrum in tricho-rhino-phalangeal syndrome types I and III.
abstract: Tricho-rhino-phalangeal syndrome (TRPS) is characterized by craniofacial and skeletal abnormalities. Three subtypes have been described: TRPS I, caused by mutations in the TRPS1 gene on chromosome 8; TRPS II, a microdeletion syndrome affecting the TRPS1 and EXT1 genes; and TRPS III, a form with severe brachydactyly, due to short metacarpals, and severe short stature, but without exostoses. To investigate whether TRPS III is caused by TRPS1 mutations and to establish a genotype-phenotype correlation in TRPS, we performed extensive mutation analysis and evaluated the height and degree of brachydactyly in patients with TRPS I or TRPS III. We found 35 different mutations in 44 of 51 unrelated patients. The detection rate (86%) indicates that TRPS1 is the major locus for TRPS I and TRPS III. We did not find any mutation in the parents of sporadic patients or in apparently healthy relatives of familial patients, indicating complete penetrance of TRPS1 mutations. Evaluation of skeletal abnormalities of patients with TRPS1 mutations revealed a wide clinical spectrum. The phenotype was variable in unrelated, age- and sex-matched patients with identical mutations, as well as in families. Four of the five missense mutations alter the GATA DNA-binding zinc finger, and six of the seven unrelated patients with these mutations may be classified as having TRPS III. Our data indicate that TRPS III is at the severe end of the TRPS spectrum and that it is most often caused by a specific class of mutations in the TRPS1 gene.
authors: Institut für Humangenetik, Universitätsklinikum, 45122 Essen, Germany. hj.luedecke@uni-essen.de
authors: H J
authors: HJ
authors: Lüdecke
authors: J
authors: J
authors: Schaper
authors: P
authors: P
authors: Meinecke
authors: P
authors: P
authors: Momeni
authors: S
authors: S
authors: Gross
authors: von Holtum D
authors: H
authors: H
authors: Hirche
authors: M J
authors: MJ
authors: Abramowicz
authors: B
authors: B
authors: Albrecht
authors: C
authors: C
authors: Apacik
authors: H J
authors: HJ
authors: Christen
authors: U
authors: U
authors: Claussen
authors: K
authors: K
authors: Devriendt
authors: E
authors: E
authors: Fastnacht
authors: A
authors: A
authors: Forderer
authors: U
authors: U
authors: Friedrich
authors: T H
authors: TH
authors: Goodship
authors: M
authors: M
authors: Greiwe
authors: H
authors: H
authors: Hamm
authors: R C
authors: RC
authors: Hennekam
authors: G K
authors: GK
authors: Hinkel
authors: M
authors: M
authors: Hoeltzenbein
authors: H
authors: H
authors: Kayserili
authors: F
authors: F
authors: Majewski
authors: M
authors: M
authors: Mathieu
authors: R
authors: R
authors: McLeod
authors: A T
authors: AT
authors: Midro
authors: U
authors: U
authors: Moog
authors: T
authors: T
authors: Nagai
authors: N
authors: N
authors: Niikawa
authors: K H
authors: KH
authors: Orstavik
authors: E
authors: E
authors: Plöchl
authors: C
authors: C
authors: Seitz
authors: J
authors: J
authors: Schmidtke
authors: L
authors: L
authors: Tranebjaerg
authors: M
authors: M
authors: Tsukahara
authors: B
authors: B
authors: Wittwer
authors: B
authors: B
authors: Zabel
authors: G
authors: G
authors: Gillessen-Kaesbach
authors: B
authors: B
authors: Horsthemke
mesh_terms: D000293:Adolescent; D000328:Adult; D000595:Amino Acid Sequence; D000886:Anthropometry; D001483:Base Sequence; D001827:Body Height; D002648:Child; D002675:Child, Preschool; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics*; D004252:DNA Mutational Analysis; D004268:DNA-Binding Proteins / Q000378:metabolism; D050981:Erythroid-Specific DNA-Binding Factors; D005091:Exons / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D007223:Infant; D017880:Limb Deformities, Congenital / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*; D010009:Osteochondrodysplasias / Q000145:classification* / Q000000981:diagnostic imaging / Q000235:genetics* / Q000473:pathology; D010375:Pedigree; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011859:Radiography; D013577:Syndrome; D014157:Transcription Factors / Q000378:metabolism; D016335:Zinc Fingers / Q000235:genetics
chemical_list: D004268:DNA-Binding Proteins; D050981:Erythroid-Specific DNA-Binding Factors; D014157:Transcription Factors