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High mutation detection rate in TCOF1 among Treacher Collins syndrome patients reveals clustering of mutations and 16 novel pathogenic changes
Author(s) -
Splendore Alessandra,
Silva Elias O.,
Alonso Luís G.,
RichieriCosta Antônio,
Alonso Nivaldo,
Rosa Alberto,
Carakushanky Gerson,
Cavalcanti Denise P.,
Brui Décio,
PassosBueno Maria Rita
Publication year - 2000
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/1098-1004(200010)16:4<315::aid-humu4>3.0.co;2-h
Subject(s) - biology , treacher collins syndrome , genetics , single nucleotide polymorphism , coding region , mutation rate , genotype , mutation , gene , exon , single strand conformation polymorphism , dna sequencing , craniofacial
Twenty‐eight families with a clinical diagnosis of Treacher Collins syndrome were screened for mutations in the 25 coding exons of TCOF1 and their adjacent splice junctions through SSCP and direct sequencing. Pathogenic mutations were detected in 26 patients, yielding the highest detection rate reported so far for this disease (93%) and bringing the number of known disease‐causing mutations from 35 to 51. This is the first report to describe clustering of pathogenic mutations. Thirteen novel polymorphic alterations were characterized, confirming previous reports that TCOF1 has an unusually high rate of single‐nucleotide polymorphisms (SNPs) within its coding region. We suggest a possible different mechanism leading to TCS or genetic heterogeneity for this condition, as we identified two families with no apparent pathogenic mutation in the gene. Furthermore, our data confirm the absence of genotype–phenotype correlation and reinforce that the apparent anticipation often observed in TCS families is due to ascertainment bias. Hum Mutat 16:315–322, 2000. © 2000 Wiley‐Liss, Inc.