3 research outputs found
Q289P mutation in FGFR2 gene causes Saethre-Chotzen syndrome: Some considerations about familial heterogeneity
Objective: To describe the first report on a three-generation family presenting typical features of Saethre-Chotzen syndrome, in which the Q289P mutation in the FGFR2 gene was detected. Design: Dysmorphological evaluation was performed by a clinical geneticist. Direct sequencing of the polymerase chain reaction-amplified coding region of TWIST and screening for the P250R mutation in the FGFR3 gene were performed. Exons IIIa and IIIc of FGFR2 were sequenced also. The mutation was confirmed by both restriction-enzyme digestion and allelic-specific polymerase chain reaction. Results: Neither TWIST gene analysis nor analysis of the P250R mutation on gene FGFR3 showed mutation within the coding sequence. A nucleotide change from CAG to CCG in exon Ilia of the FGFR2 gene that caused a Q289P mutation was detected, although exon IIIc in the propositus was normal. These same results were detected in his mother, but no other members of the kindred presented clinical features consistent with Saethre-Chotzen syndrome. Conclusions: This mutation was previously reported in individuals with Crouzon and Jackson-Weiss syndromes. The FGFR2 mutation in the family with Saethre-Chotzen syndrome herein reported reinforces the idea of an interaction among TWIST and FGFR genes during development. Absence of the Q289P mutation in some affected individuals in this family is discussed.43214214
Clinical findings in four Brazilian families affected by Saethre-Chotzen syndrome without TWIST mutations
Objective: To analyze the dysmorphological variability and to investigate the presence of mutations in the exon 1 of TWIST gene using direct sequencing in Brazilian families presenting with Saethre-Chotzen Syndrome (SCS). Methods: Four families with 24 patients diagnosed as having features of SCS were studied. Phenotypic characteristics of all patients were inventoried. The investigation protocol included anamnesis, dysmorphological examination, abdominal ultrasound, spine and cranium x-ray, chromosomal analysis on GTG banding, and screening for mutations in the exon 1 of TWIST gene. Results: Frequent facial features included brachycephaly (24 of 24), facial asymmetry (20 of 24), prominent ears crus (15 of 24), low-set ears (14 of 24), maxillary hypoplasia (13 of 24), prominent nasal bridge (13 of 24), ptosis of the eyelids (12 of 24), and low-set frontal hairline (12 of 24). Limb abnormalities such as partial hand cutaneous syndactyly (18 of 24), clinodactyly (13 of 24), and broad great toes (13 of 24), and partial cutaneous syndactyly of the feet (9 of 24) were also detected. Among radiological findings were relevant bicoronal (eight of nine) and unicoronal (one of nine) craniosynostosis, digital impressions (eight of nine), bilateral parietal foramina (two of nine), partial fusion 1 and 2 degrees costal arches (two of nine) and bifid spine on lumbar vertebra (two of nine). GTG-banding chromosomal analyses were normal. No TWIST gene mutations were found. Conclusions: Affected individuals in these four SCS families may carry mutations in other genes of the same developmental pathway. Considering the complexity of the genes involved in skull-limbs development, an accurate dysmorphological evaluation in patients with SCS and their families is especially important for genetic counseling.41325025