Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

Hilton, Matthew J.; Sawyer, Jacob M.; Gutiérrez, Laura; Hogart, Amber; Kung, Ting C; Wells, Dan E.

doi:10.1007/s100380200010

Cited by 37 publications

(26 citation statements)

References 7 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition to EDNRB involved in skin and hair pigmentation, other genes such as TRSP1 which belonged to N and KRTAP8-1 which was not eligible for network analysis play a role in hair development in human and mouse. Indeed, TRPS1 is a zinc finger transcription factor implicated in growth and trichosis, some of its variants being associated with trichorhinophalangeal syndromes [54,55]. It is down-regulated in patients affected by hypertrichosis and in a mouse model of hypertrichosis [56].…”

Section: Resultsmentioning

confidence: 99%

A whole genome Bayesian scan for adaptive genetic divergence in West African cattle

et al. 2009

View full text Add to dashboard Cite

BackgroundThe recent settlement of cattle in West Africa after several waves of migration from remote centres of domestication has imposed dramatic changes in their environmental conditions, in particular through exposure to new pathogens. West African cattle populations thus represent an appealing model to unravel the genome response to adaptation to tropical conditions. The purpose of this study was to identify footprints of adaptive selection at the whole genome level in a newly collected data set comprising 36,320 SNPs genotyped in 9 West African cattle populations.ResultsAfter a detailed analysis of population structure, we performed a scan for SNP differentiation via a previously proposed Bayesian procedure including extensions to improve the detection of loci under selection. Based on these results we identified 53 genomic regions and 42 strong candidate genes. Their physiological functions were mainly related to immune response (MHC region which was found under strong balancing selection, CD79A, CXCR4, DLK1, RFX3, SEMA4A, TICAM1 and TRIM21), nervous system (NEUROD6, OLFM2, MAGI1, SEMA4A and HTR4) and skin and hair properties (EDNRB, TRSP1 and KRTAP8-1).ConclusionThe main possible underlying selective pressures may be related to climatic conditions but also to the host response to pathogens such as Trypanosoma(sp). Overall, these results might open the way towards the identification of important variants involved in adaptation to tropical conditions and in particular to resistance to tropical infectious diseases.

show abstract

Section: Resultsmentioning

confidence: 99%

A whole genome Bayesian scan for adaptive genetic divergence in West African cattle

et al. 2009

View full text Add to dashboard Cite

show abstract

“…TRPS is a condition inherited in an autosomal dominant manner [4]. Approximately, half of mutations reported in the literature were inherited while the other half represents de novo mutations [31, 32]. In our family, it was evident that the affected father had transmitted the missense mutation to his 3 children in autosomal dominant manner.…”

Section: Discussionmentioning

confidence: 75%

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report

et al. 2017

View full text Add to dashboard Cite

BackgroundTricho-rhino-phalangeal syndrome (TRPS) is an autosomal dominant disorder characterized by craniofacial and skeletal malformations including short stature, thin scalp hair, sparse lateral eyebrows, pear-shaped nose and cone shaped epiphyses. This condition is caused by haploinsufficiency of the TRPS1 gene. Previous genotype-phenotype studies have correlated exon 6 missense mutations with TRPS type III, a severe form of type I with pronounced, facial characteristics, short stature and brachydactyly and differing from type II by the absence of exostoses and mental retardation.Case presentationWe report the first case of a Moroccan family, a father and his three children, in which the diagnosis of type III TRPS was suspected based on severe clinical and radiological features. Molecular analysis of the TRPS1 gene revealed a novel missense mutation in exon 6, (p.Ala932Ser), located in the GATA-type DNA-binding zinc finger domain.ConclusionOur observations in this kindred support the previous genotype-phenotype results suggesting that patients with more pronounced facial characteristics and more severe shortening of hands and feet are more likely to have mutation in exon 6 of TRPS1.

show abstract

“…TRPS patients generally present slow-growing and sparse scalp hair, medially thick and laterally thin eyebrows, a bulbous pear-shaped nose, a long flat philtrum, a thin upper vermilion border, large protruding ears [2], and bone abnormalities including mild to severe brachydactyly, cone-shaped epiphyses, hip dysplasia and short stature [2]. Malformations of inner organs have also been reported [3].…”

Section: Introductionmentioning

confidence: 99%

“…TRPS II is phenotypically distinguished from TRPS I by the presence of multiple cartilaginous exostoses and other less frequent features, such as intellectual disability, lax skin and a tendency toward bone fractures. Finally, TRPS III (OMIM 190351) is the result of missense mutations in the region of TRPS1 that encodes a GATA-type zinc finger domain [2,6,10]. The primary clinical difference between TRPS I and TRPS III is in the severity of the skeletal abnormalities, especially brachydactyly and short stature [11].…”

Section: Introductionmentioning

confidence: 99%

New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene

et al. 2014

View full text Add to dashboard Cite

BackgroundTrichorhinophalangeal syndrome (TRPS) is a rare autosomal dominant genetic disorder characterised by distinctive craniofacial and skeletal abnormalities. TRPS is generally associated with mutations in the TRPS1 gene at 8q23.3 or microdeletions of the 8q23.3-q24.11 region. However, three deletions affecting the same chromosome region and a familial translocation t(8;13) co-segregating with TRPS, which do not encompass or disrupt the TRPS1 gene, have been reported. A deregulated expression of TRPS1 has been hypothesised as cause of the TRPS phenotype of these patients.Case presentationWe report the clinical and molecular characterisation of a 57-year-old Caucasian woman carrying the t(2;8)(p16.1;q23.3) de novo balanced translocation. The proband presented with peculiar clinical features (severe craniofacial dysmorphism, alopecia universalis, severe scoliosis, mitral valve prolapse, mild mental impairment and normal growth parameters) that partially overlap with TRPS I. Mutational and array CGH analyses ruled out any genetic defect affecting TRPS1 or genomic alteration at the translocation breakpoint or elsewhere in the genome. Breakpoint mapping excluded disruption of TRPS1, and revealed that the chromosome 8q23.3 breakpoint was located within the IVS10 of the long intergenic non-coding RNA LINC00536, at approximately 300 kb from the TRPS1 5’ end. Conversely, the 2p16.1 breakpoint mapped within a LINE sequence, in a region that lacks transcriptional regulatory elements. As a result of the translocation, nucleotide base pair additions and deletions were detected at both breakpoint junction fragments, and an evolutionarily conserved VISTA enhancer element from 2p16.1 was relocated at approximately 325 kb from the TRPS1 promoter.ConclusionsWe suggest that the disruption of the genomic architecture of cis regulatory elements downstream the TRPS1 5′ region, combined with the translocation of a novel enhancer element nearby TRPS1, might be the pathogenetic mechanism underpinning the proband’s phenotype. The clinical and genetic characterisation of the present subject allowed us to make a genetic diagnosis in the context of a known syndrome, contributing to a better comprehension of the complex transcriptional regulation of TRPS1 and TRPS ethiopathogenesis.

show abstract

Analysis of novel and recurrent mutations responsible for the tricho-rhino-phalangeal syndromes

Cited by 37 publications

References 7 publications

A whole genome Bayesian scan for adaptive genetic divergence in West African cattle

A whole genome Bayesian scan for adaptive genetic divergence in West African cattle

A novel TRPS1 mutation in a Moroccan family with Tricho-rhino-phalangeal syndrome type III: case report

New case of trichorinophalangeal syndrome-like phenotype with a de novo t(2;8)(p16.1;q23.3) translocation which does not disrupt the TRPS1 gene

Contact Info

Product

Resources

About