ACLS
- Known as:
- ACLS
- Catalog number:
- 001010A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACLS
Related genes to: ACLS
- Gene:
- ACLS NIH gene
- Name:
- acrocallosal syndrome
- Previous symbol:
- -
- Synonyms:
- -
- Chromosome:
- 12p13.3-p11.2
- Locus Type:
- phenotype only
- Date approved:
- 1993-01-19
- Date modifiied:
- 2015-08-10
- Gene:
- GLI3 NIH gene
- Name:
- GLI family zinc finger 3
- Previous symbol:
- GCPS, PHS
- Synonyms:
- PAP-A, PAPA, PAPA1, PAPB, ACLS, PPDIV
- Chromosome:
- 7p14.1
- Locus Type:
- gene with protein product
- Date approved:
- 1989-05-29
- Date modifiied:
- 2016-10-05
Related products to: ACLS
Related articles to: ACLS
- Acrocallosal syndrome (ACLS) is a rare genetic disorder characterized by agenesis or hypoplasia of corpus callosum (CC), polydactyly, craniofacial dysmorphism and severe intellectual deficiency. We previously identified KIF7, a key ciliary component of the Sonic hedgehog (SHH) pathway, as being a causative gene for this syndrome, thus including ACLS in the group of ciliopathies. In both humans and mice, KIF7 depletion leads to abnormal GLI3 processing and over-activation of SHH target genes. To understand the pathological mechanisms involved in CC defects in this syndrome, we took advantage of a previously described Kif7-/- mouse model to demonstrate that in addition to polydactyly and neural tube closure defects, these mice present CC agenesis with characteristic Probst bundles, thus recapitulating major ACLS features. We show that CC agenesis in these mice is associated with specific patterning defects of the cortical septum boundary leading to altered distribution of guidepost cells required to guide the callosal axons through the midline. Furthermore, by crossing Kif7-/- mice with Gli3Δ699 mice exclusively producing the repressive isoform of GLI3 (GLI3R), we demonstrate that decreased GLI3R signaling is fully responsible for the ACLS features in these mice, as all phenotypes are rescued by increasing GLI3R activity. Moreover, we show that increased FGF8 signaling is responsible in part for CC defects associated to KIF7 depletion, as modulating FGF8 signaling rescued CC formation anteriorly in Kif7-/- mice. Taken together our data demonstrate that ACLS features rely on defective GLI3R and FGF8 signaling. - Source: PubMed
Putoux AudreyBaas DominiquePaschaki MarieMorlé LauretteMaire CharlineAttié-Bitach TaniaThomas SophieDurand Bénédicte - We report on the novel association of trigonocephaly and polysyndactyly in two unrelated patients due to mutations within the last third (exon 14) and first third (exon 6) of the GLI3 gene, respectively. GLI3 acts as a downstream mediator of the Sonic hedgehog signal-transduction pathway which is essential for early development; and plays a role in cell growth, specialization, and patterning of structures such as the brain and limbs. GLI3 mutations have been identified in patients with Pallister-Hall, Grieg cephalopolysyndactyly syndrome (GCPS), postaxial polydactyly type A1, preaxial polydactyly type IV, and in one patient with acrocallosal syndrome (ACLS). Furthermore, deletions including the GLI3 gene have been reported in patients with features of GCPS and ACLS. To date, trigonocephaly has not been associated with abnormalities of GLI3 and craniosynostosis is not a feature of GCPS. However, Hootnick and Holmes reported on a father with polysyndactyly and son with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum, considered GCPS thereafter. Guzzetta et al. subsequently described a patient with trigonocephaly, polysyndactyly, and agenesis of the corpus callosum postulating a diagnosis of GCPS, later considered ACLS. In retrospect, these two patients, evaluated prior to mutational analysis, and our patients, with confirmed mutations, likely fall within the GLI3 morphopathy spectrum and may provide a bridge to better understanding those patients with overlapping features of GCPS and ACLS. Based on this observation, we suggest GLI3 studies in patients presenting with this constellation of findings, specifically metopic craniosynostosis with polysyndactyly, in order to provide appropriate medical management and genetic counseling. - Source: PubMed
McDonald-McGinn Donna MFeret HollyNah Hyun-DuckBartlett Scott PWhitaker Linton AZackai Elaine H - Greig cephalopolysyndactyly syndrome (GCPS) is caused by haploinsufficiency of GLI3 on 7p13. Features of GCPS include polydactyly, macrocephaly, and hypertelorism, and may be associated with cognitive deficits and abnormalities of the corpus callosum. GLI3 mutations in GCPS patients include point, frameshift, translocation, and gross deletion mutations. FISH and STRP analyses were applied to 34 patients with characteristics of GCPS. Deletions were identified in 11 patients and the extent of their deletion was determined. Nine patients with deletions had mental retardation (MR) or developmental delay (DD) and were classified as severe GCPS. These severe GCPS patients have manifestations that overlap with the acrocallosal syndrome (ACLS). The deletion breakpoints were analyzed in six patients whose deletions ranged in size from 151 kb to 10.6 Mb. Junction fragments were found to be distinct with no common sequences flanking the breakpoints. We conclude that patients with GCPS caused by large deletions that include GLI3 are likely to have cognitive deficits, and we hypothesize that this severe GCPS phenotype is caused by deletion of contiguous genes. - Source: PubMed
Johnston Jennifer JOlivos-Glander IsabelleTurner JoyceAleck KyrieckosBird Lynne MMehta LakshmiSchimke R NeilHeilstedt HeidiSpence J EdwardBlancato JanBiesecker Leslie G