[email protected] (受疫情影响,东南亚目前只开放曼谷诊所)
全周 (9AM - 5PM)

我们和你在一起

Extra info thumb
  • 总部: 泰国曼谷市巴吞汪区仑披尼分区 普勒吉路齐隆巷5号.
  • [email protected]
TREACHER COLLINS SYNDROME 2; TCS2

TREACHER COLLINS SYNDROME 2; TCS2

Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colo...

Treacher Collins syndrome is a disorder of craniofacial development characterized by a combination of bilateral downward slanting of the palpebral fissures, colobomas of the lower eyelids with a paucity of eyelashes medial to the defect, hypoplasia of the facial bones, cleft palate, malformation of the external ears, atresia of the external auditory canals, and bilateral conductive hearing loss (Dauwerse et al., 2011).

For additional phenotypic information and a discussion of genetic heterogeneity of Treacher Collins syndrome, see TCS1 (154500).

▼ Clinical Features
Vincent et al. (2016) reported the clinical features of the 7 patients they identified with POLR1D mutations causing TCS2. Six of the 7 had downward slanting palpebral fissures and/or malar hypoplasia, 5 had conductive deafness, and all 7 had mandibular hypoplasia. Between 40% and 60% of this small group had atresia of the external ear canal, coloboma of the lower eyelid, facial asymmetry, or projection of scalp hair on the lateral cheek. One in 6 patients examined had cleft palate, and 1 in 6 had a spinal malformation. None had any of the rare features reported in TCS1. Whether this was an effect of sample size or was due to the molecular basis was unknown.

▼ Inheritance
Treacher Collins syndrome-2 is an autosomal dominant disorder (Dauwerse et al., 2011).

Schaefer et al. (2014) reported 2 unrelated consanguineous Turkish families in which Treacher Collins syndrome-2 was inherited in an autosomal recessive pattern.

▼ Molecular Genetics
In a 3-year-old boy with Treacher Collins syndrome who was negative for mutation in the TCOF1 gene (606847), Dauwerse et al. (2011) performed genomewide copy number analysis and identified a 156-kb de novo deletion at chromosome 13q12.2 that encompassed the entire POLR1D gene (613715) and exon 1 of the LNX2 gene (609733). Sequence analysis of POLR1D and LNX2 in 10 additional Treacher Collins patients who were negative for mutations in TCOF1 revealed a boy who was heterozygous for a nonsense mutation in POLR1D (R87X; 613715.0001). Analysis of POLR1D in a further 242 individuals with typical TCS or with clinical findings in the TCS phenotypic spectrum who were negative for TCOF1 mutations yielded 10 heterozygous nonsense mutations and 7 heterozygous missense mutations in 20 index cases (see, e.g., 613715.0002-613715.0006).

Schaefer et al. (2014) reported 4 affected children from 2 unrelated consanguineous families with mild Treacher Collins syndrome (TCS2; 613717) who shared the same homozygous missense mutation in the POLR1D gene (L55V; 613715.0007). Both sets of unaffected parents and the unaffected sister of the first proband were heterozygous for the mutation. functional analysis of TCOF1 by real-time quantitative RT-PCR demonstrated a 50% reduction in transcripts, compatible with the hypothesis that this mutation impairs RNA polymerase and results in a lower amount of mature dimeric ribosomes.

Tags: 13q12.2

相关文章

TREACHER COLLINS SYNDROME 2; TCS2
FMS样酪氨酸激酶3

生长因子受体酪氨酸激酶家族包括几个具有不同结构特征的类别。...

TREACHER COLLINS SYNDROME 2; TCS2
基本转录因子IIIA

在真核生物中确定的第一个转录因子是来自西诺普斯·莱维斯(恩...

遇到问题了吗?