A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia
A novel gene (FAM20B encoding glycosaminoglycan xylosylkinase) for neonatal short limb dysplasia resembling Desbuquois dysplasia
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DOI：
10.1111/cge.13530
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发表时间：
2019-06-01
影响因子：
3.5
通讯作者：
Kurosawa, Kenji
中科院分区：
文献类型：
--
作者：
Kuroda, Yukiko;Murakami, Hiroaki;Kurosawa, Kenji
Desbuquois发育不良（DBQD）是一种常染色体隐性遗传异质性疾病，其特征是关节松弛和骨骼变化，包括股骨独特的猴扳手外观，晚期腕骨骨化和前轴趾异常模式。已经报道了DBQD的两个基因（CANT 1编码钙激活核苷酸酶-1和XYLT 1编码木糖基转移酶-1）。我们提出了一个新的基因，新生儿短肢发育不良类似DBQD，基于两个受影响的兄弟姐妹的表型和基因型。受影响的男孩和女孩分别在婴儿早期和出生后不久死亡。临床特征包括面中部发育不全、胸部发育不全伴呼吸衰竭、身材非常矮小（约为出生身长的-7 SD）伴四肢中肢缩短和大关节多发性脱位。放射学检查显示小转子突出，长骨干骺端外展，关节脱位。受影响的男孩有轴前手指发育不全，受影响的女孩表现出重叠和并趾的轴前手指。对该女孩的分子分析显示FAM 20 B中存在复合杂合变体（NM_014864：c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4）。FAM 20 B编码糖胺聚糖木糖基激酶，其作用于木糖基转移酶-1的下游。鉴于FAM 20 B缺陷导致小鼠和斑马鱼的骨骼表型，这些变体极有可能是致病性的。
Desbuquois dysplasia (DBQD) is an autosomal recessive heterogeneous disorder characterized by joint laxity and skeletal changes, including a distinctive monkey-wrench appearance of the femora, advanced carpal ossification, and abnormal patterning of the preaxial digits. Two genes for DBQD (CANT1 encoding calcium-activated nucleotidase-1 and XYLT1 encoding xylosyltransferase-1) have been reported. We propose a novel gene for neonatal short limb dysplasia resembling DBQD, based on the phenotype and genotype of two affected siblings. The affected boy and girl died in early infancy and shortly after birth, respectively. The clinical hallmarks included mid-face hypoplasia, thoracic hypoplasia with respiratory failure, very short stature (approximately -7 SD of birth length) with mesomelic shortening of the limbs, and multiple dislocations of the large joints. Radiological examinations showed prominent lesser trochanter, flared metaphyses of the long bones, and joint dislocations. The affected boy had preaxial digital hypoplasia, and the affected girl showed overlapping and syndactyly of the preaxial digits. Molecular analyses of the girl showed compound heterozygous variants in FAM20B (NM_014864: c.174_178delTACCT p.T59Afs*19/c.1038delG p.N347Mfs*4). FAM20B encodes glycosaminoglycan xylosylkinase, which acts downstream of xylosyltransferase-1. Given the fact that FAM20B deficiency causes skeletal phenotypes in mice and zebrafish, these variants are highly probable to be pathogenic.