背景:KIAA0586变种与短肋骨胸部发育不良有关,以狭窄的胸部为特征的常染色体隐性骨骼纤毛病,四肢短,和放射性骨骼异常。
方法:患者1和2是两个出现胸部发育不良和口腔异常的罗马吉普赛兄弟姐妹。
方法:自定义NGS基因面板,包括与骨骼纤毛病相关的基因,鉴定了纯合KIAA0586剪接变体c.1815G>A(p。Gln605Gln)在两个兄弟姐妹中,证实短肋骨多指的临床诊断。
方法:患者被转移到新生儿重症监护病房并接受生命支持治疗。
结果:患者1和2在出生几小时和一个月后死亡,分别,因为呼吸衰竭与疾病有关。
结论:我们报告了两名患者,这些患者患有短肋骨多指综合征和与KIAA0586中的c.1815G>A变异相关的口腔-面部-数字综合征重叠表型,提示一种非常特殊的基因型-表型相关性。
BACKGROUND: KIAA0586 variants have been associated to short-rib thoracic dysplasia, an autosomal recessive skeletal ciliopathy characterized by a narrow thorax, short limbs, and radiological skeletal abnormalities.
METHODS: Patients 1 and 2 were two Roma Gypsy siblings presenting thoracic dysplasia and a combination of oral cavity anomalies.
METHODS: A custom NGS gene panel, including genes associated to skeletal ciliopathies, identified the homozygous KIAA0586 splicing variant c.1815G>A (p.Gln605Gln) in both siblings, confirming the clinical diagnosis of short-rib-polydactyly.
METHODS: Patients were transferred to neonatal intensive care unit and received life-support treatment.
RESULTS: Patients 1 and 2 died after few hours and 1 month of birth, respectively, because of respiratory failure related with the disease.
CONCLUSIONS: We report two patients affected by short-rib polydactyly syndrome and overlapping phenotype with oral-facial-digital syndrome associated with the c.1815G>A variant in KIAA0586, suggesting a quite peculiar genotype-phenotype correlation.