PDF(Pubmed)
Abstract：
UNASSIGNED: Birk-Barel syndrome, also known as KCNK9 imprinting syndrome, is a rare fertility disorder. And the main clinical manifestations include congenital hypotonic, craniofacial malformation, developmental delay, and intellectual disability. Generally, such patients could be diagnosed beyond the infant period. Moreover, the delayed diagnosis might lead to a poor prognosis of rehabilitation therapy. However, neonatal obstructive sleep apnea (OSA) was seldom reported in Birk-Barel syndrome. Here, we reported a severe neonatal OSA case induced by Birk-Barel syndrome, resulting in an early diagnosis with improved outcomes by integrative management.
UNASSIGNED: The proband was a neonate presenting with recurrent severe OSA, with craniofacial deformity and congenital muscle hypotonia. Bronchoscopy examinations indicated a negative finding of pharyngeal and bronchus stenosis, while laryngomalacia had been observed. Whole exon sequencing demonstrated a c. 710C>A heterozygous variant resulting in a change of amino acid (p.A237D). This variant resulted in a change of amino acid sequence, affected protein features and changed splice site leading to a structural deformation in KCNK9 protein. This p.A237D variant also affected the crystal structure on the p.G129 site. Additionally, we used the mSCM tool to measure the free energy changes between wild-type and mutant protein, which indicated highly destabilizing (-2.622 kcal/mol).
UNASSIGNED: This case report expands the understanding of Birk-Barel syndrome and indicates that OSA could serve as the on-set manifestation of Birk-Barel syndrome. This case emphasized genetic variants which were associated with severe neonatal OSA. Adequate WES assessment promotes early intervention and improves the prognosis of neurological disorders in young children.
UNASSIGNED: The proband was a neonate presenting with recurrent severe OSA, with craniofacial deformity and congenital muscle hypotonia. Bronchoscopy examinations indicated a negative finding of pharyngeal and bronchus stenosis, while laryngomalacia had been observed. Whole exon sequencing demonstrated a c. 710C>A heterozygous variant resulting in a change of amino acid (p.A237D). This variant resulted in a change of amino acid sequence, affected protein features and changed splice site leading to a structural deformation in KCNK9 protein. This p.A237D variant also affected the crystal structure on the p.G129 site. Additionally, we used the mSCM tool to measure the free energy changes between wild-type and mutant protein, which indicated highly destabilizing (-2.622 kcal/mol).
UNASSIGNED: This case report expands the understanding of Birk-Barel syndrome and indicates that OSA could serve as the on-set manifestation of Birk-Barel syndrome. This case emphasized genetic variants which were associated with severe neonatal OSA. Adequate WES assessment promotes early intervention and improves the prognosis of neurological disorders in young children.
摘要：
■Birk-Barel综合征,也被称为KCNK9印记综合征，是一种罕见的生育障碍.主要临床表现为先天性低张,颅面畸形,发育迟缓,智力残疾。一般来说,这样的病人可以诊断超过婴儿时期。此外，延迟诊断可能导致康复治疗的预后不良。然而,新生儿阻塞性睡眠呼吸暂停(OSA)在Birk-Barel综合征中很少报道.这里,我们报道了一例Birk-Barel综合征引起的严重新生儿OSA病例，通过综合管理，导致早期诊断，改善预后。
■先证者是一名新生儿，表现为复发性重度OSA，伴有颅面畸形和先天性肌张力减退。支气管镜检查提示咽部和支气管狭窄阴性，同时观察到喉软化。全外显子测序证明了c。710C>A杂合变体，导致氨基酸变化（p。A237D).这种变异导致了氨基酸序列的改变,影响蛋白特征和改变剪接位点导致KCNK9蛋白结构变形。该p.A237D变体还影响p.G129位点上的晶体结构。此外,我们使用mSCM工具来测量野生型和突变蛋白之间的自由能变化，这表明高度不稳定（-2.622kcal/mol）。
本病例报告扩大了对Birk-Barel综合征的认识，表明OSA可作为Birk-Barel综合征的首发表现。该病例强调了与严重新生儿OSA相关的遗传变异。充分的WES评估可促进早期干预并改善幼儿神经系统疾病的预后。
■先证者是一名新生儿，表现为复发性重度OSA，伴有颅面畸形和先天性肌张力减退。支气管镜检查提示咽部和支气管狭窄阴性，同时观察到喉软化。全外显子测序证明了c。710C>A杂合变体，导致氨基酸变化（p。A237D).这种变异导致了氨基酸序列的改变,影响蛋白特征和改变剪接位点导致KCNK9蛋白结构变形。该p.A237D变体还影响p.G129位点上的晶体结构。此外,我们使用mSCM工具来测量野生型和突变蛋白之间的自由能变化，这表明高度不稳定（-2.622kcal/mol）。
本病例报告扩大了对Birk-Barel综合征的认识，表明OSA可作为Birk-Barel综合征的首发表现。该病例强调了与严重新生儿OSA相关的遗传变异。充分的WES评估可促进早期干预并改善幼儿神经系统疾病的预后。
