Wang Qingming, Huang Xiaoling, Liu Yanhui, Peng Qian, Zhang Yuqiong, Liu Jianxin, Yuan Haiming
Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, China; Dongguan Institute of Reproductive and Genetic Research, Dongguan, 523120, China.
Dongguan Maternal and Child Health Care Hospital, Dongguan, 523120, China.
Eur J Med Genet. 2020 Jan;63(1):103611. doi: 10.1016/j.ejmg.2019.01.001. Epub 2019 Jan 4.
Xia-Gibbs syndrome is a rare genetic condition characterized by intellectual disability, growth retardation, delayed psychomotor development with absent or poor expressive language, distinctive facial features, hypotonia, laryngomalacia and obstructive sleep apnea. At present, Xia-Gibbs syndrome has been reported to be mainly caused by truncating mutations in AHDC1 gene located on chromosome 1p36.11. However, the evidence supporting AHDC1 deletion as a cause of this syndrome is still limited. Here we report an 8-year-old boy carrying a de novo 575 Kb microdeletion at 1p36.11 including AHDC1 gene. The boy is characterized by intellectual disability, developmental delay, short stature, expressive language delay, facial dysmorphism, obstructive sleep apnea and multiple congenital anomalies, which are mostly consistent with the characteristics of Xia-Gibbs syndrome. Therefore, we provide further supporting evidence that AHDC1 deletion causes Xia-Gibbs syndrome through a haploinsufficiency mechanism. Currently, clinical consequences of AHDC1 gene duplication has never been reported. Here, we identify a de novo 480 Kb duplication at 1p36.11p35.3 spanning the entire AHDC1 gene in a 2-year-8-month boy, who displays similar clinical features with that of Xia-Gibbs syndrome, in particular, expressive language delay, hypotonia, laryngomalacia and obstructive sleep apnea, as well as mirrored phenotypes such as overgrowth and advanced bone age. WES test excludes to the degree possible other known genetic causes. This case suggests that AHDC1 gene duplication may be clinical significance.
夏-吉布斯综合征是一种罕见的遗传性疾病，其特征为智力残疾、生长发育迟缓、精神运动发育延迟伴表达性语言缺失或发育不良、独特的面部特征、肌张力减退、喉软化和阻塞性睡眠呼吸暂停。目前，据报道夏-吉布斯综合征主要由位于1p36.11的AHDC1基因的截短突变引起。然而，支持AHDC1基因缺失作为该综合征病因的证据仍然有限。在此，我们报告一名8岁男孩，其在1p36.11处存在一个包含AHDC1基因的575 kb的新发微缺失。该男孩具有智力残疾、发育迟缓、身材矮小、表达性语言发育延迟、面部畸形、阻塞性睡眠呼吸暂停和多种先天性异常等特征，这些大多与夏-吉布斯综合征的特征相符。因此，我们提供了进一步的支持证据，表明AHDC1基因缺失通过单倍剂量不足机制导致夏-吉布斯综合征。目前，AHDC1基因重复的临床后果尚未见报道。在此，我们在一名2岁8个月大的男孩中鉴定出一个位于1p36.11p35.3的480 kb的新发重复，该重复跨越整个AHDC1基因，该男孩表现出与夏-吉布斯综合征相似的临床特征，特别是表达性语言发育延迟、肌张力减退、喉软化和阻塞性睡眠呼吸暂停，以及如过度生长和骨龄提前等镜像表型。全外显子组测序检测尽可能排除了其他已知的遗传病因。该病例提示AHDC1基因重复可能具有临床意义。
