背景:外胚层发育不良是一组>200种临床和先天性异质性疾病,其特征是外胚层结构发育异常,比如头发,指甲,牙齿,和汗腺。我们在这里报告了五个不同类型的外胚层发育不良(ED)的希腊家庭的临床和分子遗传分析。
方法:该研究涉及来自5个希腊家庭的15个人,其中包括8名ED患者,5个隐性X连锁或常染色体ED的携带者,2个健康的亲戚经过遗传咨询,父母在随后的基因检测前签署了知情同意书.
方法:从所有研究个体的白细胞中分离基因组DNA。使用下一代测序(NGS)基因组对患者DNA样本进行突变搜索,全外显子组测序(WES),染色体微阵列分析(CMA),和多重连接依赖性探针扩增(MLPA)技术。
结果:在5例婴儿和恒牙部分无牙齿的男性患者中,怀疑临床诊断为常见的X连锁隐性多汗性外胚层发育不良(HED),多汗症,来自三个家庭的稀疏头发。所有HED患者均为EDA1基因缺失的半合子(Xq13.1):三名相关患者有20bp缺失,一个有19个bp的缺失,其中一个有180bp的缺失。1例女性患者因TP63基因(3q28)的杂合错义突变而出现了罕见的常染色体显性遗传综合征,即不孕症-外胚层发育不良-唇腭裂(AEC)。两个兄弟姐妹患有少毛症和低度症,一个女性和一个男性,在TSPEAR基因(21q22.3)的复合杂合性中具有两个致病性突变;因此,他们表现为14型外胚层发育不良(ECTD14)。
结论:临床和分子遗传学分析可以准确诊断不同类型的ED。在报告的家庭中,遗传诊断和遗传咨询帮助父母真实地观察孩子的病情,并与专家合作,他们将为孩子提供最好的治疗。
BACKGROUND: Ectodermal dysplasias are a group of >200 clinically and congenitally heterogeneous disorders characterized by abnormal development in the ectodermal structures, such as hair, nails, teeth, and sweat glands. We report here the clinical and molecular genetic analysis of five Greek families with different types of ectodermal dysplasia (ED).
METHODS: The study involved 15 individuals from 5 Greek families that included 8 ED patients, 5 carriers of recessive X-linked or autosomal ED, and 2 healthy relatives. After genetic counseling, the parents signed an informed consent form before subsequent genetic testing.
METHODS: Genomic DNA was isolated from white blood cells of all studied individuals. The search for mutations was realized in patients\' DNA samples using next-generation sequencing (NGS) gene panel, whole exome sequencing (WES), chromosomal microarray analysis (CMA), and multiplex ligation-dependent probe amplification (MLPA) technique.
RESULTS: The clinical diagnosis of common X-linked recessive hypohidrotic ectodermal dysplasia (HED) was suspected in five male patients with partial anodontia of baby and permanent teeth, hypohidrosis, and thin hair from three families. All HED patients were hemizygous for deletions in the
EDA1 gene (Xq13.1): three related patients had a 20 bp deletion, one had a 19 bp deletion, and one had a 180 bp deletion. A female patient had the rare autosomal dominant syndrome of ankyloblepharon-ectodermal dysplasia-cleft lip/palate (AEC) caused by heterozygous missense mutation in the TP63 gene (3q28) that appeared de novo. Two siblings with hypotrichosis and hypodontia, a female and a male, had two pathogenic mutations in compound heterozygosity in the TSPEAR gene (21q22.3); therefore they presented with ectodermal dysplasia type 14 (ECTD14).
CONCLUSIONS: Clinical and molecular genetic analysis may set an accurate diagnosis of different types of ED. In the reported families, genetic diagnosis and genetic counselling assisted the parents to view their children\'s condition realistically and to cooperate with the specialists who will contribute to the best possible treatment for their children.