■戈林综合征是一种罕见的,常染色体显性遗传的多系统疾病,易发生癌症,如髓母细胞瘤和卵圆形基底细胞癌。PTCH1中的杂合致病变异是Gorlin综合征病例的90%的原因。PTCH1中的致病变异导致声波刺猬信号通路的过度刺激,在胚胎结构的发育和肿瘤发生中起作用。已经确定了Gorlin综合征的临床主要和次要诊断标准。牙源性角化囊肿(OKC)是Gorlin综合征入院的最常见原因。在这篇文章中,旨在提请注意Gorlin综合征患者在我国并不十分罕见,表型和畸形表现的变异性可能是诊断的线索。
■通过使用用于Illumina的IonAmpriseq外显子组RDY试剂盒,在IlluminaNextSeq550系统平台上进行外显子组测序。相应地对两个家庭中的其他受影响的个体进行Sanger测序。
■在这项研究中,介绍了来自三个无关家庭的9名Gorlin综合征患者的临床和分子检查结果。大头畸形,大脑镰状钙化,掌-足底坑,肋骨异常,在超过一半的患者中,OKC的检测顺序递减。检测到家族1中的一种新的杂合移码PTCH1变体,家族2中先前报道的无义PTCH1变体和家族3中的一种新的杂合剪接位点PTCH1变体。
■对于患有大头畸形的患者,应牢记Gorlin综合征,掌足底坑,OKC历史对所有家庭成员进行仔细检查对于及时诊断其他具有轻微表型发现的受影响个体至关重要。
UNASSIGNED: Gorlin syndrome is a rare, autosomal dominant multi-systemic disorder with a predisposition to the development of cancers such as medulloblastoma and nevoid basal cell carcinoma. Heterozygous pathogenic variants in PTCH1 are responsible for 90% of Gorlin syndrome cases. Pathogenic variants in PTCH1 cause overstimulation of the sonic hedgehog signaling pathway, which plays a role in the development of embryonic structures and tumorigenesis. Clinical major and minor diagnostic criteria for Gorlin syndrome have been determined. Odontogenic keratocyst (OKC) is the most common reason for medical admission in Gorlin syndrome. In this article, it is aimed to draw attention to the fact that patients with Gorlin syndrome are not very rare in our country and the variability in phenotypic and dysmorphic findings may be a clue for the diagnosis.
UNASSIGNED: Exome sequencing was performed on the Illumina NextSeq550 System platform by using the Ion Ampliseq exome RDY kit for Illumina. Sanger sequencing was performed accordingly for the other affected individuals in both families.
UNASSIGNED: In this study, the clinical and molecular findings of 9 Gorlin syndrome patients from three unrelated families are presented. Macrocephaly, calcification of falx cerebri, palmar-plantar pits, rib anomalies, and OKC were detected in decreasing order in more than half of the patients. A novel heterozygous frameshift PTCH1 variant in family 1, a nonsense previously reported PTCH1 variant in family 2, and a novel heterozygous splice-site PTCH1 variant in family 3 were detected.
UNASSIGNED: Gorlin syndrome should be kept in mind in patients presenting with macrocephaly, palmoplantar pits, and OKC history. Careful examination of all family members is essential in the timely diagnosis of other affected individuals with minor phenotypic findings.