Clinical Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Medical Molecular Genetics Department, Human Genetics and Genome Research Institute, National Research Centre, Cairo, Egypt.
Congenit Anom (Kyoto). 2022 Mar;62(2):68-77. doi: 10.1111/cga.12457. Epub 2022 Jan 3.
Mutations in the PORCN gene cause an X-linked dominant condition; focal dermal hypoplasia (FDH), characterized by atrophic skin, pigmented skin lesions in addition to several ocular and skeletal malformations. FDH is rare with around 275 cases reported so far from diverse ethnic groups. Herein, we provide a report of two new patients with FDH from Egypt. In addition to the typical clinical manifestations of the disease, infrequently reported clinical findings in the form of broad metaphysis, bilateral short broad femurs, and dermal sinus over the sacrum were seen in Patient 1 and partial fusion of labia majora, ventral hernia, and bladder extrophy were present in Patient 2. Two heterozygous protein-truncating PORCN mutations were identified in our patients, a known nonsense c.370C>T p.(Arg124Ter) and a novel frameshift c.375delG p.(Ala126HisfsTer3). Segregation analyses confirmed that the two mutations were "de novo" and not inherited from any of the parents. Our study expands the clinical and mutational spectrum of focal dermal hypoplasia and emphasizes the importance of investigating the different body systems and organs for the early management of patients.
PORCN 基因突变导致 X 连锁显性遗传疾病；局灶性皮肤发育不良（FDH），其特征是皮肤萎缩，皮肤色素沉着病变，此外还有多种眼部和骨骼畸形。FDH 较为罕见，迄今为止，来自不同种族的报告约有 275 例。在此，我们报告了来自埃及的两名 FDH 新患者。除了该病的典型临床表现外，患者 1 还出现了不常见的临床表现，包括宽干骺端、双侧短而宽的股骨和骶骨皮窦；患者 2 则存在大阴唇部分融合、腹疝和膀胱外翻。我们在这两名患者中发现了两种杂合的蛋白截断 PORCN 突变，一种是已知的无义突变 c.370C>T p.(Arg124Ter)，另一种是新的移码突变 c.375delG p.(Ala126HisfsTer3)。家系分析证实这两种突变是“新生突变”，而非来自父母的任何一方遗传。本研究扩展了 FDH 的临床和突变谱，并强调了对不同系统和器官进行调查以早期管理患者的重要性。
