GPC3 mutation/deletion and Simpson-Golbai-Behmel syndrome (SGBS). This syndrome is characterized by pre- and post- macrosomia and distinctive craniofacial features such as macrocephaly, coarse facial features, and palatal abnormalities. Mild-to-severe intellectual disability with or without structural brain anomalies are also commonly noted. Other variable findings include supernumerary nipples, diastasis recti, congenital heart defects, diaphragmatic hernia, and gastrointestinal anomalies. Affected individuals are at increased risk for embryonal tumors, mainly Wilms tumor. SGBS is caused by a loss-of-function mutation in the GPC3 gene, mapped in Xq26.2, causing for hyperactivation signaling of Wnt growth factors and Hedgehog signaling, which possibly correlates to the overgrowth and increased tumor risk seen in patients. The condition is considered to be a Mendelian disease, following an X-linked pattern of inheritance. In literature, there have been more than 80 mutations identified in SGBS, mostly point mutations. Watanabe et al. introduces a novel de-novo case featuring a 240 kb gene deletion, which includes a part of GPC3 and manifests endocrinological complications of precocious puberty and advanced bone aging not seen in previous SGBS patients. The 14.5-year-old Japanese boy presents intellectual disability, overgrowth, macrocephaly, dysmorphic facial features, and supernumerary nipples. During his early childhood, the boy grew to a tall stature, and showed overgrowth and advanced pubertal onset at age 11.5. Endocrine levels were then evaluated, presenting high levels of luteinizing hormone, follicular stimulating hormone, and insulin-like growth factor 1. His testicular volume was comparable to that of age 15. Bone age was assessed to also be equivalent to that of 15-year-old boy. The proband’s diagnosis of precocious puberty instigated whole-genome sequencing of both the parents and the patient. Results present the 240-kb deletion (ChrX: 132,624,991–132,865,393) including the GPC3 gene in the patient but not in the parents. This is the first SGBS case reported in which there are endocrinological complications and precious puberty. Although SGBS is mainly a disorder caused by point mutations, this report shows that deletions of Xq26.3 affecting the GPC3 gene also may cause this condition.
Watanabe et al. “Precocious puberty in a case of Simpson–Golabi–Behmel syndrome with a de novo 240-kb deletion including GPC3”. “Hum Genome Variation” 2022, v.9:23.
Chromosome Disorder Outreach Inc. medical geneticist and medical advisor Dr. Iosif Lurie M.D. Ph.D examines newly published research studies to locate the most important and relevant for our members. Synopses of these articles are then posted to our website’s research pages. For more information on any article please contact email@example.com