MBTPS2 mutation causes BRESEK/BRESHECK syndrome

• Published in: American journal of medical genetics. Part A 2012-01, Vol.158A (1), p.97-102
• Main Authors: Naiki, Misako, Mizuno, Seiji, Yamada, Kenichiro, Yamada, Yasukazu, Kimura, Reiko, Oshiro, Makoto, Okamoto, Nobuhiko, Makita, Yoshio, Seishima, Mariko, Wakamatsu, Nobuaki
• Format: Article
• Language: English
• Subjects: Biological and medical sciences; Brain - abnormalities; BRESEK/BRESHECK syndrome; Congenital Abnormalities - diagnosis; Congenital Abnormalities - genetics; DNA Fragmentation; DNA Mutational Analysis; Ear - abnormalities; Ectodermal Dysplasia - complications; Ectodermal Dysplasia - diagnosis; Ectodermal Dysplasia - genetics; Genetic Diseases, X-Linked - complications; Genetic Diseases, X-Linked - diagnosis; Genetic Diseases, X-Linked - genetics; Genome-Wide Association Study; Growth Disorders - genetics; Hirschsprung Disease - complications; Hirschsprung Disease - diagnosis; Hirschsprung Disease - genetics; Humans; IFAP syndrome; Infant; Intellectual Disability - complications; Intellectual Disability - diagnosis; Intellectual Disability - genetics; Kidney - abnormalities; Male; MBTPS2; Medical genetics; Medical sciences; Metalloendopeptidases - genetics; Molecular Biology; Mutation; Pedigree; S2P
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.34373

BRESEK/BRESHECK syndrome is a multiple congenital malformation characterized by brain anomalies, intellectual disability, ectodermal dysplasia, skeletal deformities, ear or eye anomalies, and renal anomalies or small kidneys, with or without Hirschsprung disease and cleft palate or cryptorchidism. This syndrome has only been reported in three male patients. Here, we report on the fourth male patient presenting with brain anomaly, intellectual disability, growth retardation, ectodermal dysplasia, vertebral (skeletal) anomaly, Hirschsprung disease, low‐set and large ears, cryptorchidism, and small kidneys. These manifestations fulfill the clinical diagnostic criteria of BRESHECK syndrome. Since all patients with BRESEK/BRESHECK syndrome are male, and X‐linked syndrome of ichthyosis follicularis with atrichia and photophobia is sometimes associated with several features of BRESEK/BRESHECK syndrome such as intellectual disability, vertebral and renal anomalies, and Hirschsprung disease, we analyzed the causal gene of ichthyosis follicularis with atrichia and photophobia syndrome, MBTPS2, in the present patient and identified an p.Arg429His mutation. This mutation has been reported to cause the most severe type of ichthyosis follicularis with atrichia and photophobia syndrome, including neonatal and infantile death. These results demonstrate that the p.Arg429His mutation in MBTPS2 causes BRESEK/BRESHECK syndrome. © 2011 Wiley Periodicals, Inc.