Jiao Xue1, Hui Li1, Yuehua Zhang1, Zhixian Yang2. 1. Department of Pediatrics, Peking University First Hospital, Beijing, China. 2. Department of Pediatrics, Peking University First Hospital, Beijing, China. Electronic address: zhixian.yang@163.com.
Abstract
OBJECTIVE: Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome. METHODS: The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined. RESULTS: Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysis anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys) of PIGV in patient 1, and c.458T>C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR). CONCLUSION: To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome.
OBJECTIVE:Hyperphosphatasia mental retardation syndrome (Mabry syndrome) is an autosomal recessive disorder. We aim to analyze two Chinese patients diagnosed as Mabry syndrome. METHODS: The clinical manifestations, diagnosis and treatment were observed in two patients. Genetic analysis including PIGV and PIGO was examined. RESULTS: Two patients were diagnosed as Mabry syndrome clinically and genetically. Developmental delay, hyperphosphatasia and seizures were presented in both of them. Typical facial dysmorphism and hypoplastic terminal phalanges were only found in one. Some novel presentations including congenital laryngeal cartilage softening, inguinal hernia, broken palmprint, optic atrophy and skeleton dysplasia such as carpal age delay and metaphysis anomalies were observed in two patients. Molecular genetic analysis revealed compound heterozygous mutations of PIGV or PIGO in our patients, including c.615C>G (p.Asn205Lys) and c.854A>G (p.Tyr285Cys) of PIGV in patient 1, and c.458T>C (p.Phe153Ser) and c.1355_1356del (p.Ala452Glyfs*52) of PIGO in patient 2. Additionally, a heterozygous c.2926G>A (Asp976Asn) of PCDH19 was identified in patient with PIGV mutations, the causative gene of Epilepsy and mental retardation limited to females (EFMR). CONCLUSION: To our best knowledge, this is the first time to report Chinese patients diagnosed as Mabry syndrome. For the PCDH19 mutation in our patient carrying PIGV mutations, due to lacking characteristics of EFMR and the ambiguity results in pathogenicity analysis, we were not sure how much pathogenic role PCDH19 mutation shared with PIGV mutations in this disease. The novel mutations of PIGV and PIGO, and novel clinical manifestations reported here might expand the genotype and phenotype spectrum of Mabry syndrome.
Authors: Thi Tuyet Mai Nguyen; Yoshiko Murakami; Kristen M Wigby; Nissan V Baratang; Justine Rousseau; Anik St-Denis; Jill A Rosenfeld; Stephanie C Laniewski; Julie Jones; Alejandro D Iglesias; Marilyn C Jones; Diane Masser-Frye; Angela E Scheuerle; Denise L Perry; Ryan J Taft; Françoise Le Deist; Miles Thompson; Taroh Kinoshita; Philippe M Campeau Journal: Am J Hum Genet Date: 2018-09-27 Impact factor: 11.025
Authors: Alexej Knaus; Jean Tori Pantel; Manuela Pendziwiat; Nurulhuda Hajjir; Max Zhao; Tzung-Chien Hsieh; Max Schubach; Yaron Gurovich; Nicole Fleischer; Marten Jäger; Sebastian Köhler; Hiltrud Muhle; Christian Korff; Rikke S Møller; Allan Bayat; Patrick Calvas; Nicolas Chassaing; Hannah Warren; Steven Skinner; Raymond Louie; Christina Evers; Marc Bohn; Hans-Jürgen Christen; Myrthe van den Born; Ewa Obersztyn; Agnieszka Charzewska; Milda Endziniene; Fanny Kortüm; Natasha Brown; Peter N Robinson; Helenius J Schelhaas; Yvonne Weber; Ingo Helbig; Stefan Mundlos; Denise Horn; Peter M Krawitz Journal: Genome Med Date: 2018-01-09 Impact factor: 11.117