Verónica Fabiola Morán-Barroso

Velocardiofacial syndrome in Mexican patients: Unusually high prevalence of congenital heart disease

INTRODUCTION Velocardiofacial syndrome (VCFS) is the most common microdeletion syndrome with an incidence of 1:4000 live births. Its phenotype is highly variable with facial, velopharyngeal, cardiac, endocrine, immunologic and psychiatric abnormalities. It is caused by a microdeletion in chromosome 22q11.2. OBJECTIVES We present 7 years of experience evaluating patients with VCFS regarding their main clinical characteristics. MATERIAL AND METHODS The patients included were multidisciplinary evaluated and had a positive FISH analysis for del22q11.2. RESULTS A total of 62 patients were assessed, a 34 female/28 male ratio was observed with ages ranging from 9 days to 16 years, all but one patient had typical facial features. A diagnosis of congenital heart disease was established in 97% of the patients; other clinical characteristics were identified with different percentages such as cleft palate, and hypocalcaemia. Three cases had a familial presentation. DISCUSSION While the clinical findings of this study were in general terms in keeping with the literature, it is interesting the unexpectedly high percentage of congenital heart disease identified in Mexican children with VCFS that also was the main cause for clinical referral.

Polymorphism analysis and new JAG1 gene mutations of Alagille syndrome in Mexican population

Alagille syndrome is a multisystem disorder with an autosomic dominant pattern of inheritance that affects the liver, heart, eyes, kidneys, skeletal system and presents characteristic facial features. Mutations of the JAG1 gene have been identified in 20–89% of the patients with Alagille syndrome, this gene encodes for a ligand that activates the Notch signaling pathway. In the present study we analyzed 9 Mexican patients with Alagille syndrome who presented the clinical criteria for the classical presentation of the disease. By using the denaturing high performance liquid chromatography mutation analysis we were able to identify different mutations in 7 of the patients (77.77%), importantly, we found 5 novel mutations in JAG1 gene. The allelic frequency distribution of 13 polymorphisms in Mexican population is also reported. The overall results demonstrated an expanding mutational spectrum of JAG1 gene in the Mexican population.

Nance–Horan syndrome in females due to a balanced X;1 translocation that disrupts the NHS gene: Familial case report and review of the literature

ABSTRACT The Nance–Horan syndrome is an X-linked disorder characterized by congenital cataract, facial features, microcornea, microphthalmia, and dental anomalies; most of the cases are due to NHS gene mutations on Xp22.13. Heterozygous carrier females generally present less severe features, and up to 30% of the affected males have intellectual disability. We describe two patients, mother and daughter, manifesting Nance–Horan syndrome. The cytogenetic and molecular analyses demonstrated a 46,X,t(X;1)(p22.13;q22) karyotype in each of them. No copy-number genomic imbalances were detected by high-density microarray analysis. The mother had a preferential inactivation of the normal X chromosome; expression analysis did not detect any mRNA isoform of NHS. This is the first report of Nance–Horan syndrome due to a skewed X chromosome inactivation resulting from a balanced translocation t(X;1) that disrupts the NHS gene expression, with important implications for clinical presentation and genetic counseling.

A Novel c.91dupG JAG1 Gene Mutation Is Associated with Early Onset and Severe Alagille Syndrome

Alagille syndrome (MIM 118450) is an autosomal dominant disorder characterized by paucity of intrahepatic bile ducts, chronic cholestasis, pulmonary stenosis, butterfly-like vertebrae, posterior embryotoxon, and dysmorphic facial features. Most cases are caused by JAG1 gene mutations. We report the case of a 2-year-old Mexican mestizo patient with Alagille syndrome, having exhibited jaundice and cholestatic syndrome as of three weeks of age. Sequencing analysis of the JAG1 gene revealed the novel heterozygous mutation c.91dupG that originates a truncated protein and therefore a possibly diminished activation of the Notch signaling pathway. The latter may explain the severe phenotype of the patient. Since the mutation was not identified in the parents, it was considered a de novo event, highlighting the importance of molecular diagnosis and genetic counseling. In conclusion, this report widens the spectrum of JAG1 gene mutations associated with Alagille syndrome.

Mutational spectrum of EDA and EDAR genes in a cohort of Mexican mestizo patients with hypohidrotic ectodermal dysplasia

Hypohidrotic ectodermal dysplasia (HED) has a prevalence of 1:5,000-10,000 newborns and it is characterized by hypotrichosis and abnormalities in teeth and sweat glands.1 Most patients have an X-linked (XLHED) pattern of inheritance due to mutations in EDA which encodes for ectodysplasin. In addition, three HED-associated autosomal genes are known: EDAR which encodes for an ectodysplasin receptor; EDARADD corresponding to a cytoplasmic adaptor molecule and WNT10A which encodes for a signaling molecule of the WNT/β-catenin pathway.1-4 This article is protected by copyright. All rights reserved

Craniosynostosis, delayed closure of the fontanelle, anal, genitourinary, and skin abnormalities (CDAGS syndrome): first report in a Mexican patient and review of the literature

Craniosynostosis and clavicular hypoplasia, delayed closure of the fontanelle, cranial defects, anal and genitourinary abnormalities, and skin (CDAGS), is an infrequent autosomal recessive entity with only 10 cases reported; no associated gene has been identified so far.

Caudal duplication with multicystic dysplastic kidney: a case report.

Departments of Genetics, Urology, Hospital Infantil de México Federico Gómez, Mexico City and Department of Genetics, Hospital Materno Perinatal ‘Mónica Pretelini Saenz’, ISEM, Toluca, Mexico Correspondence to Verónica F. Morán-Barroso, PhD, Department of Genetics, Hospital Infantil de México Federico Gómez, Calle Dr. Márquez 162, Col. Doctores, Del. Cuauhtémoc, C.P. 06720, Distrito Federal, México Tel: + 52 55 52 28 99 17 x2037; fax: + 52 55 57610270; e-mails: vfmoran@himfg.edu.mx and verammx@yahoo.com.mx

Perfil clínico de una cohorte de pacientes con síndrome de Silver-Russell atendidos en el Hospital Infantil de México Federico Gómez de 1998 a 2012

BACKGROUND Patients with Silver-Russell syndrome suffer from severe intrauterine and postnatal growth retardation, relative macrocephaly and body asymmetry, among other characteristics. It is caused by several genetic and epigenetic mechanisms in 11p15.5 in 40% of the cases and maternal uniparental disomy of chromosome 7 in 10%. METHODS Twenty patients with a diagnosis of Silver-Russell syndrome who were seen at the HIMFG from 1998 to 2012, were evaluated according to international clinical criteria confirming the diagnosis in nine of the subjects. RESULTS All patients showed intrauterine and postnatal growth retardation and short stature, both considered as major criteria of Silver-Russell syndrome. Relative macrocephaly was present in 78% of the patients and asymmetry in 33%. Other characteristics such as renal tubular acidosis were present > 50% of the cases. CONCLUSIONS The clinical diagnosis of Silver-Russell syndrome is complex. Short stature is the main reason for seeking medical attention and is helpful in the identification of a differential diagnosis. This situation underlines the importance of growth and development evaluation of all patients and particularly in those with short stature to identify those cases that may require molecular studies, with implications in management, prognosis and genetic counseling.