Elena Lopez-Rangel

Clinical application of 2.7M Cytogenetics array for CNV detection in subjects with idiopathic autism and/or intellectual disability

Qiao Y, Tyson C, Hrynchak M, Lopez‐Rangel E, Hildebrand J, Martell S, Fawcett C, Kasmara L, Calli K, Harvard C, Liu X, Holden JJA, Lewis SME, Rajcan‐Separovic E. Clinical application of 2.7M Cytogenetics array for CNV detection in subjects with idiopathic autism and/or intellectual disability.

Systemic lupus erythematosus and other autoimmune disorders in children with Noonan syndrome.

Elena Lopez-Rangel, Peter N. Malleson, David S. Lirenman, Benjamin Roa, Joanna Wiszniewska, and M.E. Suzanne Lewis* Department of Medical Genetics, British Columbia’s Children’s and Women’s Health Center, University of British Columbia, British Columbia, Canada Division of Rheumatology, British Columbia’s Children’s and Women’s Hospital, University of British Columbia, British Columbia, Canada Department of Pediatrics, Division of Pediatric Nephrology, British Columbia’s Children’s and Women’s Hospital, University of British Columbia, British Columbia, Canada Department of Molecular and Human Genetics, Baylor DNA Diagnostic Laboratory, Baylor College of Medicine, Houston, Texas Department of Molecular and Human Genetics, Baylor College of Medicine, Houston, Texas Department of Medical Genetics, British Columbia’s Children’s and Women’s Health Center, University of British Columbia, British Columbia, Canada

Genotype-phenotype analysis of 18q12.1-q12.2 copy number variation in autism

Autism Spectrum Disorders (ASD) are complex neurodevelopmental conditions characterized by delays in social interactions and communication as well as displays of restrictive/repetitive interests. DNA copy number variants have been identified as a genomic susceptibility factor in ASDs and imply significant genetic heterogeneity. We report a 7-year-old female with ADOS-G and ADI-R confirmed autistic disorder harbouring a de novo 4 Mb duplication (18q12.1). Our subject displays severely deficient expressive language, stereotypic and repetitive behaviours, mild intellectual disability (ID), focal epilepsy, short stature and absence of significant dysmorphic features. Search of the PubMed literature and DECIPHER database identified 4 additional cases involving 18q12.1 associated with autism and/or ID that overlap our case: one duplication, two deletions and one balanced translocation. Notably, autism and ID are seen with genomic gain or loss at 18q12.1, plus epilepsy and short stature in duplication cases, and hypotonia and tall stature in deletion cases. No consistent dysmorphic features were noted amongst the reviewed cases. We review prospective ASD/ID candidate genes integral to 18q12.1, including those coding for the desmocollin/desmoglein cluster, ring finger proteins 125 and 138, trafficking protein particle complex 8 and dystrobrevin-alpha. The collective clinical and molecular features common to microduplication 18q12.1 suggest that dosage-sensitive, position or contiguous gene effects may be associated in the etiopathogenesis of this autism-ID-epilepsy syndrome.

Overlapping clinical phenotypes : the road to identifying dysmorphology signalling pathways and their associated risks

Germline mutations in HRAS proto‐oncogene cause Costello syndrome
Aoki et al. (2005)
Nature Genetics 37: 1038–1040

NBEA: developmental disease gene with early generalized epilepsy phenotypes

NBEA is a candidate gene for autism, and de novo variants have been reported in neurodevelopmental disease (NDD) cohorts. However, NBEA has not been rigorously evaluated as a disease gene, and associated phenotypes have not been delineated. We identified 24 de novo NBEA variants in patients with NDD, establishing NBEA as an NDD gene. Most patients had epilepsy with onset in the first few years of life, often characterized by generalized seizure types, including myoclonic and atonic seizures. Our data show a broader phenotypic spectrum than previously described, including a myoclonic‐astatic epilepsy–like phenotype in a subset of patients. Ann Neurol 2018;84:796–803

PRENATALLY DETECTED ASYMMETRIC INTRAUTERINE GROWTH RETARDATION AND UMBILICAL CORD RUPTURE DURING DELIVERY IN A CHILD WITH MARSHALL-SMITH SYNDROME.: 303

Marshall-Smith syndrome (MSS) is defined as an “overgrowth” multiple congenital anomalies syndrome that presents with advanced bone age, characteristic craniofacial anomalies, failure to thrive, respiratory difficulties, and global developmental delay. We report an 18-month-old girl who presented prenatally with asymmetric intrauterine growth retardation (IUGR) and polyhydramnios. At birth, she was hypoxic with no respiratory effort due to umbilical cord avulsion during delivery. Birth weight was 2.0 kg (10%), birth length was 45 cm (10%), and OFC was 33.5 cm (60%). She had facial features consistent with Melnick-Needles syndrome; however, filamin A gene mutation testing was negative. A tracheostomy was done at 2 weeks due to severe micrognathia. When seen at 18 months, her weight was 7.43 kg (

The neoplastic risk in children with Noonan syndrome and Costello syndrome

HRAS mutations in Costello syndrome
Estep et al. (2006)
American Journal of Medical Genetics 10‐A: 8–16