A Novel C-Terminal CIB2 (Calcium and Integrin Binding Protein 2) Mutation Associated with Non-Syndromic Hearing Loss in a Hispanic Family.

Hearing loss is a complex disorder caused by both genetic and environmental factors. Previously, mutations in CIB2 have been identified as a common cause of genetic hearing loss in Pakistani and Turkish populations. Here we report a novel (c.

Germline gain-of-function mutations in AFF4 cause a developmental syndrome functionally linking the super elongation complex and cohesin.

Transcriptional elongation is critical for gene expression regulation during embryogenesis. The super elongation complex (SEC) governs this process by mobilizing paused RNA polymerase II (RNAP2). Using exome sequencing, we discovered missense mutations in AFF4, a core component of the SEC, in three unrelated probands with a new syndrome that phenotypically overlaps Cornelia de Lange syndrome (CdLS) that we have named CHOPS syndrome (C for cognitive impairment and coarse facies, H for heart defects, O for obesity, P for pulmonary involvement and S for short stature and skeletal dysplasia).

A de novo 10.79 Mb interstitial deletion at 2q13q14.2 involving PAX8 causing hypothyroidism and mullerian agenesis: a novel case report and literature review.

Reports of interstitial deletions involving proximal long arm of chromosome 2 are limited. Based on early chromosomal analysis studies, the phenotypic consequence of deletions at the ancestral chromosome fusion site at chromosome 2q13q14.1 remains unclear.

Spectrum of elastin sequence variants and cardiovascular phenotypes in 49 patients with Williams-Beuren syndrome.

Haploinsufficiency of the elastin gene (ELN) on 7q11.23 is responsible for supravalvular aortic stenosis (SVAS) and other arteriopathies in patients with Williams-Beuren syndrome (WBS). These defects occur with variable penetrance and expressivity, but the basis of this is unknown.

Severe osteopathia striata with cranial sclerosis in a female case with whole WTX gene deletion.

Osteopathia striata with cranial sclerosis (OSCS) is caused by truncating mutations or deletions in the X linked gene, WTX, and is characterized by sclerotic striations of the metaphyses and diaphyses of long bones, pelvis, and scapula, along with craniofacial hyperostosis. Females typically manifest with craniofacial dysmorphisms including macrocephaly, hypertelorism, depressed nasal bridge, and hypoplastic maxilla, often have cleft palate, and less often extra skeletal anomalies. Here we report on a sporadic female patient with OSCS born at 33 weeks, with coarse facies, an abnormal head shape, cleft palate, pyloric stenosis, a small VSD, and laryngotracheomalacia sufficiently severe to require tracheostomy placement.

17q12 Deletion in a patient with Williams syndrome: Case report and review of the literature.

Williams syndrome (WS) is a complex genomic disorder entailing distinctive facial dysmorphism, cardiovascular abnormalities, intellectual disabilities, unusual behavioral features, and a specific cognitive profile with considerable variability. Additional symptoms include endocrine abnormalities, renal anomalies and connective tissue disorders. We report a monozygotic twin patient with WS who presented with multicystic kidneys in the newborn period, and, in addition to the typical WS deletion at 7q11.

Interstitial duplication of 22q13.2 in a girl with short stature, impaired speech and language, and dysmorphism.

The 22q13.3 deletion syndrome has been widely reported, with a known phenotype including global developmental delay, normal to accelerated growth and a characteristic facial appearance. A duplication syndrome involving this region has also been reported, with a somewhat more variable phenotype including psychomotor retardation, growth restriction, characteristic facial appearance differing from that seen in the deletion syndrome, and multiple malformations.

Dextrocardia, atrial septal defect, severe developmental delay, facial anomalies, and supernumerary ribs in a child with a complex unbalanced 8;22 translocation including partial 8p duplication.

We report on a child with dextrocardia, atrial septal defect (ASD), severe developmental delay, hypotonia, 13 pairs of ribs, left preauricular choristoma, hirsutism, and craniofacial abnormalities. Prenatal cytogenetic evaluation showed karyotype 46,XY,?dup(8p)ish del(8)pter. Postnatal array CGH demonstrated a 6.

Agnathia-otocephaly complex: a case report and examination of the OTX2 and PRRX1 genes.

Agnathia-otocephaly is a rare, often lethal malformation characterized by absence or hypoplasia of the mandible, microstomia, hypoglossia/aglossia, and variable anterior midline fusion of the ears (melotia, synotia). Etiologies have been linked to both genetic and teratogenic factors and to date, a definitive, commonly identifiable cause has not been recognized. Mouse and human genetic studies have implicated OTX2 and PRRX1 as potential candidate genes for agnathia-otocephaly.

A unique presentation of Wiskott-Aldrich syndrome in relation to platelet size.

Wiskott-Aldrich Syndrome (WAS) is a triad of immunodeficiency, eczema, and thrombocytopenia. Despite the heterogeneity of genetic and clinical findings, a correlation with small platelet size is routinely observed. Herein we describe a case with a unique phenotype that links normal mean platelet volume with the classic characteristics of this disease.

Molecular characterization of an interstitial deletion of 1p31.3 in a patient with obesity and psychiatric illness and a review of the literature.

We report on the clinical and array-based characterization of an interstitial 1p31.3 deletion in a 15-year-old male patient with obesity, behavioral problems including multiple psychiatric diagnoses, mild intellectual impairment, facial dysmorphism, and a strong family history of psychiatric illness. The deletion breakpoints were determined by molecular karyotyping, revealing a 3.

Mutational analysis of HOXA2 and SIX2 in a Bronx population with isolated microtia.

Objective: Microtia is a developmental malformation of the external ear with genetic and environmental causes. The prevalence of microtia varies but several studies suggest increased incidence in Hispanic and African American populations. No causal genetic mutations have been identified in these populations.

GJB2 mutation spectrum in 209 hearing impaired individuals of predominantly Caribbean Hispanic and African descent.

Objective: The purpose of the study is to determine whether Caribbean Hispanic and African admixture populations have a paucity of mutations in GJB2, encoding connexin 26.

Methods: We reported the paucity of mutations in GJB2 and deletions in GJB6 in Caribbean Hispanic and African admixture populations in the Bronx, NY, in 2007 [1]. We have now collected 102 additional probands with non-syndromic sensorineural hearing impairment (NSHI), for a total of 209.

Health care supervision for twin pairs.

Twins are at increased risk for congenital anomalies and have particular health care needs, but twin management guidelines do not exist. This review attempts to integrate the latest research findings and evidence-based medicine on twins into basic clinical recommendations for general pediatricians.

Genetic evaluation of American minority pediatric cochlear implant recipients.

Objective: To review the results of genetic evaluation of American minority pediatric cochlear implant recipients over a 5-year period.

Methods: Case series review of pediatric cochlear implant recipients of Caribbean Hispanic and African American admixture descent with severe to profound sensorineural hearing loss at a tertiary care children's hospital.

Results: Out of 28 patients receiving cochlear implants, 14 were of Caribbean Hispanic or African American admixture ancestry.

Mutations in GJB2, GJB6, and mitochondrial DNA are rare in African American and Caribbean Hispanic individuals with hearing impairment.

Autosomal recessive nonsyndromic sensorineural hearing impairment (ARNSHI) comprises 80% of familial hearing loss cases. Approximately half result from mutations in the connexin 26 (Cx26) gene, GJB2, in Caucasian populations. Heterozygous mutations in GJB2 occasionally co-occur with a deletion of part of GJB6 (connexin 30; Cx30).