Copy number variations (CNVs) have been well documented to contribute significantly to some genetic disorders; however their frequency is currently not well established in many rare conditions. Here we describe the development, validation and clinical implementation of a custom oligonucleotide-based array CGH platform for the detection of exonic deletions and duplications in 54 genes, primarily implicated in neurodevelopmental disorders, for which our laboratory currently offers clinical sequence analysis.

Autosomal recessive primary microcephaly (MCPH) is characterized by congenital microcephaly and mental retardation (MR) with no other neurological findings.  Mutations in the ASPM gene are the most common etiology of MCPH, causing approximately 40% of cases with a strict diagnosis of MCPH.  Several other genes, including CDK5RAP2, CENPJ, MCPH1, STIL, and CEP152 have been reported to cause MCPH in a small number of families.  These genes are all thought to play a role in cell division.  

We report a unique neurodegenerative disorder characterized by early-onset epilepsy, ataxia, progressive cognitive decline and retinitis pigmentosa (RP) in a highly consanguineous family of Pakistani origin. Affected members are three siblings including a 28-year-old male, 23-year-old female, and 15-year-old male, as well as their 30-year-old female cousin, clearly suggesting an autosomal recessive disorder. All affected individuals experienced a highly similar clinical course characterized by juvenile-onset seizures, retinitis pigmentosa and cognitive decline.

The burgeoning utility of microarray-based comparative genomic hybridization has led to the characterization of a novel 4q21 microdeletion syndrome.  The literature to date reports several major features common to patients with 4q21 microdeletion syndrome including neonatal muscular hypotonia, severe psychomotor retardation, marked progressive growth restriction, absent or severely delayed speech and distinctive facial features.

Human tails are rare congenital anomalies typically noted in otherwise normal infants.  We present a two-day-old male born by vaginal delivery at full term to a 25-year-old G3P2 mother.  Both parents were of non-consanguineous, Hispanic ancestry. There were no known teratogenic exposures during the pregnancy.  Birth weight, length, and head circumference were all within the 50^th to 75^th percentiles.

Medical education has progressively moved towards curricula that feature concept-based courses, decreased lecture time, discipline integration, and increased small-groups with active learning. In response many medical schools have developed integrated courses where medical genetics is integrated with biochemistry, cell biology or both. An additional challenge is to provide clinical relevance to the basic science curriculum. Medical students are also challenged with a transition in learning and problem solving.

Oral-facial-digital syndrome type I (OFDSI) is a multiple anomaly syndrome inherited as an X-linked dominant trait.  OFDS1 is caused by defects in the OFD1 gene, which maps to Xp22.2.  Almost all affected individuals are female, since the condition is almost always prenatally lethal in males.  Common manifestations, as the name of the condition implies, affect the face, mouth, and digits.  Facial manifestations include apparent hypertelorism, underdeveloped alae nasi, and micrognathia.   Oral findings include accessory frenulae (webs in the mouth), abnormal lobation or benign tumor

The University of Chicago provides testing of the ZEB2 gene for Mowat-Wilson syndrome.  MowatWilson.org is an organization established by one family to help others with this diagnosis.  Here is an article by their founders, Dave and Deby Curry, that introduces you to their grandson and their organization:

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