Deletion of and novel missense mutation in POU3F4 in 2 families segregating X-linked nonsyndromic deafness.

Objective: To analyze the physical manifestations and genetic features of 2 families segregating X-linked deafness, which is most commonly reported to be caused by mutations of the POU domain gene POU3F4 at the DFN3 locus.

Design: Computed tomographic study of the temporal bone in probands from each family, followed by mutation screening and deletion mapping of POU3F4 in family members.

Setting: Two midwestern genetics clinics.

Large germline deletions of mitochondrial complex II subunits SDHB and SDHD in hereditary paraganglioma.

More than 30% of adrenal pheochromocytomas are hereditary. These neuroendocrine tumors are major components of three inherited cancer syndromes: multiple endocrine neoplasia type 2, von Hippel-Lindau disease (VHL), and pheochromocytoma/paraganglioma syndrome (PC/PGL). Germline mutations in RET; VHL; and SDHB, SDHC, and SDHD are associated with multiple endocrine neoplasia type 2, VHL, and PC/PGL, respectively.

Temtamy-like syndrome associated with translocation of 2p24 and 9q32.

We describe the phenotype of a 5 year old girl with features resembling Temtamy syndrome, including agenesis of the corpus callosum, ventriculomegaly, frontal bossing, peaked eyebrows, ptosis, malformed and low set ears, a depressed nasal bridge, a long philtrum, and iris and chorioretinal colobomas. Features unique to this child include profound mental retardation, bilateral sensorineural hearing loss, agenesis of the corpus callosum, patent ductus arteriosus, ventricular septal defect, unilateral renal agenesis, neurogenic bladder and hydronephrosis. High resolution chromosome analysis demonstrated a de novo, balanced translocation [46,XX,t(2;9)(p24;q32)]; and her case has some overlapping phenotypic features with cases of monosomy for 2p.

Kousseff syndrome caused by deletion of chromosome 22q11-13.

Kousseff syndrome was originally described by Boris Kousseff in 1984: Pediatrics 74:395-398 in three siblings whose main features were conotruncal heart defects, neural tube defects, and dysmorphic features. The proband is a white male who has spina bifida, shunted hydrocephalus, cleft palate, short stature, cognitive impairment, and the typical craniofacial features of velo-cardio-facial syndrome (VCFS), including low-set and dysplastic ears, broad base of the nose, narrow alae nasi, and retrognathia. The family history is significant for a brother who died at 2 weeks of age with myelomeningocele, hydrocephalus, transposition of the great vessels, and unilateral renal agenesis, and a sister who died at 11 days of age with myelomeningocele, truncus arteriosus, hypocalcemia, and autopsy findings of absent thymus and parathyroid glands, consistent with DiGeorge anomaly.