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Identify Waardenburg Syndrome type II Loci in Man

Waardenburg syndrome is one of the most common autosomal dominant syndromes responsible for about 3% of congenital hearing loss. Waardenburg syndrome is characterized by sensorineural deafness and pigmentary abnormalities of the iris, hair, and skin. Waardenburg syndrome is a highly penetrant autosomal dominant disorder that is characterized as a neurocristopathy. The pathophysiology may be a defect in neural crest cells development, differentiation, and/or migration resulting in pleiotropic effects including pigment abnormalities, sensorineural deafness, spina bifida, and Hirschsprung's disease. Several different types of Waardenburg syndrome exist, each with different associations. Hearing loss is the significant feature in Waardenburg syndrome type I and II occurring in 20% and up to 75%, respectively. Several genes have been identified for the different types of Waardenburg syndrome. The Center for Human Genetics at BUSM previously and independently discovered the Waardenburg syndrome type I PAX3 gene. While the majority of individuals with Waardenburg syndrome type II have hearing loss, the genetic etiology is still unknown for the majority of families. Approximately 10-20% of Waardenburg syndrome type II families have mutations in the MITF gene. Hence, the genetic etiology for the vast majority of Waardenburg syndrome type II patients remains unknown. Genome-wide screening to identify genes causing Waardenburg syndrome type II is being conducted within the rubric of a career development award (K23).

Early Hearing Detection and Integration

In a Center for Disease Control sponsored national program, we are one of the selected sites conducting molecular analyses in children with hearing loss. Our analyses are currently focused on the Connexin-26 gene and several mitochondrial gene mutations. The results are being correlated with the thorough audiological assessment conducted on these individuals

publications

Wang Z, Milunsky JM, Yamin M, Maher T, Oates R, Milunsky, A. Analysis of 100 cystic fibrosis gene mutations in 92 patients with congenital bilateral absence of the vas deferens by Mass Spectrometry. Human Reproduction (In Press).

Milunsky JM, Maher, TA, Metzenberg, AB. Molecular, Biochemical, and Phenotypic Analysis of a Hemizygous Male With Non-mosaic X-Linked Dominant Conradi-Hunermann-Happle Syndrome (CDPX2). Am J Med Genet (In Press).

Brown DJ, Kim TB, Petty EM, Downs CA, Martin DM, Strouse PJ, Moroi SE, Milunsky JM, Lesperance MM. Autosomal dominant stapes ankylosis, broad thumbs, hyperopia and skeletal anomalies caused by heterozygous nonsense and frameshift mutations in the noggin gene (NOG). Am J Hum Genet (In Press).

Lebo RV, Maher T, Farrer L, Fenerci EY, Milunsky JM. Highly Polymorphic Short Tandem Repeat Analyses Clarify Complex Molecular Test Results. Diag Mol Path 10(3):179-189; 2001.

McCallum TJ, Milunsky JM, Munarriz R, Carson R, Sadeghi-Nejad H, Oates RD. Unilateral Renal Agenesis (URA) associated with congenital bilateral absence of the vas deferens (CBAVD): Phenotypic findings and genetic considerations in a large cohort of affected men. Human Reproduction 16(2): 282-288; 2001.

Hecht JT, Blanton SH, Broussard S, Scott A, Hall CR, Milunsky JM. Evidence for Locus Heterogeneity in the Camurati-Engelmann (DPDI) Syndrome. Clin Genet 59: 198-200; 2001.

Milunsky JM, Maher TA, Michels VV, Milunsky A. Novel Mutations and the emergence of a common mutation in the SDHD gene causing Familial Paraganglioma. Am J Med Genet 100: 311-314; 2001.

Lebo RV, Ikuta T, Milunsky JM, Milunsky A. Rett Syndrome from quintuple and triple deletions within the MECP2 deletion hotspot region. Clin Genet 59:406-417; 2001.

Milunsky JM, Lebo RV, Ikuta T, Maher TA, Haverty CE, Milunsky A.‹‹Mutation Analysis in Rett Syndrome. Genetic Testing 5(4):321-325;2001.

Wyandt HE, Lebo RV, Fenerci EY, Sadhu DN, Milunsky JM. Tandem duplication/deletion in a maternal supernumerary derivative 9 chromosome resulting in 9p trisomy and partial 9q tetrasomy. Am J Med Genet 93:305-312; 2000.

Vaughn SP, Broussard S, Hall CR, Scott A, Blanton SH, Milunsky JM, Hecht JT. Confirmation of the mapping of the Camurati-Engelmann locus to 19q13.2 and refinement to a 3.2 cM region. Genomics 66(1):119-121; 2000.

McCallum TJ, Milunsky JM, Cunningham DL, Harris DH, Maher TA, Oates RD. Fertility in the Male with Cystic Fibrosis: An Update on Current Surgical Practices and Outcomes. Chest 118: 1059-1062; 2000.

Milunsky JM, Maher TA, Yosunkaya E, Vohr BR. Connexin-26 Gene Analysis in Hearing Impaired Newborns. Genetic Testing 4(4): 345-349; 2000.