Mosaicism Mosaicism Two different genotypes that developed from a - PowerPoint PPT Presentation

Mosaicism

Mosaicism • Two different genotypes that developed from a single fertilized egg • Why? • Event during cell division • Chromosomal mutation during development • Gene mutation during development (somatic) • X-inactivation (females)

Rudolf Happle, M.D. • Well-renowned pediatric dermatologist • Professor in Marburg and Freiburg • Defined several inherited dermatologic conditions • Helped us understand concepts in dermatology

The term mosaicism (somatic segregation) • 1901 Rediscovery of Mendelian inheritance • 1904 Valentin Häcker • Mosaikbastarde: animals showing traits from both of their parents in a mosaic pattern. • 1913 Collins • Variegated pattern in seeds of maize

Jumping Genes • Investigated mosaic patterns in maize • Jumping genes • Epigenetic mosaicism Barbara McClintock

Happle R. Mosaicism in Human Skin

Incontinentia pigmenti The pattern of lesions follows the lines of Blaschko. Also the areas of normal skin alternating with normal skin represent areas of random inactivation of x or X. Widukind Lenz described the alternating lines as an example of X inactivation

Somatic mosaicism • A postzygotic mutation CAN affect gonads, therefore, an individual with type 1 segmental disease may have offsprings with non- segmental involvement! Happle R. Mosaicism in Human Skin

Type 1 segmental involvement • Tuberous sclerosis Trauner MA. J Am Acad Dermatol 2003;49:S164-6

Type 2 segmental involvement Pronounced manifestation in the background of milder diffuse manifestation Heterozygous embryo featuring loss of heterozygosity Ø in the affected area Examples include PTEN hamartoma syndrome

Genomic X-chromosome mosaicism in male patients Incontinentia pigmenti in males • 46,XY males present with incontinentia pigmenti (Bloch-Sulzberger syndrome) because of postzygotic X chromosome NEMO deletions • The other explanation for males affected is 47,XXY karyotype

Patterns of skin involvement • Lines of Blaschko • Checkerboard pattern • Phylloid pattern • Patchy pattern without midline separation • Lateralization pattern • Sash-like pattern

Patterns of skin involvement Happle R. Mosaicism in Human Ski

Epidermal nevus syndromes

Ep Epiderma rmal n nevu vus s s syndrome ome • Sporadic patients • Cutaneous manifestations • Skeletal manifestations • Central nervous system manifestations

Ep Epiderma rmal n nevu vus s s syndrome ome • A syndrome that does not really exist! • Schimmelpenning • Sebaceous gland nevi, CNS anomalies, eye problems • Νevus comedonicus • Cataracts • Pigmented and hairy nevus syndrome • Becker nevus, chest hypoplasia, scoliosis • Proteus syndrome • Hamartomas • CHILD syndrome • Females, congenital hemidysplasia, ichthyosiform erythroderma, limb defects

McCune-Albright syndrome