2 - 18 - GENETICS IN RELATION TO THE SKIN Flashcards
- one parent is affected unless there has been a de novo mutation in a parental gamete
- Males and females are affected in approximately equal numbers
- disorder can be transmitted from generation to generation;
- on average, half the offspring will have the condition
Autosomal dominant
when the phenotype in heterozygous individuals is less than that observed for homozygous subjects
semidominant
For example, ichthyosis vulgaris is a semidominant disorder in which the presence of one or two mutant profilaggrin gene (FLG) alleles can strongly influence the clinical severity of the ichthyosis.
this is the best hallmark of autosomal dominant inheritance which distinguish it from X-linked dominant
male-to-male transmission
both parents are carriers of one normal and one mutated allele for the same gene, and, typically, they are phenotypically unaffected
autosomal recessive
If both of the mutated alleles are transmitted to the offspring, this will give rise to a disorder acquired in which pattern of inheritance?
the risk of which is 25%
Autosomal recessive
If the mutations from both parents are the same, the individual is referred to as a?
homozygote
if different parental mutations within a gene have been inherited, the individual is termed what?
compound heterozygote
if the partner of an individual with an autosomal recessive disorder is also a carrier of the same mutation, albeit clinically unaffected, then there is a 50% chance of the offspring inheriting two mutant alleles and therefore also inheriting the same autosomal recessive disorder. This pattern of inheritance is referred to as?
pseudodominant
difference of XLD to AD
no male-to-male transmission
An affected male transmits the disorder to all his daughters and to none of his sons
both males and females are affected, and the pedigree pattern may resemble that of autosomal dominant inheritance
X-linked dominant
An affected male transmits the disorder to all his daughters and to none of his sons
occur almost exclusively in males, but the gene is transmitted by carrier females, who have the mutated gene only on one X chromosome (heterozygous state).
X-linked recessive conditions
The sons of an affected male will all be normal (because their single X chromosome comes from their clinically unaffected mother)
X-linked recessive conditions
the daughters of an affected male will all be carriers (because all had to have received the single X chromosome from their father that carries the mutant copy of the gene)
X-linked recessive conditions
The number and arrangement of the chromosomes is referred to as?
karyotype
most common numerical abnormality of chromosomes
trisomy
If two chromosomes break, the detached fragments may be exchanged, known as?
If this process involves no loss of DNA, it is referred to as?
reciprocal translocation
balanced translocation
The phenomenon of having mixed mitochondrial DNA species within a cell is known as
heteroplasmy
The presence of a mixed population of cells bearing different genetic or chromosomal characteristics leading to phenotypic diversity is referred to as
mosaicism
Mosaicism for a single gene
somatic mosaicism
indicates a mutational event occurring after fertilization
define the lines of Blaschko
the pattern is attributed to the lines of migration and proliferation of epidermal cells during embryogenesis (ie, the bands of abnormal skin represent clones of cells carrying a mutation in a gene expressed in the skin)
The HLA region is located on the short arm of chromosome 6, at 6p21, referred to as the _____
MHC
Human leukocyte antigen (HLA) molecules are glycoproteins that are expressed on almost all nucleated cells.
Fetal skin biopsies are taken during what trimester?
midtrimester
For disorders such as EB, testing at 16 weeks’ gestation is appropriate. However, for some forms of ichthyosis, the disease-defining structural pathology may not be evident at this time, and fetal skin sampling may need to be deferred until 20 to 22 weeks of development.
Identify the pattern of inheritance
Ichthyosis vulgaris
Autosomal semidominant
Identify the pattern of inheritance
Neurofibromatosis
AD
Identify the pattern of inheritance
Tuberous sclerosis
AD
Identify the pattern of inheritance
Darier disease
AD
Identify the pattern of inheritance
Hailey-Hailey disease
AD
Identify the pattern of inheritance
Lamellar ichthyosis
AR
Identify the pattern of inheritance
Xeroderma pigmentosum
AR
Identify the pattern of inheritance
Junctional epidermolysis bullosa
AR
Identify the pattern of inheritance
Kindler syndrome
AR
Identify the pattern of inheritance
Conradi-Hunermann-Happle syndrome
XLD
Identify the pattern of inheritance
Incontinentia pigmenti
XLD
Identify the pattern of inheritance
Focal dermal hypoplasia
XLD
Identify the pattern of inheritance
X-linked dominant protoporphyria
XLD
Identify the pattern of inheritance
Hypohidrotic ectodermal dysplasia
XLR
Identify the pattern of inheritance
X-linked ichthyosis
XLR
Identify the pattern of inheritance
Wiskott-Aldrich syndrome
XLR
Identify the pattern of inheritance
Fabry disease
XLR
Identify the pattern of inheritance
Menkes syndrome
XLR
Identify the affected gene
Ichthyosis vulgaris
FLG
Identify the affected gene
Neurofibromatosis
NF1
Identify the affected gene
Tuberous sclerosis
TSC1 or TSC2
Identify the affected gene
Darier disease
ATP2A2
Identify the affected gene
Hailey-Hailey disease
ATP2C1
Identify the affected gene
Lamellar ichthyosis
TGM1
Identify the affected gene
Xeroderma pigmentosum
XP-A to XP-G
Identify the affected gene
Junctional epidermolysis bullosa
LAMA3, LAMB3, LAMC2
Identify the affected gene
Kindler syndrome
FERMT1
Identify the affected gene
Conradi-Hunermann-Happle syndrome
EBP
Identify the affected gene
Incontinentia pigmenti
NEMO
Identify the affected gene
Focal dermal hypoplasia
PORCN
Identify the affected gene
X-linked dominant protoporphyria
ALAS2
Identify the affected gene
Hypohidrotic ectodermal dysplasia
EDA, EDA1, HED
Identify the affected gene
X-linked ichthyosis
STS
Identify the affected gene
Wiskott-Aldrich syndrome
WAS
Identify the affected gene
Fabry disease
GLA
Identify the affected gene
Menkes syndrome
MNK
Down syndrome/ Trisomy 21
Edwards Syndrome / Trisomy 18
Patau syndrome / Trisomy 13
Chromosome 4, short arm deletion
Chromosome 5, short arm deletion
Chromosome 18, long arm deletion
Turner syndrome/ 45 XO
Klinefelter syndrome/ 47 XXY
48 XXYY
47 XYY
49 XXXXY
Fragile X syndrome
