Genetics Flashcards
What Gene is mutated in Marfan syndrome
FBN1
What is the inheritance pattern of Klinefelter syndrome
47 XXY
What are common symptoms in adolescence for Klinefelter syndrome
Long legs Gynecomastia Small testes Learning disabilities Psychosocial abnormality
What is the inheritance pattern of Marfan syndrome
Autosomal dominant
What are the syndromes of short stature?
GH deficiency Laron dwarfism noonan turner prader willi angelman
which short stature syndromes are chromosomal
turner
prader willi
angelman
What stays normal with GH deficiency?
intelligence
What does Laron effect?
growth hormone receptor
What are the genetics of Laron?
autosomal recessive
How do you treat GH deficiency?
With GH
How do you test for GH deficiency?
IGF1
What is the release pattern of GH?
pulsatile
Does laron Syndrome respond to GH or IGF1?
IGF1
not GH as there are still no receptors
What gene does dwarfism effect?
FGFR3
What is the genetic pattern of dwarfism?
autosomal dominant
What pathway does FGFR3 work through?
MAP kinase pathway
What is the gene effected by Noonan?
RAS through MAP kinase pathway and increased protein tyrosine phosphatase activity
What is the genetic pattern of Noonan?
autosomal dominant
What are characteristic features of noonan?
neck skin webbing, inverted triangle shaped face, widely spaced nipples, wide forehead, curly/wooly hair, small stature
Is there a specific mutation associated with noonan?
PTPN11
what gene is affected by turner?
SHOX
What does turner syndrome look like on kareotype?
Single X chromosome
What does klinefelter look like on kareotype?
XXY
Which parent has the aneuploidy for turners?
nondisjunction in the father
What two syndromes look similar characteristically?
Turner and Noonan
What chromosome is affected with prader willi?
Chromosome 15, maternal
What are the characteristics of prader willi?
extreme obesity, short stature, intellectual disability, hyperphagia, hypogonadism
What chromosome is affected with angelman?
paternal chromosome 15
Deletion of prader willi syndrome region from paternal chromosome causes?
prader willi syndrome
Deletion of prader willi syndrome region from maternal chromosome causes?
Angelman
what is the most common cause of prader Willi?
deletion of region
What are tall stature syndromes?
GH excess
Sotos
Marfan
Kleinfelter
Characteristics of Kleinfelter syndrome?
tall stature w/ long arms sterile gynocomastia, small testes, androgen deficient learning disability metabolic syndrome
What gene is affected by Kleinfelter?
SHOX
What gene is affected with sotos?
NSD1
What are the genetics of Sotos?
AD haploinsufficiency
what are the genetics of GH excess?
autosomal dominant
How does MEN1 present endocrinely?
pituitary adenoma
parathyroid hyperplasia
pancreatic tumors
How does MEN 2 present endocrinely?
parathyroid hyperplasia
medullary thyroid carcinoma
pheochromocytoma
what gene is affected in MEN 1?
MEN1- loss of function
what is the protein affected with MEN1?
menin (tumor suppressor)
What is the genetic inheritance pattern of MEN1?
autosomal dominant
What gene is affected in MEN2?
RET; gain of function
what is the protein affected in MEN2?
RET; protooncogene
what is the genetic inheritance of MEN2?
autosomal dominant
What is the clinical presentation of MEN2?
high blood calcitonin
What is the clinical presentation of MEN1?
hypercalcemia, hypercaliuria, kidney stones, low bone mass, dehydration, constipation, CVD
What is the difference between MEN2A vs MEN2B mutation?
2A mutation at cysteine rich region and needs to be dimerized
2B mutation at tyrosine kinase, receptor is turned on, does not need dimerization (worst)
What makes FMTC different from other MEN2 mutations?
tumors are only in thyroid gland
What age do you get a total thyroidectomy for MEN2A? MEN2b?
2A- before 5 yo
2B- before 1 yo
How are the HLA genes inherited?
As a haplotype
What HLA types decrease risk of T1DM? Increase?
DR2 & DR5
DR3 & DR4
What is the main no HLA gene associated with TIDM
IDDM2 chromosome 11
Class I- low insulin gene expression increases risk of diabetes
Class III- high insulin gene expression decreased risk of diabetes
What is PPAR gamma? And what is it associated with
Transcription factor
Associated with TIIDM
What variant of PPARG is protective against TIIDM
Pro12Ala
Keeps it more active
What are the functions of PPARG
Insulin sensitization Glucose lowering Triglyceride lowering Anti atherosclerotic Antihypertensive
What is Kir6.2? And what is it associated with
Potassium channel that is needed for insulin release; inc ATP closes k channels leading to insulin release
Regulated by G proteins
Associated with DM type 2
What happens to Kir6.2 in type 2 DM
The k pore doesn’t close so the membrane doesn’t depolarize and so insulin won’t be released
What mutation of Kir6.2 increases type 2 DM risk?
Glu23Lys
What is the most common genetic cause of MODY
MODY3 HNF1alpha Typically activated by insulin AD Mutations cause defective dimerization Defective nuclear translocation Low to no Dna binding
Dx criteria for MODY
Age of onset for at least one family member under 25
Correction of fasting hyperglycemia for at least 2 yrs without insulin
Non ketotic
