Genetics Flashcards
MCC for dwarfism? deficiency in ?
Achondroplasia (软骨发育不全）
85% sporadic, if inherited: AD
FGFR3 defects - dwarfism - short limbs, large head, normal trunk size
endochondral osssification deficient vs. membranous ossification is not affected
Normal life span and fertility
associated with advanced parental age
ADPKD
(automsomal dominant polycystic kidney disease)
ad也可以记忆为adult(原名为adult polycystic kidney disease)
AD, (注意：infantile form: AR)
85% due to mutated PDK1 gene (locate on chromosome 16: 16 letters in polycystic kidney)
bilateral enlargement of kidneys, multiple large cysts, flank pain (侧翼痛），hematuria, hypertension, progessive renal failure
associated with polycystic liver, berry aneurysms, mitral valve prolapse (脱垂）
familial adenomatous polyposis (FAP)
AD, APC gene mutation in chr # 5 (5 letters in polyp) 家族性腺瘤性息肉病
colon covered by polyp after puberty, progress to colon cancer unless colon is resected
familial hypercholesterolemia (hyperlipidemia type IIA) FH
AD； defect or absent LDLR
因为是常显，杂合子血液LDL就高达300mg/dL, 纯合子（少见）可高到700 mg/dL； 杂合子发生率1：500 ！！！； normal VLDL and TG
severe atherosclerosis early in life, can have MI before 20; 特征性tendom xanthomas (Achilles tendon)临床特点是高胆固醇血症、特征性黄色瘤、早发心血管疾病和阳性家族史。FH是儿童期最常见的遗传性高脂血症，也是脂质代谢疾病中最严重的一种，可导致各种危及生命的心血管疾病并发症出现，是冠脉疾病的一种重要危险因素。
病例：A 22-year-old woman with a family history of hypercholesterolemia had had a soft-tissue swelling on the back of her left ankle for several years. Examination revealed a fusiform swelling of the Achilles’ tendon.
hereditary spherocyosis: 遗传特征？gene?
AD; Spheroid RBCs: spectrin or ankyrin defect; hemolytic anemia;
Increased MCHC
Treatment: splenectomy
Mafan’s (or Marian’s syn) 遗传特征？gene?
AD; fibrillin-1 gene mutation
connect tissue disorder；tall with long extremities, pectus excavatum, hypermobile joints, tapering fingers and toes; cystic medial necrosis of aorta, floppy mitral valve; subluxation of lenses
Huntington’s: 遗传特征？gene?
AD; Chr#4(Hunting 4 food). Hungtinin
trinucleotide repeat: (CAG)n codon for glutamine
Genetic anticipation 发病越来越早和严重
Depression, progressive dementia, choreiform movements, caudate atrophy, decreased level of GABA and ACh
Multiple endocrine neoplasias (MEN)
AD; 分MEN1, MEN2A, 2B (2A and 2B: ret gene), family history, endocrine glands affected include pancreas, PT, thyroid, pituitary, adrenal medulla
diseases with chr #
Chr 3p: von Hippel-Lindau (3 words)
Chr4: Huntington’s
Chr 5: APC (familial adenomatous polyposis) (5 letters for “polyp”
Chr 5p (microdeletion): Cri-du-chat syn
Chr 7: CF (CFTR gebe)
chr 16: ADPKD（16 letters in “polycystic kidney”)
chr 17: NF type 1 (neurofibromatosis 神经纤维瘤， von Recklinghausen’s disease) 17 letters in “von Recklinghausen”
chr 22: NF type 2 （type 2 = 22)
NF1 (neurofibromatosis type 1; von Recklinghausen’s disease) 神经纤维瘤
AD；one of the most common single-gene disorders affecting neurologic function in humans
mutated gene: neurofibromin on chr #17 long arm, control RAS pathway
特征性皮肤上的cafe-au-lait spots(flat pigmented lesion), 特征性Lisch nodules (pigmented iris hamartomas，错构瘤，不影响视力，但是对诊断NF1非常有用，95%患儿有 )
neural tumors, skeletal disorder (scoliosis脊柱侧凸）， optic pathway glioma
NF2: which chr?
neurofibromatosis type 2 (神经纤维瘤 2型）
AD, gene on chr 22 (= type 2)
bilateral acoustic schwannomas, juvenile cataracts
Tuberous sclerosis (TSC, C= complex) 结节性硬化:
遗传特征？gene?
AD, multi system
主要临床表现：面部皮脂腺瘤、癫痫发作及智能减退为主要特征
facial lesions (adenoma sebaceum), seizures, retardation; hypopigmented “ash leaf spots” on skin
imcomplete penetrance, variable presentation
von Hippel-Lindau disease (VHL): chr?
VHL抑癌基因突变：chr 3P
constitutive expression of HIF and activation of angiogenic growth factors (e.g.., Epo, VEGF)
血管母细胞瘤累及小脑、脊髓、肾脏以及视网膜。其若干病变包括肾脏血管瘤、肾细胞癌以及嗜铬细胞瘤等
AR list
A: albinism, ARPKD (infatile PKD, 和ARPKD区别）
2个贫血：sickle cell anemia, thalassemias
C: cystic fibrosis
糖和脂代谢的病：
G: glycogen storage diseases
M: mucopolysaccharidoese (except Hunter’s)
S: sphingolipidoeses (except Fabry’s - XR)
H: hemochromatosis (血色素沉着病）
P: PKU
CF (cystic fibrosis):
AR; most common fatal genetic disorders in White people
CFTR gene on chr# 7, deletion of Phe 508; CL- folding issue, degraded instead of reaching cell membrane
CFTR (CL- channel) secretes CL- in lungs and GI, absorb CL- from sweat
thick mucus to plug lungs, pancreas, liver
signs: recurrent pulmonary infections (Pseudomonas and S. aureus), pancreatic insufficiency (malabsorption and steatorrhea); fat-soluble V deficiencies (KEAD); fail to thrive in infancy
诊断：increase of CL- in sweat
治疗： N-acetylcysteine to cleave disulfide bonds within mucous glycoproteins - loose the mucus
XR list:
Be Wise, Fool’s GOLD Heeds Silly HOpe
B: Brutons' agammaglobulinemia W: Wiskott-Aldrich sym 维阿二联症 F: Fabry's disease G: G6PD deficiency O: ocular albinism L: Lesch-Nyhan syn D: Duchenne's / Becker's H,S: Hunter's syn H: hemophilia A and B O: OTC
Duchenne’s
XR, frameshift mutation - deletion of dystrophin gene - muscle breakdown
DMD (dysthrophin gene): longest human gene: increase rate of mutation
weakness begins in pelvic gridle muscles, progress superiorly, peudohypertrophy of calf muscle, cardiac myopathy, Gower’s maneuver
与Becker’s 区别：onset before 5
Becker’s: less severe, onset in adolescence or early adulthood
Trinucleotide repeat expansion diseases:
Try (= trinucleotide) HUNTING for MY FRIED EGGS (=X)
X-Girlfriend’s FA Helped Ace My Test.
Hungtingtons’: AD, (CAG)n - Helped Ace
Myotonic dystrophy: (CTG)n -(My Test)
Friedreich’s ataxia (FA): (GAA)n -(FA)
Fragile X syn: (CGG)n - X-Girlgfriend
genetic anticipation
Patau’s syn
Trisomy 13 (puberty = 13)
P= cleft liP/Palate, holoProsencephaly (前脑无裂畸形）， Polydactyly (多指畸形）
severe retardation, rocket-bottom feet, microphthalmia(小眼）, microcephyla, congenital heart disease
孕检: decreasee b-hCG and PAPP-A, increase nuchal translucency
Cri-du-chat syn
microdeletion of chr 5p (45, XX or XY-, 5p-)
microcephaly, retardation, high-pitched crying, epicanthal folds, cardiac abnormalities (VSD)
Robertonian translocation
long arms of 2 acrocentric chromosomes fuse at the centrameres and the 2 short arms are lost
affect chr 13 (Patau), 14, 15, 21 (Downs) and 22
note: 14 and 21 translcoation cause Downs
Angelman syn / Prader-Willi Syn (PWS)
the genetic deficit is termed as ??
sister syn, classical examples of imprinting, affect chromosome #15: microdeletion
Angelman: maternal copy is imprinted (methylated for silencing) in that region
PWS: loss or inactivated Pws gene (or the region) in the paternal cur
the genetic deficit is termed as “uniparental disomy” 单亲二体型 - both members of a given pair of nuclear chromosomes are from the same parent
Dx: infant has flaccid lower extremities, absent ankle reflexes bilaterally; XR: poorly developed lumber spine and sacrum
associated with ?? in mother
Dx: caudal regression sym
associated with uncontrolled DM in mother
Dx: lactic acidosis + ragged (凹凸不平的) red skeletal muscle fibers histologically + neuromuscular lesions
variability in clinical presentation is explained by ?
Dx: mitochondrial encephalomyopathy
variability in clinical presentation is explained by: “heteroplasmy” (异质性）
Fragile X syn: what gene mutation - its function? on which chr? Cx? why named so?
FMR1 (fragile X mental retardation 1) gene on X chr - required in neural development； CGG repeats > 200
Cx: mental retardation, facial dysmorphism, macroorchidism (巨大睾丸）
named: when lymphocytes cultured in folate- and thymidine-depleted media: X-chr appears contricted and thin “fragile”
Dx: myoclonic epilepsy + proximal muscle weakness + muscle biopsy specimen shows fiber with a blotchy red apperance
MERRF (myoclonic epilepsy with ragged red fibers) - MC mt disease
-the “Coma guy’s son” case in House: present as a male, start seizure after light, muscle weakness + intermitent blindness, with a family history
adjustment disorder诊断要点？
- identifiable psychosocial stressors
- emotional sym causing impairment
- < 6 m (if chronic stressor, > 6 m)
AFP ↑ 见于？
AFP ↓ 见于？
AFP ↑ 见于：omphalocele 脐突出, abdominal wall defects, multiple gestation, neural tube defects (spina bifida, anencephaly),
AFP ↓ 见于: Down syn
