Genetics

Question 1

MCC for dwarfism? deficiency in ?

Answer 1

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

Question 2

ADPKD
(automsomal dominant polycystic kidney disease)
ad也可以记忆为adult(原名为adult polycystic kidney disease)

Answer 2

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）

Question 3

familial adenomatous polyposis (FAP)

Answer 3

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

Question 4

familial hypercholesterolemia (hyperlipidemia type IIA) FH

Answer 4

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.

Question 5

hereditary spherocyosis: 遗传特征？gene?

Answer 5

AD; Spheroid RBCs: spectrin or ankyrin defect; hemolytic anemia;
Increased MCHC

Treatment: splenectomy

Question 6

Mafan’s (or Marian’s syn) 遗传特征？gene?

Answer 6

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

Question 7

Huntington’s: 遗传特征？gene?

Answer 7

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

Question 8

Multiple endocrine neoplasias (MEN)

Answer 8

AD; 分MEN1, MEN2A, 2B (2A and 2B: ret gene), family history, endocrine glands affected include pancreas, PT, thyroid, pituitary, adrenal medulla

Question 9

diseases with chr #

Answer 9

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)

Question 10

NF1 (neurofibromatosis type 1; von Recklinghausen’s disease) 神经纤维瘤

Answer 10

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

Question 11

NF2: which chr?

Answer 11

neurofibromatosis type 2 (神经纤维瘤 2型）
AD, gene on chr 22 (= type 2)
bilateral acoustic schwannomas, juvenile cataracts

Question 12

Tuberous sclerosis (TSC, C= complex) 结节性硬化:

遗传特征？gene?

Answer 12

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

Question 13

von Hippel-Lindau disease (VHL): chr?

Answer 13

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

Question 14

AR list

Answer 14

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

Question 15

CF (cystic fibrosis):

Answer 15

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

Question 16

XR list:

Be Wise, Fool’s GOLD Heeds Silly HOpe

Answer 16

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

Question 17

Duchenne’s

Answer 17

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

Question 18

Trinucleotide repeat expansion diseases:

Try (= trinucleotide) HUNTING for MY FRIED EGGS (=X)
X-Girlfriend’s FA Helped Ace My Test.

Answer 18

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

Question 19

Patau’s syn

Answer 19

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

Question 20

Cri-du-chat syn

Answer 20

microdeletion of chr 5p (45, XX or XY-, 5p-)

microcephaly, retardation, high-pitched crying, epicanthal folds, cardiac abnormalities (VSD)

Question 21

Robertonian translocation

Answer 21

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

Question 22

Angelman syn / Prader-Willi Syn (PWS)

the genetic deficit is termed as ??

Answer 22

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

Question 23

Dx: infant has flaccid lower extremities, absent ankle reflexes bilaterally; XR: poorly developed lumber spine and sacrum

associated with ?? in mother

Answer 23

Dx: caudal regression sym

associated with uncontrolled DM in mother

Question 24

Dx: lactic acidosis + ragged (凹凸不平的) red skeletal muscle fibers histologically + neuromuscular lesions

variability in clinical presentation is explained by ?

Answer 24

Dx: mitochondrial encephalomyopathy

variability in clinical presentation is explained by: “heteroplasmy” (异质性）

Question 25

Fragile X syn: what gene mutation - its function? on which chr? Cx? why named so?

Answer 25

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”

Question 26

Dx: myoclonic epilepsy + proximal muscle weakness + muscle biopsy specimen shows fiber with a blotchy red apperance

Answer 26

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

Question 27

adjustment disorder诊断要点？

Answer 27

1. identifiable psychosocial stressors
2. emotional sym causing impairment
3. < 6 m (if chronic stressor, > 6 m)

Question 28

AFP ↑ 见于？

AFP ↓ 见于？

Answer 28

AFP ↑ 见于：omphalocele 脐突出, abdominal wall defects, multiple gestation, neural tube defects (spina bifida, anencephaly),

AFP ↓ 见于: Down syn