syndromes and molecular Flashcards
May-Hegglin anomaly
The gene affected in the May-Hegglin anomaly is MYH-9 on chromosome 22q12-13; defects in this gene are responsible for other closely related large-platelet disorders such as Fechtner, Sebastian, and Epstein syndromes
*The May-Hegglin anomaly is characterized clinically by macrothrombocytopenia and varying degrees of sensorineural hearing loss, cataracts, nephritis, and polymorphonuclear Döhle-like bodies
The May-Hegglin anomaly is characterized clinically by…
The May-Hegglin anomaly is characterized clinically by macrothrombocytopenia and varying degrees of sensorineural hearing loss, cataracts, nephritis, and polymorphonuclear Döhle-like bodies
MYH9 gene on chromosome 22…
*The May-Hegglin anomaly
MYH9 gene on chromosome 22, which encodes the non–muscle heavy chain myosin IIa protein and demonstrates an autosomal dominant pattern of inheritance.
Döhle-like inclusions in neutrophils…
*The May-Hegglin anomaly
Döhle-like inclusions in neutrophils are made of non−muscle myosin heavy chain IIa protein and are devoid of organelles. They differ from bona fide Döhle bodies in that they are characteristically found throughout the cytoplasm of the cell, and they are resistant to treatment with ribonuclease (Döhle bodies are composed of rough endoplasmic reticulum, therefore, having high RNA content).
Chédiak-Higashi syndrome…
Chédiak-Higashi syndrome is a defect in microtubule polymerization (the LYST gene). Clinical features are anemia and neutropenia, recurrent infection (defect in phagocytosis), platelet dysfunction (first-wave aggregation only), oculocutaneous albinism, and neurologic defects. Large granules ranging in color from gray to red can be found in granulocytes, lymphocytes, and monocytes because of defective lysosomes.
(the LYST gene)
Chédiak-Higashi syndrome is a defect in microtubule polymerization (the LYST gene). Clinical features are anemia and neutropenia, recurrent infection (defect in phagocytosis), platelet dysfunction (first-wave aggregation only), oculocutaneous albinism, and neurologic defects. Large granules ranging in color from gray to red can be found in granulocytes, lymphocytes, and monocytes because of defective lysosomes.
predominant inheritance pattern of primary immunodeficiency disorders
More are X-linked resulting in disproportionate number of affected male patients; 70% of primary immunodeficiency disorders occur in male patients
What clinical parameters will be given you to make you think primary immunodeficiency?
Eight or more ear infections in 1 year
Two or more sinus infections in 1 year
Oral antibiotics produce little improvement
Two or more episodes of pneumonia in 1 year
Failure to thrive
Recurring deep skin or organ abscesses
Oral or cutaneus candidiasis after 1 year
One or more episodes of meningitis, osteomyelitis, cellulitis, sepsis
History of autoimmune disease, lymphadenopathy, splenomegaly
Family history of immunodeficiency
The Chédiak-Higashi anomaly…
The Chédiak-Higashi anomaly is characterized by a defect in microtubule polymerization. The morphologic features are markedly enlarged granules found in neutrophils, eosinophils, and lymphoid cells.
What are aCGH or CMA in cytogenetics/molecular?
*Array comparative genomic hybridization (aCGH) or chromosomal microarray analysis (CMA)
**aCGH or CMA is a method used to detect the differences in copy number or dosage of a particular DNA segment between two different DNA samples: the patient sample and the reference DNA sample. This is a rapidly emerging technique in clinical cytogenetics.
Cat-eye syndrome…
Cat-eye syndrome is usually associated with an SMC (supernumerary marker chromosome) derived from chromosome 22. —> (+ mar)
*The SMC is often dicentric and bisatellited and represents an inversion duplication of the genomic material from the proximal short arm to the proximal long arm of chromosome 22.
*There is great variability in the clinical features, especially the congenital malformations.
*The principal clinical features include coloboma of the iris, anal atresia with fistula, downslanting palpebral fissures, preauricular tags &/or pits, and the frequent occurrence of heart and renal malformations.
*Mental development may be near-normal or normal, with as many as 47% of cases falling within the normal range (IQ > 85).
The clinically distinct Prader-Willi and Angelman syndromes involve…
The clinically distinct Prader-Willi and Angelman syndromes involve the same locus on 15q11-13; a deletion of this locus on the paternal chromosome causes Prader-Willi syndrome and on the maternal chromosome causes Angelman syndrome
*paternal absent —> prader
