Reproductive Pre/Post Natal

Angelman syndrome results from absence of a functional copy of the UBE3A gene inherited from the mother.

The gene responsible in this disorder, blm, was mapped to 15q26.1 and its product was found to encode a RecQ DNA helicase.  It is involved in DNA replication and repair.  Bloom syndrome is an autosomal recessive disorder.  The predominant mutation is referred to as “blmAsh”, a 6-bp deletion and 7-bp insertion at nucleotide position 2281.

Canavan disease is caused by a defective aspa gene.  This gene is located on the p arm of chromosome 17, and is responsible for the production of the enzyme aspartoacylase.  This deficiency leads to the buildup of N-acetylaspartic acid (NAA) in the brain.  The accumulated NAA causes a chemical imbalance resulting in myelin destruction.  Canavan disease is an autosomal recessive disorder.

CF is caused by a mutation in the cystic fibrosis transmembrane conductance regulator (CFTR) gene, found at the q31.2 locus of chromosome 7.  The CFTR gene produces a chloride ion channel important in creating sweat, digestive juices, and the mucus glands of the lungs, liver, pancreas, and intestines.  CF develops when neither allele can produce a functional CFTR protein.  CF is an autosomal recessive disease.

DiGeorge syndrome is caused by a deletion on chromosome 22.  Approximately 90% of patients with DiGeorge syndrome have a deletion at the 22q11.2 region.  A small number of cases of DGS have defects on other chromosomes, notably 10p13. DiGeorge syndrome is inherited in an autosomal dominant manner.

Trisomy 18 or Edwards Syndrome is a genetic disorder caused by the presence of an extra copy of all or part of chromosome 18.  The extra chromosome 18 is retained because of a nondisjunction event during meiosis. The incidence increases as the mother's age increases. The syndrome has a very low rate of survival, resulting from heart abnormalities, kidney malformations, and other internal organ disorders.

Clotting factor II, or prothrombin, located on chromosome 11, is a vitamin K–dependent proenzyme that functions in the blood coagulation cascade.  Factor II deficiency is a rare, inherited or acquired bleeding disorder.  The prothrombin G20210A mutation alters the polyadenylation site of the gene and results in increased mRNA synthesis with a subsequent increase in protein expression.  This mutation results in increased levels of plasma prothrombin and a concurrent increased risk for the development of thrombosis and hypercoagulability which may contribute to infertility.

Fragile X syndrome is the most common inherited form of mental retardation.  It is an X-linked dominant condition that is associated with an expansion of a trinucleotide repeat sequence (CGG)n located on chromosome Xq27.3.  This expansion results in a failure to express the FMR1 gene product, which is required for normal neural development.  In individuals with Fragile X syndrome, the FMR1 allele contains over 200 copies of the (CGG) trinucleotide repeat sequence.  Risk for Fragile X syndrome is determined by the length of the repetitive (CGG) sequence.

Gaucher disease is an autosomal recessive, lysosomal storage disorder, caused by a mutation in the acid β-glucosidase gene, located on chromosome 1q21.  This results in the accumulation of the substrate glucosylceramide and other glycolipids due to a deficiency of beta-glucocerebrosidase.  Gaucher disease is divided into three phenotypic forms.

• Kallmann syndrome is characterized by the association of congenital hypogonadotropic hypogonadism with anosmia (HHA)
• Kallmann syndrome 1 (KS1), caused by mutations in KAL1, is inherited in an X-linked manner
• KS2 (caused by mutations in FGFR1), KS3 (caused by mutations in PROKR2), and KS4 (caused by mutations in PROK2) are inherited in an autosomal dominant manner
• KAL1, FGFR1, PROKR2, and PROK2 are the only genes known to be associated with Kallmann syndrome (KS).  Together, mutations in these genes account for about 20%-25% of KS.

Klinefelter's syndrome, 47,XXY or XXY syndrome is a condition caused by a chromosome aneuploidy. Affected individuals have at least two X chromosomes and at least one Y chromosome. The extra X chromosome is retained because of a nondisjunction event during meiosis (sex cell division).

Maple Syrup Urine Disease (MSUD) is caused by a deficiency of the metabolic enzyme branched-chain α-keto acid dehydrogenase (BCKDH).  This deficiency leads to a buildup of the branched-chain amino acids (leucine, isoleucine, and valine) and their toxic by-products in the blood and urine.  Several forms of the disease include classic severe MSUD, intermediate MSUD, intermittent MSUD, thiamine-responsive MSUD and E3-Deficient MSUD with lactic acidosis.  MSUD is inherited in an  autosomal recessive manner.