Classical homocystinu
ria is the most commonly inhe
rited diso
rde
r of sulfu
r metabolism, caused by the genetic alte
rations in human cystathionine beta-synthase (CBS) gene. In this study, we p
resent comp
rehensive clinical findings and the genetic basis of homocystinu
ria in a coho
rt of Tu
rkish patients. Excluding some CBS mutations, detailed genotype-phenotype co
rrelation fo
r diffe
rent CBS mutations has not been established in lite
ratu
re. We aimed to make clinical subg
roups acco
rding to main clinical symptoms and discussed these data togethe
r with mutational analysis
results f
rom ou
r patients. Totally, 16 diffe
rent mutations we
re identified; twelve of which had al
ready been
repo
rted, and fou
r a
re novel (p.N93Y, p.L251P, p.D281V and c.829鈭?A>T). The p
robands we
re classified into th
ree majo
r g
roups acco
rding to the clinical symptoms caused by these mutations. A psychomoto
r delay was the most common diagnostic symptom (n = 12, 46.2% neu
rological p
resentation), followed by th
romboembolic events (n = 6, 23.1% vascula
r p
resentation) and lens ectopia, myopia o
r ma
rfanoid featu
res (n = 5, 19.2% connective tissue p
resentation). Py
ridoxine
responsiveness was 7.7%; howeve
r, with pa
rtial
responsive p
robands, the
ratio was 53.9%.
In addition, five thrombophilic nucleotide changes including MTHFR c.677 C>T and c.1298 A>C, Factor V c.1691 G>A, Factor II c.20210 G>A, and SERPINE1 4G/5G were investigated to assess their contributions to the clinical spectrum. We suggest that the effect of these polymorphisms on clinical phenotype of CBS is not very clear since the distribution of thrombophilic polymorphisms does not differ among specific groups.
This study provides molecular findings of 26 Turkish probands with homocystinuria and discusses the clinical presentations and putative effects of the CBS mutations.