Joint effect of the SMN2 and SERF1A genes on childhood-onset types of spinal muscular atrophy in Serbian patients
2015
Аутори:
Brkusanin, MilosKosac, Ana
Jovanović, Vladimir
Pesovic, Jovan
Brajuskovic, Goran
Dimitrijevic, Nikola
Todorovic, Slobodanka
Romac, Stanka
Rasic, Vedrana Milic
Savic-Pavicevic, Dusanka
Тип документа:
Чланак у часопису (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт:
Spinal muscular atrophy (SMA) is caused by functional loss of the
survival of motor neuron 1 (SMN1) gene. Despite genetic homogeneity,
phenotypic variability indicates the involvement of disease modifiers.
SMN1 is located in 5q13.2 segmental duplication, enriched in genes and
prone to unequal rearrangements, which results in copy number
polymorphism (CNP). We examined the influence of CNP of 5q13.2 genes and
their joint effect on childhood-onset SMA phenotype. Multiplex
ligation-dependent probe amplification (MLPA) was used to construct
5q13.2 alleles and assess copy number of the SMN2, small EDRK-rich
factor 1A (SERF1A) and NLR family apoptosis inhibitory protein (NAIP)
genes in 99 Serbian patients with SMN1 homozygous absence (23-type I,
37-type II and 39-mild type III) and 122 patients' parents. Spearman
rank test was performed to test correlation of individual genes and SMA
type. Generalized linear models and backward selection were performed to
obtain a model explaining phenotypic variation with the smallest set of
variables. 5q13.2 alleles most commonly associated with type I harbored
large-scale deletions, while those detected in types II and III
originated from conversion of SMN1 to SMN2. Inverse correlation was
observed between SMN2, SERF1A and NAIP CNP and SMA type (P = 2.2e - 16,
P = 4.264e - 10, P = 2.722e - 8, respectively). The best minimal model
describing phenotypic variability included SMN2 (P<2e -16), SERF1A (P<2e
-16) and their interaction (P=0.02628). SMN2 and SERF1A have a joint
modifying effect on childhood-onset SMA phenotype.
Извор:
Journal of Human Genetics, 2015, 60, 11, 723-728
DOI: 10.1038/jhg.2015.104
ISSN: 1435-232X