TY - JOUR
T1 - Novel mutations and a severe neurological phenotype in Sjögren-Larsson syndrome patients from Iran
AU - Kariminejad, Ariana
AU - Barzgar, Mohammadreza
AU - Bozorgmehr, Bita
AU - Keshavarz, Elham
AU - Kariminejad, Mohamad Hasan
AU - S'Aulis, Dana
AU - Rizzo, William B.
N1 - Funding Information:
This work was supported in part by the Sjögren-Larsson Syndrome Research Fund ( 01089800 ) at the University of Nebraska Foundation.
Publisher Copyright:
© 2017
PY - 2018/3
Y1 - 2018/3
N2 - Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spasticity and intellectual disability. The disease is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous families. Sequencing of ALDH3A2 identified 4 novel mutations, including a 26-bp deletion (c.25_50del), small in-frame deletion (c.370_372del; p.G124del), a termination (p.Q35Ter) and a missense mutation (p.Lys211Glu). Bacterial expression of the p.Lys211Glu and p.G124del mutations showed little or no detectable enzyme activity. Three of the patients exhibited an unusual neuro-regressive clinical course associated with seizures, which may reflect the presence of unidentified genetic or environmental modifiers in this consanguineous population. This cohort represents the largest group of Iranian patients with molecularly confirmed SLS and expands the mutational and clinical spectrum of this disease.
AB - Sjögren-Larsson syndrome (SLS) is a rare autosomal recessive disorder characterized by ichthyosis, spasticity and intellectual disability. The disease is caused by mutations in the ALDH3A2 gene that encodes fatty aldehyde dehydrogenase. We describe 7 Iranian SLS patients from 5 unrelated consanguineous families. Sequencing of ALDH3A2 identified 4 novel mutations, including a 26-bp deletion (c.25_50del), small in-frame deletion (c.370_372del; p.G124del), a termination (p.Q35Ter) and a missense mutation (p.Lys211Glu). Bacterial expression of the p.Lys211Glu and p.G124del mutations showed little or no detectable enzyme activity. Three of the patients exhibited an unusual neuro-regressive clinical course associated with seizures, which may reflect the presence of unidentified genetic or environmental modifiers in this consanguineous population. This cohort represents the largest group of Iranian patients with molecularly confirmed SLS and expands the mutational and clinical spectrum of this disease.
KW - ALDH3A2
KW - Ichthyosis
KW - Intellectual disability
KW - Spasticity
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U2 - 10.1016/j.ejmg.2017.11.006
DO - 10.1016/j.ejmg.2017.11.006
M3 - Article
C2 - 29183715
AN - SCOPUS:85036514573
SN - 1769-7212
VL - 61
SP - 139
EP - 144
JO - European Journal of Medical Genetics
JF - European Journal of Medical Genetics
IS - 3
ER -