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@ARTICLE{Steel:600664,
author = {Steel, Dora Batia Dyne and Danti, Federica Rachele and
Abunada, Mohamed and Kamien, Benjamin and Malhotra, Sony and
Topf, Maya and Kaliakatsos, Marios and Valentine, Jane and
Nemeth, Andrea Hilary and Jayawant, Sandeep and Reid,
Kimberley M. and Mankad, Kshitij and Sudhakar, Sniya and
Ben-Pazi, Hilla and Barwick, Katy and Kurian, Manju A.},
title = {{C}linical {P}henotype in {I}ndividuals {W}ith
{B}irk-{L}andau-{P}erez {S}yndrome {A}ssociated {W}ith
{B}iallelic {SLC}30{A}9 {P}athogenic {V}ariants},
journal = {Neurology},
volume = {100},
number = {21},
issn = {0028-3878},
address = {[Erscheinungsort nicht ermittelbar]},
publisher = {Ovid},
reportid = {PUBDB-2023-08087},
pages = {10},
year = {2023},
abstract = {AbstractBackground and ObjectivesBirk-Landau-Perez syndrome
is a genetic disorder caused by biallelic pathogenic
variants in SLC30A9 presenting with a complex movement
disorder, developmental regression, oculomotor
abnormalities, and renal impairment. It has previously been
reported in 2 families. We describe the clinical phenotype
of 8 further individuals from 4 unrelated families with
SLC30A9-related disease.MethodFollowing detailed clinical
phenotyping, 1 family underwent research whole-genome
sequencing (WGS), 1 research whole-exome sequencing, and 2
diagnostic WGS. Variants of interest were assessed for
pathogenicity using in silico prediction tools, homology
modeling, and, where relevant, sequencing of complementary
DNA (cDNA) for splicing effect.ResultsIn 2 unrelated
families of Pakistani origin (1 consanguineous and 1 not),
the same homozygous missense variant in SLC30A9 (c.1253G>T,
p.Gly418Val) was identified. Family 1 included 2 affected
brothers, and family 2 one affected boy. In family 3, also
consanguineous, there were 4 affected siblings homozygous
for the variant c.1049delCAG, pAla350del. The fourth family
was nonconsanguineous: the 1 affected individual was
compound heterozygous for c.1083dup, p.Val362Cysfs*5, and
c.1413A>G, p.Ser471=. Despite phenotypic variability between
the 4 families, all affected patients manifested with a
progressive hyperkinetic movement disorder, associated with
oculomotor apraxia and ptosis. None had evidence of severe
renal impairment. For the novel missense variant, the
conformation of the loop domain and packing of transmembrane
helices are likely to be disrupted based on structure
modeling. Its presence in 2 unrelated Pakistani families
suggests a possible founder variant. For the synonymous
variant p.Ser471=, an effect on splicing was confirmed
through cDNA analysis.DiscussionPathogenic variants in
SLC30A9 cause a progressive autosomal recessive neurologic
syndrome associated with a complex hyperkinetic movement
disorder. Our report highlights the expanding disease
phenotype, which can present with a wider spectrum of
severity than has previously been recognized.},
cin = {CSSB-LIV/UKE-MT},
ddc = {610},
cid = {$I:(DE-H253)CSSB-LIV_UKE-MT-20220525$},
pnm = {899 - ohne Topic (POF4-899)},
pid = {G:(DE-HGF)POF4-899},
experiment = {EXP:(DE-MLZ)NOSPEC-20140101},
typ = {PUB:(DE-HGF)16},
pubmed = {pmid:37041080},
UT = {WOS:000992164200016},
doi = {10.1212/WNL.0000000000207241},
url = {https://bib-pubdb1.desy.de/record/600664},
}