Novel LSS variants in alopecia and intellectual disability syndrome: New case report and clinical spectrum of LSS-related rare disease traits.

TitleNovel LSS variants in alopecia and intellectual disability syndrome: New case report and clinical spectrum of LSS-related rare disease traits.
Publication TypeJournal Article
Year of Publication2023
AuthorsElbendary, HM, Marafi, D, Saad, AK, Elhossini, R, Duan, R, Rafat, K, Jhangiani, SN, Gibbs, RA, Pehlivan, D, Calame, DG, Posey, JE, Lupski, JR, Zaki, MS
JournalClin Genet
Date Published2023 Sep
KeywordsAlopecia, Humans, Intellectual Disability, Male, Mutation, Phenotype, Rare Diseases, Syndrome

Pathogenic biallelic variants in LSS are associated with three Mendelian rare disease traits including congenital cataract type 44, autosomal recessive hypotrichosis type 14, and alopecia-intellectual disability syndrome type 4 (APMR4). We performed trio research exome sequencing on a family with a four-year-old male with global developmental delay, epilepsy and striking alopecia, and identified novel compound heterozygous LSS splice site (c.14+2T>C) and missense (c.1357 G>A; p.V453L) variant alleles. Rare features associated with APMR4 such as cryptorchidism, micropenis, mild cortical brain atrophy and thin corpus callosum were detected. Previously unreported APMR4 findings including cerebellar involvement in the form of unsteady ataxic gait, small vermis with prominent folia, were noted. A review of all reported variants to date in 29 families with LSS-related phenotypes showed an emerging genotype-phenotype correlation. Our report potentially expands LSS-related phenotypic spectrum and highlights the importance of performing brain imaging in LSS-related conditions.

Alternate JournalClin Genet
PubMed ID37157980
Grant ListU01 HG011758 / HG / NHGRI NIH HHS / United States
T32 NS043124 / NS / NINDS NIH HHS / United States
K23 NS125126 / NS / NINDS NIH HHS / United States
K08 HG008986 / HG / NHGRI NIH HHS / United States
T32 AI007526 / AI / NIAID NIH HHS / United States
R35 NS105078 / NS / NINDS NIH HHS / United States
U01 HG011758 / HG / NHGRI NIH HHS / United States
UM1 HG006542 / HG / NHGRI NIH HHS / United States

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