A 590 kb deletion caused by non-allelic homologous recombination between two LINE-1 elements in a patient with mesomelia-synostosis syndrome.
Mesomelia-synostoses syndrome (MSS) is a rare, autosomal-dominant, syndromal osteochondrodysplasia characterized by mesomelic limb shortening, acral synostoses, and multiple congenital malformations due to a non-recurrent deletion at 8q13 that always encompasses two coding-genes, SULF1 and SLCO5A1. To date, five unrelated patients have been reported worldwide, and MMS was previously proposed to not be a genomic disorder associated with deletions recurring from non-allelic homologous recombination (NAHR) in at least two analyzed cases. We conducted targeted gene panel sequencing and subsequent array-based copy number analysis in an 11-year-old undiagnosed Japanese female patient with multiple congenital anomalies that included mesomelic limb shortening and detected a novel 590 Kb deletion at 8q13 encompassing the same gene set as reported previously, resulting in the diagnosis of MSS. Breakpoint sequences of the deleted region in our case demonstrated the first LINE-1s (L1s)-mediated unequal NAHR event utilizing two distant L1 elements as homology substrates in this disease, which may represent a novel causative mechanism of the 8q13 deletion, expanding the range of mechanisms involved in the chromosomal rearrangements responsible for MSS.
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Tomohiro
T
Kohmoto
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Takuya
T
Naruto
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Miki
M
Watanabe
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Yuji
Y
Fujita
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Sae
S
Ujiro
Department of Oral and Maxillofacial Surgery, Kobe University Graduate School of Medicine, Kobe, Japan.
Nana
N
Okamoto
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.|The Support Center for Advanced Medical Sciences, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Hideaki
H
Horikawa
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Kiyoshi
K
Masuda
Department of Human Genetics, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.|The Support Center for Advanced Medical Sciences, Graduate School of Biomedical Sciences, Tokushima University, Tokushima, Japan.
Issei
I
Imoto
D000015:Abnormalities, Multiple / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D044466:Asian People; D001483:Base Sequence; D002648:Child; D002898:Chromosomes, Human, Pair 8 / Q000737:chemistry*; D056915:DNA Copy Number Variations; D005260:Female; D005799:Genes, Dominant; D059014:High-Throughput Nucleotide Sequencing; D059765:Homologous Recombination; D006801:Humans; D017880:Limb Deformities, Congenital / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology; D020084:Long Interspersed Nucleotide Elements; D027361:Organic Anion Transporters / Q000172:deficiency / Q000235:genetics; D017384:Sequence Deletion; D015238:Sulfotransferases / Q000172:deficiency / Q000235:genetics; D013580:Synostosis / Q000175:diagnosis / Q000208:ethnology / Q000235:genetics* / Q000473:pathology
D027361:Organic Anion Transporters; C551029:SLCO5A1 protein, human; C470791:SULF1 protein, human; D015238:Sulfotransferases
8q13 deletion; LINE-1; Mesomelia-synostoses syndrome; non-allelic homologous recombination; non-recurrent deletion