ABSTRACT
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.
Subject(s)
Abnormalities, Multiple/genetics , Base Sequence , Chromosomes, Human, Pair 8/chemistry , Homologous Recombination , Limb Deformities, Congenital/genetics , Long Interspersed Nucleotide Elements , Sequence Deletion , Synostosis/genetics , Abnormalities, Multiple/diagnosis , Abnormalities, Multiple/ethnology , Abnormalities, Multiple/pathology , Asian People , Child , DNA Copy Number Variations , Female , Genes, Dominant , High-Throughput Nucleotide Sequencing , Humans , Limb Deformities, Congenital/diagnosis , Limb Deformities, Congenital/ethnology , Limb Deformities, Congenital/pathology , Organic Anion Transporters/deficiency , Organic Anion Transporters/genetics , Sulfotransferases/deficiency , Sulfotransferases/genetics , Synostosis/diagnosis , Synostosis/ethnology , Synostosis/pathologyABSTRACT
We report on seven cases of congenital radio-ulnar synostosis (RUS). Five were found in the same family and two were sporadic. In six the synostosis was bilateral and consistently involved the proximal end of the radius and ulna. In the familial cases the anomaly was inherited as an autosomal dominant trait and was associated with a Dubois sign and relative shortness of metacarpals number 4 and 5 in two patients, and of number 2 in another patient, and of all phalanges of the 5th fingers. These observations suggest involvement of an ulnar developmental field. RUS does not seem to be rare in the Sicilian population.
Subject(s)
Elbow Joint/abnormalities , Synostosis/diagnosis , Synostosis/genetics , Adult , Aged , Elbow Joint/diagnostic imaging , Female , Fingers/abnormalities , Fingers/diagnostic imaging , Humans , Infant , Infant, Newborn , Male , Pedigree , Radiography , Radius/abnormalities , Radius/diagnostic imaging , Sicily/ethnology , Syndrome , Synostosis/ethnology , Ulna/abnormalities , Ulna/diagnostic imaging , Ulna/growth & developmentABSTRACT
Symphalangism was introduced into Hawaii by a Cherokee Indian in the late 1800s. The resultant pedigree, along with two other racially distinct pedigrees, confirms that the condition is an autosomal dominant genetic trait. Associated conditions include carpal and tarsal coalitions, cervical fusions, brachydactylism, symphalangism of the toes, and hearing loss. Surgical intervention in the hands is seldom, if ever, indicated but correction of the associated hearing loss is rewarding.
