OBJECTIVE: To explore the clinical characteristics and genetic basis for a child featuring autosomal recessive cutis laxa (ARCL). METHODS: Clinical data of the patient was collected. Trio-whole exome sequencing (trio-WES) was carried out for the proband, his sister and parents. Candidate variant was verified by Sanger sequencing. RESULTS: The 5 years and 2 month old child, was 109.5 cm tall (40% centile) and 14.2 kg in weight (< 3% centile). Physical examination discovered facial dysmorphisms including downslanting palpebral fissure, hypertelorism, broad nasal bridge, prominent forehead, long philtrum, obvious loose and wrinkled of abdominal and groin skin. He also had previous history of cryptorchidism and umbilical hernia. Trio-WES revealed that the child harbored compound heterozygous variants c.1421_1424delAGTC (p.Val476Thrfs*71) and c.2293+1G>A of the ATP6V0A2 gene, both of which were unreported previously. In addition to our patient, 75 cases of ATP6V0A2 gene-related ARCL have so far been diagnosed, with main features including cutis laxa [100% (75/75)], facial dysmorphism [78.7% (59/75)] and delayed closure/large anterior fontanelle [65.3% (49/75)]. Typical facial features have included downslanting palpebral fissures [57.3% (43/75)], broad nasal bridge [40.0% (30/75)] and long face [34.7% (26/75)]. CONCLUSION Patients presenting with generalized skin wrinkling, facial dysmorphism, delayed closure/large anterior fontanelle, mental retardation, global developmental disabilities and seizures should be considered for ATP6V0A2 gene-related ARCL. Exome sequencing may facilitate the identification of genetic etiology, to confirm the diagnosis.
Child ; Cutis Laxa/genetics* ; Humans ; Infant ; Intellectual Disability ; Male ; Proton-Translocating ATPases/genetics* ; Skin ; Exome Sequencing

OBJECTIVE: To carry out genetic diagnosis for a pedigree affected with cutis laxa. METHODS: Genomic DNA was extracted from peripheral blood samples from members of the pedigree and 50 unrelated healthy controls. Potential mutation was screened by next-generation sequencing and verified by Sanger sequencing. RESULTS: A heterozygous c.1985delG mutation was identified in the ELN gene among all patients from this pedigree. The same mutation was not found among unaffected family members and 50 healthy controls. CONCLUSION The genetic etiology for the pedigree has been elucidated, which has enabled genetic counseling and guidance for reproduction.
Cutis Laxa ; genetics ; Elastin ; genetics ; Heterozygote ; High-Throughput Nucleotide Sequencing ; Humans ; Mutation ; Pedigree