title: Disruption of DMD and deletion of ACSL4 causing developmental delay, hypotonia, and multiple congenital anomalies.
abstract: We have studied a male patient with significant developmental delay, growth failure, hypotonia, girdle weakness, microcephaly, and multiple congenital anomalies including atrial (ASD) and ventricular (VSD) septal defects. Detailed cytogenetic and molecular analyses revealed three de novo X chromosome aberrations and a karyotype 46,Y,der(X)inv(X) (p11.4q11.2)inv(X)(q11.2q21.32 approximately q22.2)del(X)(q22.3q22.3) was determined. The three X chromosome aberrations in the patient include: a pericentric inversion (inv 1) that disrupted the Duchenne muscular dystrophy (DMD) gene, dystrophin, at Xp11.4; an Xq11.2q21.32 approximately q22.2 paracentric inversion (inv 2) putatively affecting no genes; and an interstitial deletion at Xq22.3 that results in functional nullisomy of several known genes, including a gene previously associated with X-linked nonsyndromic mental retardation, acyl-CoA synthetase long chain family member 4 (ACSL4). These findings suggest that the disruption of DMD and the absence of ACSL4 in the patient are responsible for neuromuscular disease and cognitive impairment.
authors.affiliation: J.C. Self Research Institute of Human Genetics, Greenwood Genetic Center, Greenwood, SC, USA.
authors.forename: S S
authors.initials: SS
authors.lastname: Bhat
authors.forename: K R
authors.initials: KR
authors.lastname: Schmidt
authors.forename: S
authors.initials: S
authors.lastname: Ladd
authors.forename: K C
authors.initials: KC
authors.lastname: Kim
authors.forename: C E
authors.initials: CE
authors.lastname: Schwartz
authors.forename: R J
authors.initials: RJ
authors.lastname: Simensen
authors.forename: B R
authors.initials: BR
authors.lastname: DuPont
authors.forename: R E
authors.initials: RE
authors.lastname: Stevenson
authors.forename: A K
authors.initials: AK
authors.lastname: Srivastava
mesh_terms: D000015:Abnormalities, Multiple / Q000235:genetics*; D001724:Birth Weight; D002648:Child; D002869:Chromosome Aberrations; D041321:Chromosomes, Human, X; D003066:Coenzyme A Ligases / Q000235:genetics*; D002658:Developmental Disabilities / Q000235:genetics*; D016189:Dystrophin / Q000235:genetics*; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008607:Intellectual Disability / Q000235:genetics*; D008297:Male; D009123:Muscle Hypotonia / Q000235:genetics*; D017384:Sequence Deletion; D000098859:Long-Chain-Fatty-Acid-CoA Ligase
chemical_list: C484258:DMD protein, human; D016189:Dystrophin; D003066:Coenzyme A Ligases; D000098859:Long-Chain-Fatty-Acid-CoA Ligase