Complex management of a patient with a contiguous Xp11.4 gene deletion involving ornithine transcarbamylase: a role for detailed molecular analysis in complex presentations of classical diseases.
A male infant was diagnosed prenatally with a partial ornithine transcarbamylase (OTC) gene deletion and managed from birth. However, he displayed neurological abnormalities and developed pleural effusions, ascites and anasarca not solely explained by OTC deficiency (OTCD). Further evaluation of the gene locus using exon-specific PCR and high-density SNP array copy number analysis revealed a 3.9-Mb deletion from Xp11.4 to Xp21.1 including five additional gene deletions, three causing the known genetic diseases: Retinitis pigmentosa (RP3), X-linked chronic granulomatous disease (CGD) and McLeod syndrome. The case illustrates (1) the complexities of managing a patient with neonatal onset OTCD, CGD, RP3 and McLeod syndrome, (2) the need for detailed evaluation in seemingly "isolated" gene deletions and (3) the clinical utility of high-density copy number analysis for rapidly characterizing chromosomal lesions.
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Matthew A
MA
Deardorff
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Himabindu
H
Gaddipati
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Paige
P
Kaplan
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Pedro A
PA
Sanchez-Lara
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Neal
N
Sondheimer
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Nancy B
NB
Spinner
Division of Human Genetics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA; Center for Applied Genomics, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Hakon
H
Hakonarson
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Can
C
Ficicioglu
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Jaya
J
Ganesh
Division of Genetics and Metabolism, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
Thomas
T
Markello
Division of Stem Cell Transplantation & Immunology, Children's National Medical Center, Washington, DC, USA.
Brett
B
Loechelt
Division of Genetics and Metabolism, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
Dina J
DJ
Zand
Division of Metabolic Diseases, The Children's Hospital of Philadelphia, Philadelphia, PA, USA.
Marc
M
Yudkoff
Division of Genetics and Metabolism, Children's National Medical Center, 111 Michigan Avenue, NW, Washington, DC 20010, USA.
Uta
U
Lichter-Konecki
D002874:Chromosome Mapping; D041321:Chromosomes, Human, X / Q000235:genetics*; D017809:Fatal Outcome; D017353:Gene Deletion; D040181:Genetic Diseases, X-Linked / Q000235:genetics / Q000378:metabolism; D006105:Granulomatous Disease, Chronic / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007223:Infant; D008297:Male; D009954:Ornithine Carbamoyltransferase / Q000235:genetics / Q000378:metabolism*; D020163:Ornithine Carbamoyltransferase Deficiency Disease / Q000235:genetics* / Q000378:metabolism; D012174:Retinitis Pigmentosa / Q000235:genetics / Q000378:metabolism*
D009954:Ornithine Carbamoyltransferase