MCPH1 deletion in a newborn with severe microcephaly and premature chromosome condensation.
A newborn with severe microcephaly and a history of parental consanguinity was referred for cytogenetic analysis and subsequently for genetic evaluation. While a 46,XY karyotype was eventually obtained, premature chromosome condensation was observed. A head MRI confirmed primary microcephaly. This combination of features focused clinical interest on the MCPH1 gene and directed genetic testing by sequence analysis and duplication/deletion studies disclosed a homozygous deletion of exons 1-11 of the MCPH1 gene. This case illustrates a strength of standard cytogenetic evaluation in directing molecular testing to a single target gene in this disorder, allowing much more rapid diagnosis at a substantial cost savings for this family.
Department of Pathology and Laboratory Medicine, Nationwide Children's Hospital, Columbus, OH, USA.
Ruthann B
RB
Pfau
Devon Lamb
DL
Thrush
Elizabeth
E
Hamelberg
Dennis
D
Bartholomew
Shaun
S
Botes
Matthew
M
Pastore
Christopher
C
Tan
Daniela
D
del Gaudio
Julie M
JM
Gastier-Foster
Caroline
C
Astbury
D018797:Cell Cycle Proteins; D002877:Chromosomes, Human / Q000235:genetics; D003241:Consanguinity; D003598:Cytoskeletal Proteins; D005091:Exons; D017353:Gene Deletion; D006720:Homozygote; D006801:Humans; D007231:Infant, Newborn; D059785:Karyotype; D008297:Male; D019767:Maxillofacial Abnormalities / Q000175:diagnosis / Q000235:genetics; D008831:Microcephaly / Q000175:diagnosis / Q000235:genetics*; D009419:Nerve Tissue Proteins / Q000235:genetics*; D013577:Syndrome
D018797:Cell Cycle Proteins; D003598:Cytoskeletal Proteins; C460645:MCPH1 protein, human; D009419:Nerve Tissue Proteins
Array-based comparative genomic hybridization; Cell cycle proteins; Consanguinity; Cytogenetic analysis; Genes; Human; MCPH1 protein; Microcephaly; Premature chromosome condensation syndrome; Primary autosomal recessive 1; Recessive