First successful application of preimplantation genetic diagnosis and haplotyping for congenital hyperinsulinism.
Congenital hyperinsulinism is the most common cause of persistent hypoglycaemia in infancy. Early surgical intervention is usually required to prevent brain damage. The prevention of the transmission to the offspring is important in families carrying the mutated gene. Preimplantation genetic diagnosis (PGD) is an early genetic testing procedure for couples at risk of transmitting inherited diseases. A 36-year-old Saudi woman married to her first cousin with four affected children was referred for PGD. The hyperinsulinism disease was caused by a novel homozygous mutation in the KCNJ11 gene, an arginine 301 to proline (R301P) substitution.PGD was achieved by whole genome amplification followed by mutation detection combined with short tandem repeat identifier analysis in the first cycle and with haplotyping in the second cycle. The first and second cycles resulted in the births of healthy twin girls and a boy, respectively. As far as is known, this is the first application of PGD to hyperinsulinism. A feasible strategy including whole genome amplification followed by direct mutation detection combined with haplotyping is described.Utilizing haplotyping increases the efficiency of PGD diagnosis as well as confirming the genetic diagnosis. It reveals the parental origin of each inherited chromosome.
Department of Pathology and Laboratory Medicine, King Faisal Specialist Hospital and Research Center, 11211 Riyadh, Saudi Arabia.
Wafa
W
Qubbaj
Abdulrahman
A
Al-Swaid
Saad
S
Al-Hassan
Khalid
K
Awartani
Hesham
H
Deek
Serdar
S
Coskun
D000328:Adult; D020732:Cytogenetic Analysis / Q000379:methods; D004252:DNA Mutational Analysis; D005192:Family Health; D005260:Female; D006239:Haplotypes; D006579:Heterozygote; D006801:Humans; D046768:Nesidioblastosis / Q000151:congenital / Q000175:diagnosis / Q000235:genetics; D020641:Polymorphism, Single Nucleotide; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics; D011247:Pregnancy; D011256:Pregnancy Outcome; D019836:Preimplantation Diagnosis; D020554:Sperm Injections, Intracytoplasmic; D000099161:Kcnj11 Channel
D024661:Potassium Channels, Inwardly Rectifying; D000099161:Kcnj11 Channel