Narrowing critical regions and determining penetrance for selected 18q- phenotypes.
One of our primary goals is to help families who have a child with an 18q deletion anticipate medical issues in order to optimize their child's medical care. To this end we have narrowed the critical regions for four phenotypic features and determined the penetrance for each of those phenotypes when the critical region for that feature is hemizygous. We completed molecular analysis using oligo-array CGH and clinical assessments on 151 individuals with deletions of 18q and made genotype-phenotype correlations defining or narrowing critical regions. These nested regions, all within 18q22.3 to q23, were for kidney malformations, dysmyelination of the brain, growth hormone stimulation response failure, and aural atresia. The region for dysmyelination and growth hormone stimulation response failure were identical and was narrowed to 1.62 Mb, a region containing five known genes. The region for aural atresia was 2.3 Mb and includes an additional three genes. The region for kidney malformations was 3.21 Mb and includes an additional four genes. Penetrance rates were calculated by comparing the number of individuals hemizygous for a critical region with the phenotype to those without the phenotype. The kidney malformations region was 25% penetrant, the dysmyelination region was 100% penetrant, the growth hormone stimulant response failure region was 90% penetrant with variable expressivity, and the aural atresia region was 78% penetrant. Identification of these critical regions suggest possible candidate genes, while penetrance calculations begin to create a predictive phenotypic description based on genotype.
Cody
Jannine D
JD
Department of Pediatrics, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA. cody@uthscsa.edu
Heard
Patricia L
PL
Crandall
Analisa C
AC
Carter
Erika M
EM
Li
John
J
Hardies
L Jean
LJ
Lancaster
Jack
J
Perry
Brian
B
Stratton
Robert F
RF
Sebold
Courtney
C
Schaub
Rebecca L
RL
Soileau
Bridgette
B
Hill
Annice
A
Hasi
Minire
M
Fox
Peter T
PT
Hale
Daniel E
DE
D002869:Chromosome Aberrations; D002874:Chromosome Mapping; D002887:Chromosomes, Human, Pair 18; D004427:Ear Diseases / Q000151:congenital / Q000453:epidemiology / Q000235:genetics; D004432:Ear, Middle / Q000002:abnormalities; D008040:Genetic Linkage; D005838:Genotype; D006130:Growth Disorders / Q000151:congenital / Q000453:epidemiology / Q000235:genetics; D020279:Hereditary Central Nervous System Demyelinating Diseases / Q000453:epidemiology / Q000235:genetics; D006801:Humans; D007668:Kidney / Q000002:abnormalities; D007674:Kidney Diseases / Q000151:congenital / Q000453:epidemiology / Q000235:genetics; D019683:Penetrance; D010641:Phenotype