New cases and refinement of the critical region in the 1q41q42 microdeletion syndrome.
Microdeletions of 1q41q42 have recently been classified as a syndrome. Features include significant developmental delay and characteristic dysmorphic features as well as cleft palate, clubfeet, seizures, and short stature in some individuals, with a clinical diagnosis of Fryns syndrome in two individuals with congenital diaphragmatic hernia at the severe end of the spectrum. The gene DISP1, which is involved in sonic hedgehog signaling, has been proposed as a candidate for the midline defects in this syndrome. We undertook a genotype-phenotype analysis of seven previously unreported individuals with deletions of 1q41q42 that range from 777 kb to 6.87 Mb. Three of the individuals in our cohort do not display the major features of the syndrome and have more proximal deletions that only overlap with the previously described 1q41q42 smallest region of overlap (SRO) at DISP1. One individual with several features of the syndrome has a more distal deletion that excludes DISP1. The three remaining individuals have larger deletions that include the entire SRO and demonstrate features of the microdeletion syndrome. Confounding genotype-phenotype correlations, one of the small deletions involving DISP1 was inherited from a phenotypically normal parent. DISP1 haploinsufficiency may not be solely responsible for the major features of 1q41q42 microdeletion syndrome, and other genes in the SRO likely play a role in the phenotype. Additionally, some features present in a minority of individuals, such as Pelger-Huët anomaly, may be attributed to deletions of genes outside of the SRO.
Signature Genomic Laboratories, 2820 N. Astor St., Spokane, WA 99207, USA.
Jill A
JA
Rosenfeld
Yves
Y
Lacassie
Dima
D
El-Khechen
Luis F
LF
Escobar
James
J
Reggin
Carolyn
C
Heuer
Emily
E
Chen
Lauren S
LS
Jenkins
A Thomas
AT
Collins
Samuel
S
Zinner
Melanie
M
Babcock
Bernice
B
Morrow
Roger A
RA
Schultz
Beth S
BS
Torchia
Blake C
BC
Ballif
Karen D
KD
Tsuchiya
Lisa G
LG
Shaffer
D000015:Abnormalities, Multiple / Q000235:genetics* / Q000473:pathology; D002648:Child; D002675:Child, Preschool; D002872:Chromosome Deletion; D025063:Chromosome Disorders / Q000235:genetics* / Q000473:pathology; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics*; D015331:Cohort Studies; D055028:Comparative Genomic Hybridization; D019066:Facies; D005260:Female; D056726:Genetic Association Studies; D057895:Haploinsufficiency; D006548:Hernia, Diaphragmatic / Q000235:genetics / Q000473:pathology; D065630:Hernias, Diaphragmatic, Congenital; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D007223:Infant; D017880:Limb Deformities, Congenital / Q000235:genetics / Q000473:pathology; D008297:Male; D013577:Syndrome