Variable phenotype in 17q12 microdeletions: clinical and molecular characterization of a new case.
Microdeletions of 17q12 including the hepatocyte nuclear factor 1 beta (HNF1B) gene, as well as point mutations of this gene, are associated with the Renal Cysts and Diabetes syndrome (RCAD, OMIM 137920) and genitourinary alterations. Also, microdeletions encompassing HNF1B were identified as a cause of Mayer-Rokitansky-Küster-Hauser Syndrome (MRKH, OMIM 277000) in females and, recently, were associated with intellectual disability, autistic features, cerebral anomaly and facial dysmorphisms. In this report, we describe a boy with a deletion in 17q12 region detected by SNP array, encompassing the HNF1B gene, that showed dysmorphic features, intellectual disability (ID), serious speech delay and autistic features. In addition, obesity was observed. In order to study the parental origin of the rearrangement, we analyzed selected SNPs in the deleted area in the patient and his parents, showing Mendelian incompatibilities suggesting a de novo deletion on the chromosome of maternal origin. Our case confirms the incomplete penetrance and variable expressivity of this deletion, its complex clinical variability, and strengthens the evidence that ID and stereotyped behaviors may be part of the phenotypic spectrum characterizing the affected patients. Also, it is useful to further delineate the phenotypes associated to the deletion being the first case in which obesity has been documented. We present a genotype-phenotype correlation discussing the possible role of some genes, encompassed by the deletion, in the etiology of the observed phenotypes.
Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy; Department of Biology, University of Bari, Bari, Italy.
Pietro
P
Palumbo
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'ALESSANDRO", Universita' Degli Studi di Palermo, Palermo, Italy.
Vincenzo
V
Antona
Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy.
Orazio
O
Palumbo
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'ALESSANDRO", Universita' Degli Studi di Palermo, Palermo, Italy.
Maria
M
Piccione
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'ALESSANDRO", Universita' Degli Studi di Palermo, Palermo, Italy.
Rosaria
R
Nardello
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'ALESSANDRO", Universita' Degli Studi di Palermo, Palermo, Italy.
Antonina
A
Fontana
Medical Genetics Unit, IRCCS Casa Sollievo della Sofferenza, San Giovanni Rotondo, FG, Italy. Electronic address: m.carella@operapadrepio.it.
Massimo
M
Carella
Dipartimento di Scienze per la Promozione della Salute e Materno Infantile "G. D'ALESSANDRO", Universita' Degli Studi di Palermo, Palermo, Italy.
Giovanni
G
Corsello
D000015:Abnormalities, Multiple / Q000235:genetics; D000103:Acetyl-CoA Carboxylase / Q000235:genetics; D001321:Autistic Disorder / Q000235:genetics; D002648:Child; D002872:Chromosome Deletion; D002886:Chromosomes, Human, Pair 17 / Q000235:genetics*; D005260:Female; D051858:Forkhead Transcription Factors / Q000235:genetics; D057895:Haploinsufficiency / Q000235:genetics; D006239:Haplotypes; D051539:Hepatocyte Nuclear Factor 1-beta / Q000235:genetics; D006801:Humans; D008607:Intellectual Disability / Q000235:genetics; D060850:LIM-Homeodomain Proteins / Q000235:genetics; D007805:Language Development Disorders / Q000235:genetics; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D014157:Transcription Factors / Q000235:genetics
C465448:FOXP2 protein, human; D051858:Forkhead Transcription Factors; C496495:HNF1B protein, human; C085473:LHX1 protein, human; D060850:LIM-Homeodomain Proteins; D014157:Transcription Factors; D051539:Hepatocyte Nuclear Factor 1-beta; D000103:Acetyl-CoA Carboxylase
17q12; HNF1B; Intellectual disability; Renal Cysts and Diabetes syndrome; SNP array