Novel mutation of IL1RAPL1 gene in a nonspecific X-linked mental retardation (MRX) family

• Published in: American journal of medical genetics. Part A Vol. 146A; no. 24; pp. 3167 - 3172
• Main Authors: Nawara, Magdalena, Klapecki, Jakub, Borg, Katarzyna, Jurek, Marta, Moreno, Sarah, Tryfon, Jolanta, Bal, Jerzy, Chelly, Jamel, Mazurczak, Tadeusz
• Format: Journal Article
• Language: English
• Published: Hoboken Wiley Subscription Services, Inc., A Wiley Company 15.12.2008; Wiley-Liss; Wiley
• Subjects: Adolescent; Adult; Adult and adolescent clinical studies; Biochemistry, Molecular Biology; Biological and medical sciences; Child, Preschool; Chromosomes, Artificial, Bacterial; Chromosomes, Human, X - genetics; Classical genetics, quantitative genetics, hybrids; Clone Cells; Cytogenetic Analysis; deletion; Family; Female; Fundamental and applied biological sciences. Psychology; Genetics; Genetics of eukaryotes. Biological and molecular evolution; Human; Humans; IL1RAPL1; In Situ Hybridization, Fluorescence; Infant; Intellectual deficiency; Interleukin-1 Receptor Accessory Protein - genetics; Life Sciences; linkage analysis; Magnetic Resonance Imaging; Male; Medical genetics; Medical sciences; Mental Retardation, X-Linked - genetics; Middle Aged; Mutation - genetics; Neuropsychological Tests; nonspecific XLMR (MRX); Pedigree; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; X-linked mental retardation (XLMR); Chromosomal aberration; Genetic mapping; Sex linked character; Family study; nonspecific XLMR (MRX); Developmental disorder; Mental retardation; Genetic determinism; Genetic disease; X-linked mental retardation (XLMR); Gene; linkage analysis; Genetic linkage; IL1RAPL1; Intellectual deficiency; Deletion; Family environment; Genetics; X-Chromosome; Mutation; Complex syndrome
• ISSN: 1552-4825; 1552-4833
• DOI: 10.1002/ajmg.a.32613

Mental retardation (MR) affects approximately 2% of the population. About 10% of all MR cases result from defects of X‐linked genes. Mutations in most of more than 20 known genes causing nonspecific form of X‐linked MR (MRX) are very rare and may account for less than 0.5–1% of MR. Linkage studies in extended pedigrees followed by mutational analysis of known MRX genes in the linked interval are often the only way to identify a genetic cause of the disorder. We performed linkage analysis in several MRX families, and in one family with four males with MR we mapped the disease to an interval encompassing Xp21.2–22.11 (with a maximum LOD score of 2.71). Subsequent mutation analysis of genes located in this interval allowed us to identify a partial deletion of the IL1RAPL1 gene. Different nonoverlapping deletions involving IL1RAPL1 have been reported previously, suggesting that this region could be deletion‐prone. In this report, we present the results of the molecular analyses and clinical examinations of four affected family members with the deletion in IL1RAPL1. Our data further confirm the importance and usefulness of linkage studies for gene mapping in MRX families and demonstrate that IL1RAPL1 plays an important role in the etiology of MRX. With the development of new methods (aCGH, MLPA), further rearrangements in this gene (including deletions and duplications) might be discovered in the nearest future. © 2008 Wiley‐Liss, Inc.