LETTER TO JMG

Hypogonadotropic hypogonadism and cleft lip and palate caused by a balanced translocation producing haploinsufficiency for FGFR1

HG Kim¹, S R Herrick², E Lemyre³, S Kishikawa¹, J A Salisz⁴, S Seminara⁵, M E MacDonald¹, G A P Bruns⁶, C C Morton⁷, B J Quade², J F Gusella¹

¹ Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital/Department of Genetics, Harvard Medical School, Boston, Massachusetts, USA
² Department of Pathology, Brigham and Women’s Hospital/Harvard Medical School
³ Medical Genetics Service, Hôpital Ste Justine, University of Montreal, Montreal, Canada
⁴ West Shore Urology, Mercy Drive, Muskegon, Michigan, USA
⁵ Reproductive Endocrine Unit, Massachusetts General Hospital
⁶ Genetics Division, Children’s Hospital/Department of Pediatrics, Harvard Medical School
⁷ Departments of Obstetrics, Gynecology and Reproductive Biology and Pathology, Brigham and Women’s Hospital/Harvard Medical School

Correspondence to:
Correspondence to:
Dr James F Gusella
Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital/Department of Genetics, Harvard Medical School, CNY149-6214, 13th Street, Boston, Massachusetts 02129, USA; gusella@helix.mgh.harvard.edu

Abbreviations: FGF, fibroblast growth factor; FISH, fluorescent in situ hybridisation; KS, Kallmann’s syndrome; SSCP, single strand conformation polymorphism; UCSC, University of California Santa Cruz

Keywords: balanced translocation; FGFR1; TENS1; Kallmann’s syndrome; hypogonadotropic hypogonadism

The first 150 words of the full text of this article appear below.

We have established the Developmental Genome Anatomy Project (DGAP; //dgap.harvard.edu) to take advantage of the unique opportunity to locate genes of developmental importance provided by apparently balanced chromosomal rearrangements associated with phenotypic abnormalities. By positional cloning at or near the breakpoints, we aim to identify the crucial disease genes whose functions have been disrupted by rearrangement.¹ Kallmann’s syndrome (KS) is a developmental disorder characterised by anosmia resulting from agenesis of the olfactory lobes and hypogonadism secondary to deficiency of hypothalamic gonadotropin releasing hormone (GnRH). Its prevalence has been estimated at 1/10 000 in males and 1/50 000 in females. In a minority of cases there are inactivating mutations of KAL1, an X linked gene encoding a putative adhesion molecule thought to mediate embryonic neuronal migration.^2,3 Constitutional autosomal chromosome translocations associated with KS have been reported, but the disrupted genes have not been identified.^4–6

We have studied a white male subject . . . [Full text of this article]

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