DFNB40, a recessive form of sensorineural hearing loss, maps to chromosome 22q11.21-12.1.

We report on a novel localization for a recessive form of deafness (DFNB), by linkage analysis in an Iranian consanguineous family. Affected individuals suffer from prelingual profound sensorineural hearing loss. Genome-wide analysis led to the characterization of a new locus, DFNB40, which maps to an approximately 9 Mb interval between markers D22S427 and D22S1144 at chromosome 22q11.

Loss-of-function mutations in FGFR1 cause autosomal dominant Kallmann syndrome.

We took advantage of overlapping interstitial deletions at chromosome 8p11-p12 in two individuals with contiguous gene syndromes and defined an interval of roughly 540 kb associated with a dominant form of Kallmann syndrome, KAL2. We establish here that loss-of-function mutations in FGFR1 underlie KAL2 whereas a gain-of-function mutation in FGFR1 has been shown to cause a form of craniosynostosis. Moreover, we suggest that the KAL1 gene product, the extracellular matrix protein anosmin-1, is involved in FGF signaling and propose that the gender difference in anosmin-1 dosage (because KAL1 partially escapes X inactivation) explains the higher prevalence of the disease in males.