The Results of CHD7 Analysis in Clinically Well-Characterized Patients with Kallmann Syndrome
JEH Bergman, W de Ronde… - The Journal of …, 2012 - academic.oup.com
JEH Bergman, W de Ronde, MCJ Jongmans, BHR Wolffenbuttel, SLS Drop, A Hermus…
The Journal of Clinical Endocrinology, 2012•academic.oup.comContext: Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in
which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically
heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas
CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the
CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a
minority of KS patients. Objective: We aimed to investigate whether CHD7 mutations can …
which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically
heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas
CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the
CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a
minority of KS patients. Objective: We aimed to investigate whether CHD7 mutations can …
Context
Kallmann syndrome (KS) and CHARGE syndrome are rare heritable disorders in which anosmia and hypogonadotropic hypogonadism co-occur. KS is genetically heterogeneous, and there are at least eight genes involved in its pathogenesis, whereas CHARGE syndrome is caused by autosomal dominant mutations in only one gene, the CHD7 gene. Two independent studies showed that CHD7 mutations can also be found in a minority of KS patients.
Objective
We aimed to investigate whether CHD7 mutations can give rise to isolated KS or whether additional features of CHARGE syndrome always occur.
Design
We performed CHD7 analysis in a cohort of 36 clinically well-characterized Dutch patients with KS but without mutations in KAL1 and with known status for the KS genes with incomplete penetrance, FGFR1, PROK2, PROKR2, and FGF8.
Results
We identified three heterozygous CHD7 mutations. The CHD7-positive patients were carefully reexamined and were all found to have additional features of CHARGE syndrome.
Conclusion
The yield of CHD7 analysis in patients with isolated KS seems very low but increases when additional CHARGE features are present. Therefore, we recommend performing CHD7 analysis in KS patients who have at least two additional CHARGE features or semicircular canal anomalies. Identifying a CHD7 mutation has important clinical implications for the surveillance and genetic counseling of patients.
Oxford University Press