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J Clin Endocrinol Metab. 2014 Oct;99(10):E2138-43. doi: 10.1210/jc.2014-2110. Epub 2014 Jul 31.

The prevalence of CHD7 missense versus truncating mutations is higher in patients with Kallmann syndrome than in typical CHARGE patients.

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  • 1EA7331 Faculté des Sciences Pharmaceutiques (S.M., C.D.), 75006 Paris, France; Laboratoire de Biologie et Génétique Moléculaires (J.S., C.L., C.F., C.D.), Hôpital Cochin, Assistance Publique-Hôpitaux de Paris, 75014 Paris, France; Service de Pédiatrie et de Génétique Médicale (P.P., C.M.), Centre Hospitalier Universitaire Morvan, 29200 Brest, France; Department of Reproduction and Gynecological Endocrinology (S.W.), PL-15-1276 Bialystok, Poland; Service de Génétique (M.G.), Centre Hospitalier Régional Clémenceau, 14033 Caen, France; Service de Génétique Médicale (E.B.), Hôpital Purpan, 31059 Toulouse, France; Service de Pédiatrie (F.K.), Hôpital Bel Air, 57126 Thionville, France; Service d'Edocrinologie (O.V.-M.), Centre Hospitalier, 59322 Valenciennes, France; UF de Génétique Clinique (L.P.), Hôpital Robert Debré, Assistance Publique-Hôpitaux de Paris, 75019 Paris, France; Service de Médecine et d'Endocrinologie (F.A.), Hôpital du Cluzeau, 87042 Limoges, France; Service d'Endocrinologie (S.C.), Hôpital Trousseau, and Service d'Endocrinologie (S.C.-M.), Hôpital St Antoine, Assistance Publique-Hôpitaux de Paris, 75012 Paris, France; Service d'Endocrinologie (P.R.), Centre Hospitalier, 49933 Angers, France; Department of Clinical Genetics (H.H.), University Hospital, DK-1165 Copenhagen, Denmark; Department of Medical Genetics (T.P.), Hospital HF Rikshospital, 0424 Oslo, Norway; Service de Génétique Médicale (D.L.), Hôpital Pellegrin, 33076 Bordeaux, France; Service d'Endocrinologie (P.T.), Groupe Hospitalier Pitié-Salpêtrière, Assistance Publique-Hôpitaux de Paris, 75013 Paris, France; Service d'Endocrinologie (S.H.), Hôpital l'Archet, 06003 Nice, France; Service de Gynécologie Endocrinienne (D.D.), Hôpital Jeanne de Flandre, 59037 Lille, France; Service d'Endocrinologie (J.Y.), Hôpital Bicêtre, Assistance Publique-Hôpitaux de Paris, 94275 Le Kremlin-Bicêtre, France; and Service d'Endocrinologie (M.P.), Hôpital Neurologiqu

Erratum in

  • J Clin Endocrinol Metab. 2015 Jan;100(1):317.



Mutations in CHD7, a gene previously implicated in CHARGE (coloboma, heart defect, choanal atresia, retardation of growth and/or development, genital hypoplasia, ear anomalies) syndrome, have been reported in patients presenting with Kallmann syndrome (KS) or congenital hypogonadotropic hypogonadism (CHH). Most mutations causing CHARGE syndrome result in premature stop codons and occur de novo, but the proportion of truncating vs nontruncating mutations in KS and CHH patients is still unknown.


The objective of the study was to determine the nature, prevalence, mode of transmission, and clinical spectrum of CHD7 mutations in a large series of patients.


We studied 209 KS and 94 CHH patients. These patients had not been diagnosed with CHARGE syndrome according to the current criteria. We searched for mutations in 16 KS and CHH genes including CHD7.


We found presumably pathogenic mutations in CHD7 in 24 KS patients but not in CHH patients. Nontruncating mutations (16 missense and a two-codon duplication) were more prevalent than truncating mutations (three nonsense, three frame shift, and a splice site), which contrasts with patients presenting with typical CHARGE syndrome. Thus, the clinical spectrum associated with CHD7 mutations may be partly explained by genotype/phenotype correlations. Eight patients also had congenital deafness and one had a cleft lip/palate, whereas six had both. For 10 patients, the presence of diverse features of the CHARGE spectrum in at least one relative argues against a de novo appearance of the missense mutation, and this was confirmed by genetic analysis in five families.


Considering the large prevalence and clinical spectrum of CHD7 mutations, it will be particularly relevant to genetic counseling to search for mutations in this gene in KS patients seeking fertility treatment, especially if KS is associated with deafness and cleft lip/palate.

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