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Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft Lip/Palate.

Xu H, Niu Y, Wang T, Liu S, Xu H, Wang S, Liu J, Ye Z - Biomed Res Int (2015)

Bottom Line: Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP).This mutation was also presented in his healthy father and grandfather.These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China ; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

ABSTRACT
Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP). In order to describe the clinical features, genetic etiology, and treatment outcome of KS males with CLP, we performed genetic screening for 15 known causal IHH genes (KAL1, FGFR1, NELF, FGF8, CHD7, WDR11, SEMA3A, KISS1R, KISS1, PROKR2, PROK2, TAC3, TACR3, GNRH1, and GNRHR) in four KS with CLP patients and six IHH patients without CLP. Two novel heterozygous missense mutations in FGFR1, (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C), were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their healthy parents and 200 normal controls. One novel heterozygous missense mutation in KISS1R, (NM_032551): c.587C>A (p.P196H), was identified in an 18-year-old KS male with cleft lip and dental agenesis who developed sperm after being treated with gonadotropin. This mutation was also presented in his healthy father and grandfather. These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene.

No MeSH data available.


Related in: MedlinePlus

Mutations in three Kallmann syndrome (KS) males with cleft lip/palate. Heterozygous missense mutations in (a) FGFR1, (NM_001174066): c.776G>A (p.G259E) in case 1, (b) KISSR1, (NM_032551): c.587C>A (p.P196H) in case 2, and (c) FGFR1, NM_001174066: c.358C>T (p.R120C) in case 3. For comparison, normal sequences of the corresponding regions are indicated.
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fig2: Mutations in three Kallmann syndrome (KS) males with cleft lip/palate. Heterozygous missense mutations in (a) FGFR1, (NM_001174066): c.776G>A (p.G259E) in case 1, (b) KISSR1, (NM_032551): c.587C>A (p.P196H) in case 2, and (c) FGFR1, NM_001174066: c.358C>T (p.R120C) in case 3. For comparison, normal sequences of the corresponding regions are indicated.

Mentions: We performed Sanger sequencing to rule out false positives and confirmed that 3 of the 21 variants (Table 2) were true mutations. There were no additional mutations in the 456 bp regions of each target gene or in amplicons with less than 50X coverage. In summary, two novel heterozygous missense mutations in FGFR1, (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C) (Figure 2), were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their parents and other heathy family members. One heterozygous missense mutation in KISS1R which was reported previously, (NM_032551): c.587C>A (p.P196H) (Figure 2), was identified in an 18-year-old KS male with cleft lip and dental agenesis. However, it was presented in the healthy father and grandfather of this patient. We did not identify these three mutations in any of the 200 control subjects. Furthermore, we did not identify any mutations in the six IHH/KS patients without CLP.


Novel FGFR1 and KISS1R Mutations in Chinese Kallmann Syndrome Males with Cleft Lip/Palate.

Xu H, Niu Y, Wang T, Liu S, Xu H, Wang S, Liu J, Ye Z - Biomed Res Int (2015)

Mutations in three Kallmann syndrome (KS) males with cleft lip/palate. Heterozygous missense mutations in (a) FGFR1, (NM_001174066): c.776G>A (p.G259E) in case 1, (b) KISSR1, (NM_032551): c.587C>A (p.P196H) in case 2, and (c) FGFR1, NM_001174066: c.358C>T (p.R120C) in case 3. For comparison, normal sequences of the corresponding regions are indicated.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC4496468&req=5

fig2: Mutations in three Kallmann syndrome (KS) males with cleft lip/palate. Heterozygous missense mutations in (a) FGFR1, (NM_001174066): c.776G>A (p.G259E) in case 1, (b) KISSR1, (NM_032551): c.587C>A (p.P196H) in case 2, and (c) FGFR1, NM_001174066: c.358C>T (p.R120C) in case 3. For comparison, normal sequences of the corresponding regions are indicated.
Mentions: We performed Sanger sequencing to rule out false positives and confirmed that 3 of the 21 variants (Table 2) were true mutations. There were no additional mutations in the 456 bp regions of each target gene or in amplicons with less than 50X coverage. In summary, two novel heterozygous missense mutations in FGFR1, (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C) (Figure 2), were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their parents and other heathy family members. One heterozygous missense mutation in KISS1R which was reported previously, (NM_032551): c.587C>A (p.P196H) (Figure 2), was identified in an 18-year-old KS male with cleft lip and dental agenesis. However, it was presented in the healthy father and grandfather of this patient. We did not identify these three mutations in any of the 200 control subjects. Furthermore, we did not identify any mutations in the six IHH/KS patients without CLP.

Bottom Line: Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP).This mutation was also presented in his healthy father and grandfather.These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene.

View Article: PubMed Central - PubMed

Affiliation: Department of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China ; Institute of Urology, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei 430030, China.

ABSTRACT
Kallmann syndrome (KS) is characterized by isolated hypogonadotropic hypogonadism (IHH) with anosmia and is sometimes associated with cleft lip/palate (CLP). In order to describe the clinical features, genetic etiology, and treatment outcome of KS males with CLP, we performed genetic screening for 15 known causal IHH genes (KAL1, FGFR1, NELF, FGF8, CHD7, WDR11, SEMA3A, KISS1R, KISS1, PROKR2, PROK2, TAC3, TACR3, GNRH1, and GNRHR) in four KS with CLP patients and six IHH patients without CLP. Two novel heterozygous missense mutations in FGFR1, (NM_001174066): c.776G>A (p.G259E) and (NM_001174066): c.358C>T (p.R120C), were identified in a 23-year-old KS male with cleft lip and an 18-year-old KS patient with cleft lip and palate, dental agenesis, and high arched palate, respectively. These two mutations were not presented in their healthy parents and 200 normal controls. One novel heterozygous missense mutation in KISS1R, (NM_032551): c.587C>A (p.P196H), was identified in an 18-year-old KS male with cleft lip and dental agenesis who developed sperm after being treated with gonadotropin. This mutation was also presented in his healthy father and grandfather. These results have implications for the diagnosis, genetic counseling, and treatment of KS and CLP males with mutations in FGFR1 gene.

No MeSH data available.


Related in: MedlinePlus