American Journal of Medical Genetics 38:608-611 (1991)
Brief Clinical Report Interstitial Deletion of the Long Arm of Chromosome 6 Associated With Absent Pulmonary Valve Hitoshi Horigome, Takako Takano, Takeki Hirano, Takako Kajima, and Shin-ichi Ohtani Department of Pediatrics, Ibaraki Children's Hospital, Mito-shi (H.H., T.H., T.K.), Department of Cardiovascular Surgery, Mito-Saiseikai General Hospital, Mito-Shi (S.-i.O.), Ibaraki-ken, and Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo, (T.T),Japan
We report on a newborn infant with a deletion of 6q and absent pulmonary valve. His chromosome constitution was 46,XY,del (6) (q15q21). To our knowledge this is the first case with such combination.Some of his clinical features were found in common in 2 previous 6q- cases with the same breakpoints. KEY WORDS: chromosome 6q deletion, multiple congenital anomalies, mental retardation INTRODUCTION To date 25 cases of deletion of 6q have been reported. Fourteen cases had interstitial deletion. They include 3 cases with del(6) (q13q15),2 cases with del(6) (q15q21), and 2 cases with del(6) (q16q22).The other 7 cases have variable deleted portions. We have studied an infant with del(6) (q15q21) associated with absent pulmonary valve, a rare congenital heart defect. This is the third case with the same breakpoints. In all 3 cases most of the clinical findings are similar and some of them are different from cases with other deleted portions. CLINICAL REPORT The propositus was the first child of healthy unrelated parents, a 30-year-old father and 28-year-old primigravid mother. The pregnancy was uncomplicated. He was born at 40 weeks of gestation by cesarean section because of fetal distress. BW, BL, and OFC were 2,552 g, 50 cm, and 31 cm, respectively. Apgar score was 2 at 5 minutes, when he was resuscitated. At age 1 day he was transferred to our hospital. On admission respirations were shallow with mildly cyanotic lips. He had brachycephaly, facial flattening, Received for publication January 8,1990; revision received May 22, 1990. DepartAddress reprint requests to Hitoshi Horigome, M.D., ment of Pediatrics, Ibaraki Children's Hospital, Futabadai 3-3-1, Mito-shi, Ibaraki-ken 3 11-41, Japan.
0 1991 Wiley-Liss, Inc.
borderline hypertelorism (a ratio of the distance between the bilateral median epicanthus to that of external was 0.341, apparently low-set and small malformed ears with prominent crura antihelicis and large upper helixes, flat nasal bridge, bulbous nose, micrognathia, and thin vermillion border (Fig. 1). On auscultation of the heart, a to-and-fro murmur was heard. Two-dimensional echocardiogram showed Tetralogy of Fallot with a remnant of pulmonary valve and markedly dilated pulmonary artery. Based on these findings the diagnosis of absent pulmonary valve sequence was made. There was generalized muscle hypotonia with few voluntary movements. Feeding difficulty necessitated gavage feeding right after the birth. No genital anomaly was found except for hyperpigmentation of the scrotum. Bilateral triphalagia of the thumbs was noted without clinodactyly. Chest radiograms showed gradually increasing hyperexpansion of the lungs and he was mechanically ventilated from age 2 months. Then cardiac catheterization, angiographies (Fig. 21, and bronchofiberscopywere performed, showing that the cause of respiratory failure was compression of the bronchus mainly by the dilated right pulmonary artery and right aortic arch. At 3 months, plication and suspension of the right pulmonary artery was performed, resulting in successful weaning from the ventilator. However, on the 40th postsurgical day, respiratory failure recurred. At age 11months he was 72 cm long ( - 1.0 standard deviation: SD), weighed 6.6 kg ( - 3.0 SD), and had an OFC of 41 cm ( - 3.6 SD). Although he started to smile, head control was absent and he was unable to sit up. Computed tomogram of the brain showed only mild cortical atrophy. He was treated with radical operation of the heart. However, he died of low cardiac output on the 5th postsurgical day. Post-mortem examination was not allowed. Dermatoglyphic analysis showed the following: no simian lines, ulnar loops were present on all fingers except for whorl on the 4th fingers, atd angles were 55" (right) and 52" (left),which represented moderately distal axial triradius, and the hallucal patterns were whorl (right), loop distal (left).
6q-
609
Fig. 1. Anterior and oblique view of the patient's face a t age 1 month.
Fig. 2. Antero-posterior view of right ventriculogram. Note extremely dilated right pulmonary artery (RPA).
et al., 19851 (Table I), and 11 cases with presumably terminal deletion. However, we are aware of only 2 reports with the same breakpoints as in our patient. They shared some clinical abnormalities including feeding difficulties, psychomotor retardation, brachycephaly, flat face, hypertelorism, bulbous nose, apparently lowset and malformed ears, "fish-like" mouth, and long philtrum. The patient of Nakagome et al. [19801showed overriding aorta and intermittent episodes of dyspnea, and was suspected of having absent pulmonary valve syndrome. There are 2 other cases showing deletions widely overlapping with our case [Ccite et al., 1981; Schwartz et al., 19841. Their breakpoints were q16 and q22, so that a part of the bands q16 and q21 was deleted in common with our case. Their clinical manifestations also included microcephaly, brachycephaly, prominent fore-
6
CYTOGENETIC STUDIES Cytogenetic analysis was performed on peripheral blood lymphocyte cultures using high-resolution chromosome G-banding. In all 20 cells examined a n interstitial deletion of 6q was seen with breakpoints a t q15 and q21: [46,XY,del (6) (ql5q2l)l (Fig. 3, 850 bands per haploid set [ISCN, 19851).The parents had normal chromosomes. DISCUSSION Some 2 dozen cases with deletion of a portion of 6q have been reported. They include 14 cases with interstitial deletion [Ccite et al., 1981; Glover et al., 1988; Kueppers et al., 1977; Lonardo et al., 1988; Matkins et al., 1987; McNeal et al., 1977; Nakagome et al., 1980; Park et al., 1988; Schwartz et al., 1984; Slater et al., 1988;Turleau e t al., 1988;Yamamoto et al., 1986; Young
p
7
deK6) 6
D:
"I " I
I I
Fig. 3. Chromosome 6 pair of the patient. Arrows indicate breakpoints that showed interstitial deletion of bands q15 and q21. The diagram is of chromosome 6 at 850 bands per haploid set according to ISCN [19851.
610
Horigome et al. TABLE I. Clinical Manifestations of Patients With Interstitial Deletion of 6q* Young Turleau Nakaaome Glover et ;I. et al. et a]. Present et al. 119851 119881 119801 [19881 119901
Slater Lonardo et al. et al. 119881 119881
McNeal et al. 119771
Yamamoto et al. 119861
Deleted segment qllq15 q12q14 F M Sex Term 37 w Gestation 2,800 2,260 Birthweight (g) + Short stature i Microcephaly Prominent forehead Brachycephaly Abnormal face Mongoloid slant Antimongoloid slant Microphthalmia Hypertelorism Hypotelorism + Epicanthic folds + Strabismus Cataract Nasal bridge Bulbous nose Low-set ears Large ears Malformed ears Fish-like mouth Thin vermilion + border Prognathism + Micrognathia + Hieh-arch palate Cleft palate Long philtrum Shallow + Short neck Widely separated nipples VSD Congenital heart disease Small penis + Cryptorchidism Hydronephrosis Cystic kidneys + + Umbilical hernias Large joint stiffness Equinovarus Equinovalgus Scoliosis Clinodactyly (5th finger) + Abnormal palmar creases Feeding difficulties + Delayed devel+ opment Seizures + Hypotonus Hypertonicity Brain atrophy on CT 3m Age described in 9m case report
q13q15 F 37 w 2.600
q13q15 M Term 3.200
+
Macro
-
Scapho Asym
Dolicho
+
+
+ + +
q13q15 q14q16 F F 40 w 2,420 2,800
+
+ -
-
+
q15q21 M 3,000
q15q21 q15q21 q16q22 M M F 37 w 40 w 1,900 2,550 2,450 -
+ +
+
-
+
+
t
Broad
Flat
+
+
Flat t
-
+ + Flat + -
+ +
CBte Schwartz Young Kueppers Park et Matkins et al. et al. a]. et al. et al et al. 119811 119841 rig851 119881 [I9871 rig771
+
+
+ + Flat -
+ + + + -
-
+
-
-
+ -
+
q16q22 M
q21q22 M
q21q27 M
-
+
+ +
+
-
+
-
-
+ + -
+
+ + PDA
PDA
i
+
i
Almond
i
+
-
+ t
+
Flat
+ +
+
+ + +
+
Flat
+ + + + +
+
+
+ +
+
+
+
+
-
Broad
Promi
+
+
+
Promi i
Small
+
t
-
+
i
-I
i
+ + +
q23q24 M Term 2,600
-
-
Short
q22q23 F
Term 2,720
-
+
+
+
+
+ Kyphosis
+
+
-
+
t -
+
+
i
+
+
+
i
-
+ +
+
+
+
+
+
+
-
-
-
+ +
+
-
i
36 m
13 y
32 m
+
-
24 m
33w death
4m
llm death
+ + +
-
+a
t
+a
2y
12y
+ +
+
-
i
+
13y8 m
15m
+
i
+ + 4y3m
2y
*Fifteen cases, including the present case, with interstitial deletion of6q are presented in the order from proximal to distal deletion. macro, macrocephaly; scapho, scaphocephaly; dolicho, dolichocephaly; asym, asymmetrical; promi, prominent; VSD, ventricular septa1 defect; PDA, patent ductus arteriosus. "Initial hypotonia turned hypertonicity later.
head, hypertelorism, bulbous nose, and malformed ears. They differed on the basis of hypertonicity, antimongoloid slant, and highly arched palate. We reviewed 25 cases of deletion of 6q and found that the breakpoints were widely spread all over the arm. The most common breakpoints were q25 (7 cases), q15 (6 cases), q23 (5 cases), q21(4 cases), and q22 (4 cases). In interstitial deletions q15 and q21 were frequently broken. Cases with proximal deletion (cen-ql5) had some clinical features in common. All of them showed umbilical hernia and delayed development. Short stature, mongoloid slant, short neck, epicanthic folds, and abnor-
mal palmar creases were also found in most of them. On the other hand, patients with distal deletions (q21lq22ter) had no features in common except for delayed development (Table I). In spite of some differences of the phenotype in cases with overlapped deleted portions, this paper could contribute to the delineation of the phenotype of 6q - as a clinical entity. The present case had absent pulmonary valve sequence, a unique type of Tetralogy of Fallot. Although it is a well-recognized entity, there have not been any reports of any type of chromosome abnormality associ-
6q-
ated with it. To our knowledge, the present case is the only case with such a combination.
ACKNOWLEDGMENTS The authors are extremely grateful to Dr. Yasuo Nakagome of the National Children’s Medical Research Center in Tokyo. We also thank the staffs in Special Reference Laboratory in Japan for their initial chromosome analysis.
REFERENCES CBte GB, Papadakou-Lagoyanni C, Metaxotou C (1981) : A de nouo interstitial deletion of band q21 on chromosome 6. Ann Genet (Paris) 24:170-171. Glover G, Lopez I, Gabarr6n J, Carmona JA (1988):Partial monosomy 6q (q15q21) by de nouo interstitial deletion. Clin Genet 33:308-310. ISCN (1985): An international system for human cytogenetic nomenclature (1985)-high resolution banding. Cytogenet Cell Genet 35:48-65. Kueppers F, Dewald G, Gordon H, Pineda A (1977): Exclusion of the HLA locus from a large portion of the long arm chromosome 6. Hum Hered 27:242-246. Lonardo F, Colantuoni M, Festa B, Gentile G, Guerritore G, Perone L,
611
Santulli B, Ventruto V (1988): A malformed girl with a de nouo proximal 6q deletion. Ann Genet (Paris) 31:57-59. Matkins SV, Meyer J E , Berry AC (1987):A child with partial monosomy 6q secondary to a maternal direct insertional event. J Med Genet 23:227-229. McNeal RM, Skoglunt RR, Francke U (1977): Congenital anomalies including the VATER association in a patient with a del(6)q deletion. J Pediatr 91:957-960. Nakagome Y, Tanaka T, Hashimoto T, Kuyama M, Maruyama M (1980): Interstitial deletion 6q in a malformed boy. Ann Genet (Paris) 23:49-51. Park JP, Graham JM, Jr, Berg SZ, Wurster-Hill DH (1988):A de novo interstitial deletion of chromosome 6(q22.2q23.1). Clin Genet 33:65-68. Schwartz MF, Kaffe S, Wallace S, Desnick R J (1984):Interstitial deletion of the long arm of chromosome 6[de1(6) (q16q22)J:Case report and review of the literature. Clin Genet 26:574-578. Slater HR, Robb A, Forsyth LA, Hamilton DA, Clark MC, Galloway CAS (1988): Interstitial deletion (6)(qll+ q15) in an infant with congenital abnormalities. J Med Genet 25:210-211. Turleau C, Demay G, Cabanis MO, Lenoir G, de Grouchy J (1988):6ql monosomy: A distinctive syndrome. Clin Genet 34:38-42. Yamamoto Y, Okamoto N, Shiraishi H, Yanagisawa M, Kamoshita S (1986):Deletion of proximal 6q: A clinical report and review of the literature. Am J Med Genet 25467-471. Young RS, Fidone GS, Reider-Garcia PA, Hansen KL, McCombs JL, Moore CM (1985): Deletion of the long arm of chromosome 6 Two new cases and review of the literature. Am J Med Genet 20:21-29.
Brief Clinical Report Interstitial Deletion of the Long Arm of Chromosome 6 Associated With Absent Pulmonary Valve Hitoshi Horigome, Takako Takano, Takeki Hirano, Takako Kajima, and Shin-ichi Ohtani Department of Pediatrics, Ibaraki Children's Hospital, Mito-shi (H.H., T.H., T.K.), Department of Cardiovascular Surgery, Mito-Saiseikai General Hospital, Mito-Shi (S.-i.O.), Ibaraki-ken, and Department of Clinical Genetics, The Tokyo Metropolitan Institute of Medical Science, Honkomagome, Bunkyo-ku, Tokyo, (T.T),Japan
We report on a newborn infant with a deletion of 6q and absent pulmonary valve. His chromosome constitution was 46,XY,del (6) (q15q21). To our knowledge this is the first case with such combination.Some of his clinical features were found in common in 2 previous 6q- cases with the same breakpoints. KEY WORDS: chromosome 6q deletion, multiple congenital anomalies, mental retardation INTRODUCTION To date 25 cases of deletion of 6q have been reported. Fourteen cases had interstitial deletion. They include 3 cases with del(6) (q13q15),2 cases with del(6) (q15q21), and 2 cases with del(6) (q16q22).The other 7 cases have variable deleted portions. We have studied an infant with del(6) (q15q21) associated with absent pulmonary valve, a rare congenital heart defect. This is the third case with the same breakpoints. In all 3 cases most of the clinical findings are similar and some of them are different from cases with other deleted portions. CLINICAL REPORT The propositus was the first child of healthy unrelated parents, a 30-year-old father and 28-year-old primigravid mother. The pregnancy was uncomplicated. He was born at 40 weeks of gestation by cesarean section because of fetal distress. BW, BL, and OFC were 2,552 g, 50 cm, and 31 cm, respectively. Apgar score was 2 at 5 minutes, when he was resuscitated. At age 1 day he was transferred to our hospital. On admission respirations were shallow with mildly cyanotic lips. He had brachycephaly, facial flattening, Received for publication January 8,1990; revision received May 22, 1990. DepartAddress reprint requests to Hitoshi Horigome, M.D., ment of Pediatrics, Ibaraki Children's Hospital, Futabadai 3-3-1, Mito-shi, Ibaraki-ken 3 11-41, Japan.
0 1991 Wiley-Liss, Inc.
borderline hypertelorism (a ratio of the distance between the bilateral median epicanthus to that of external was 0.341, apparently low-set and small malformed ears with prominent crura antihelicis and large upper helixes, flat nasal bridge, bulbous nose, micrognathia, and thin vermillion border (Fig. 1). On auscultation of the heart, a to-and-fro murmur was heard. Two-dimensional echocardiogram showed Tetralogy of Fallot with a remnant of pulmonary valve and markedly dilated pulmonary artery. Based on these findings the diagnosis of absent pulmonary valve sequence was made. There was generalized muscle hypotonia with few voluntary movements. Feeding difficulty necessitated gavage feeding right after the birth. No genital anomaly was found except for hyperpigmentation of the scrotum. Bilateral triphalagia of the thumbs was noted without clinodactyly. Chest radiograms showed gradually increasing hyperexpansion of the lungs and he was mechanically ventilated from age 2 months. Then cardiac catheterization, angiographies (Fig. 21, and bronchofiberscopywere performed, showing that the cause of respiratory failure was compression of the bronchus mainly by the dilated right pulmonary artery and right aortic arch. At 3 months, plication and suspension of the right pulmonary artery was performed, resulting in successful weaning from the ventilator. However, on the 40th postsurgical day, respiratory failure recurred. At age 11months he was 72 cm long ( - 1.0 standard deviation: SD), weighed 6.6 kg ( - 3.0 SD), and had an OFC of 41 cm ( - 3.6 SD). Although he started to smile, head control was absent and he was unable to sit up. Computed tomogram of the brain showed only mild cortical atrophy. He was treated with radical operation of the heart. However, he died of low cardiac output on the 5th postsurgical day. Post-mortem examination was not allowed. Dermatoglyphic analysis showed the following: no simian lines, ulnar loops were present on all fingers except for whorl on the 4th fingers, atd angles were 55" (right) and 52" (left),which represented moderately distal axial triradius, and the hallucal patterns were whorl (right), loop distal (left).
6q-
609
Fig. 1. Anterior and oblique view of the patient's face a t age 1 month.
Fig. 2. Antero-posterior view of right ventriculogram. Note extremely dilated right pulmonary artery (RPA).
et al., 19851 (Table I), and 11 cases with presumably terminal deletion. However, we are aware of only 2 reports with the same breakpoints as in our patient. They shared some clinical abnormalities including feeding difficulties, psychomotor retardation, brachycephaly, flat face, hypertelorism, bulbous nose, apparently lowset and malformed ears, "fish-like" mouth, and long philtrum. The patient of Nakagome et al. [19801showed overriding aorta and intermittent episodes of dyspnea, and was suspected of having absent pulmonary valve syndrome. There are 2 other cases showing deletions widely overlapping with our case [Ccite et al., 1981; Schwartz et al., 19841. Their breakpoints were q16 and q22, so that a part of the bands q16 and q21 was deleted in common with our case. Their clinical manifestations also included microcephaly, brachycephaly, prominent fore-
6
CYTOGENETIC STUDIES Cytogenetic analysis was performed on peripheral blood lymphocyte cultures using high-resolution chromosome G-banding. In all 20 cells examined a n interstitial deletion of 6q was seen with breakpoints a t q15 and q21: [46,XY,del (6) (ql5q2l)l (Fig. 3, 850 bands per haploid set [ISCN, 19851).The parents had normal chromosomes. DISCUSSION Some 2 dozen cases with deletion of a portion of 6q have been reported. They include 14 cases with interstitial deletion [Ccite et al., 1981; Glover et al., 1988; Kueppers et al., 1977; Lonardo et al., 1988; Matkins et al., 1987; McNeal et al., 1977; Nakagome et al., 1980; Park et al., 1988; Schwartz et al., 1984; Slater et al., 1988;Turleau e t al., 1988;Yamamoto et al., 1986; Young
p
7
deK6) 6
D:
"I " I
I I
Fig. 3. Chromosome 6 pair of the patient. Arrows indicate breakpoints that showed interstitial deletion of bands q15 and q21. The diagram is of chromosome 6 at 850 bands per haploid set according to ISCN [19851.
610
Horigome et al. TABLE I. Clinical Manifestations of Patients With Interstitial Deletion of 6q* Young Turleau Nakaaome Glover et ;I. et al. et a]. Present et al. 119851 119881 119801 [19881 119901
Slater Lonardo et al. et al. 119881 119881
McNeal et al. 119771
Yamamoto et al. 119861
Deleted segment qllq15 q12q14 F M Sex Term 37 w Gestation 2,800 2,260 Birthweight (g) + Short stature i Microcephaly Prominent forehead Brachycephaly Abnormal face Mongoloid slant Antimongoloid slant Microphthalmia Hypertelorism Hypotelorism + Epicanthic folds + Strabismus Cataract Nasal bridge Bulbous nose Low-set ears Large ears Malformed ears Fish-like mouth Thin vermilion + border Prognathism + Micrognathia + Hieh-arch palate Cleft palate Long philtrum Shallow + Short neck Widely separated nipples VSD Congenital heart disease Small penis + Cryptorchidism Hydronephrosis Cystic kidneys + + Umbilical hernias Large joint stiffness Equinovarus Equinovalgus Scoliosis Clinodactyly (5th finger) + Abnormal palmar creases Feeding difficulties + Delayed devel+ opment Seizures + Hypotonus Hypertonicity Brain atrophy on CT 3m Age described in 9m case report
q13q15 F 37 w 2.600
q13q15 M Term 3.200
+
Macro
-
Scapho Asym
Dolicho
+
+
+ + +
q13q15 q14q16 F F 40 w 2,420 2,800
+
+ -
-
+
q15q21 M 3,000
q15q21 q15q21 q16q22 M M F 37 w 40 w 1,900 2,550 2,450 -
+ +
+
-
+
+
t
Broad
Flat
+
+
Flat t
-
+ + Flat + -
+ +
CBte Schwartz Young Kueppers Park et Matkins et al. et al. a]. et al. et al et al. 119811 119841 rig851 119881 [I9871 rig771
+
+
+ + Flat -
+ + + + -
-
+
-
-
+ -
+
q16q22 M
q21q22 M
q21q27 M
-
+
+ +
+
-
+
-
-
+ + -
+
+ + PDA
PDA
i
+
i
Almond
i
+
-
+ t
+
Flat
+ +
+
+ + +
+
Flat
+ + + + +
+
+
+ +
+
+
+
+
-
Broad
Promi
+
+
+
Promi i
Small
+
t
-
+
i
-I
i
+ + +
q23q24 M Term 2,600
-
-
Short
q22q23 F
Term 2,720
-
+
+
+
+
+ Kyphosis
+
+
-
+
t -
+
+
i
+
+
+
i
-
+ +
+
+
+
+
+
+
-
-
-
+ +
+
-
i
36 m
13 y
32 m
+
-
24 m
33w death
4m
llm death
+ + +
-
+a
t
+a
2y
12y
+ +
+
-
i
+
13y8 m
15m
+
i
+ + 4y3m
2y
*Fifteen cases, including the present case, with interstitial deletion of6q are presented in the order from proximal to distal deletion. macro, macrocephaly; scapho, scaphocephaly; dolicho, dolichocephaly; asym, asymmetrical; promi, prominent; VSD, ventricular septa1 defect; PDA, patent ductus arteriosus. "Initial hypotonia turned hypertonicity later.
head, hypertelorism, bulbous nose, and malformed ears. They differed on the basis of hypertonicity, antimongoloid slant, and highly arched palate. We reviewed 25 cases of deletion of 6q and found that the breakpoints were widely spread all over the arm. The most common breakpoints were q25 (7 cases), q15 (6 cases), q23 (5 cases), q21(4 cases), and q22 (4 cases). In interstitial deletions q15 and q21 were frequently broken. Cases with proximal deletion (cen-ql5) had some clinical features in common. All of them showed umbilical hernia and delayed development. Short stature, mongoloid slant, short neck, epicanthic folds, and abnor-
mal palmar creases were also found in most of them. On the other hand, patients with distal deletions (q21lq22ter) had no features in common except for delayed development (Table I). In spite of some differences of the phenotype in cases with overlapped deleted portions, this paper could contribute to the delineation of the phenotype of 6q - as a clinical entity. The present case had absent pulmonary valve sequence, a unique type of Tetralogy of Fallot. Although it is a well-recognized entity, there have not been any reports of any type of chromosome abnormality associ-
6q-
ated with it. To our knowledge, the present case is the only case with such a combination.
ACKNOWLEDGMENTS The authors are extremely grateful to Dr. Yasuo Nakagome of the National Children’s Medical Research Center in Tokyo. We also thank the staffs in Special Reference Laboratory in Japan for their initial chromosome analysis.
REFERENCES CBte GB, Papadakou-Lagoyanni C, Metaxotou C (1981) : A de nouo interstitial deletion of band q21 on chromosome 6. Ann Genet (Paris) 24:170-171. Glover G, Lopez I, Gabarr6n J, Carmona JA (1988):Partial monosomy 6q (q15q21) by de nouo interstitial deletion. Clin Genet 33:308-310. ISCN (1985): An international system for human cytogenetic nomenclature (1985)-high resolution banding. Cytogenet Cell Genet 35:48-65. Kueppers F, Dewald G, Gordon H, Pineda A (1977): Exclusion of the HLA locus from a large portion of the long arm chromosome 6. Hum Hered 27:242-246. Lonardo F, Colantuoni M, Festa B, Gentile G, Guerritore G, Perone L,
611
Santulli B, Ventruto V (1988): A malformed girl with a de nouo proximal 6q deletion. Ann Genet (Paris) 31:57-59. Matkins SV, Meyer J E , Berry AC (1987):A child with partial monosomy 6q secondary to a maternal direct insertional event. J Med Genet 23:227-229. McNeal RM, Skoglunt RR, Francke U (1977): Congenital anomalies including the VATER association in a patient with a del(6)q deletion. J Pediatr 91:957-960. Nakagome Y, Tanaka T, Hashimoto T, Kuyama M, Maruyama M (1980): Interstitial deletion 6q in a malformed boy. Ann Genet (Paris) 23:49-51. Park JP, Graham JM, Jr, Berg SZ, Wurster-Hill DH (1988):A de novo interstitial deletion of chromosome 6(q22.2q23.1). Clin Genet 33:65-68. Schwartz MF, Kaffe S, Wallace S, Desnick R J (1984):Interstitial deletion of the long arm of chromosome 6[de1(6) (q16q22)J:Case report and review of the literature. Clin Genet 26:574-578. Slater HR, Robb A, Forsyth LA, Hamilton DA, Clark MC, Galloway CAS (1988): Interstitial deletion (6)(qll+ q15) in an infant with congenital abnormalities. J Med Genet 25:210-211. Turleau C, Demay G, Cabanis MO, Lenoir G, de Grouchy J (1988):6ql monosomy: A distinctive syndrome. Clin Genet 34:38-42. Yamamoto Y, Okamoto N, Shiraishi H, Yanagisawa M, Kamoshita S (1986):Deletion of proximal 6q: A clinical report and review of the literature. Am J Med Genet 25467-471. Young RS, Fidone GS, Reider-Garcia PA, Hansen KL, McCombs JL, Moore CM (1985): Deletion of the long arm of chromosome 6 Two new cases and review of the literature. Am J Med Genet 20:21-29.
